Master in Biomedical Research
2015-2016
List of Potential Laboratories
(alphabetical order using the last name of each principal investigator)
1
Note: a requisite for admission to the Master in Biomedical Research
(BIOMED) is that the student has to be first accepted to do his/her research
practicum in a research laboratory in Barcelona.
A main orientation of the BIOMED master is to continue towards a PhD thesis,
and the majority of students enrolling in this master have, at the time of preregistration, been accepted in research groups to do a PhD after they finish the
master. However, there are students who have a motivation to do this master,
and eventually a PhD, but who may not know how to contact a suitable
laboratory.
This document contains a few guidelines to help candidate students in finding a
research group, and also a list of potential laboratories to which they can submit
applications.
This list is orientative, and students can do their research in another laboratory
that they can find on their own. Also, this list is not just to choose a laboratory:
you must contact the group you are interested in, arrange an interview, and get
the written acceptance of the investigator in charge of that group.
Last, the masters in Clinical Laboratories (BIOLAC) and Pharmaceutical and
Biotechnology Industries of our Department are also valid to continue a PhD
program in research, and they offer the possibility of doing a research-related
practicum. The admission criteria to these masters do not require the previous
acceptance by a research group. We recommend that students who may be
interested in biomedical research-related training, but cannot find a laboratory
for the BIOMED master, might consider enrolling in the BIOLAC or
PHARMA-BIOTECH masters.
2
“How to: getting accepted in a research laboratory”
1‐ You have to know what you would like to work on. 2‐ Be specific: you should be able to say what are the questions that are important to you and why.
Not very good: I want to work in neurosciences, I have always liked it.
Much better: I want to understand the processes and mechanisms that make neurons more sensitive to oxidative stress and oxygen deprivation in patients with neurodegenerative diseases such as...
Not very good: I want to work in regenerative medicine, I think that stem cells have a lot of potential to cure diseases.
Much better: I want to contribute to the identification of proteins that when expressed in a differentiated cell such as a hb
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fibroblast, can cause it to dedifferentiate and acquire functional characteristics of a pluripotent cell. 3‐ Find out who is working on what.
Websites of universities and research centers, PubMed searches, Google...
It takes time! (don’t wait till last minute to begin looking for your favorite lab)
4‐ Write to the group that interests you.
5‐ Contacting a group.
a) Motivation letter: tell them why you want to work with them (for this, you need to know something about what they do and about current questions in the field). It takes time! (don’t wait till last minute to begin looking for your favorite lab)
Also tell them why you are good. Labs appreciate commitment, responsibility, ability to work in a team, ability to persevere and
a strong motivation. Ask them for an interview to show them how good you are. Do not write a generic letter to copy paste and send to ten different laboratories changing only the name of the group leader
Do not write a generic letter to copy‐paste and send to ten different laboratories changing only the name of the group leader. Choose your labs and send a personal, specific letter to each one. b) Keep in mind that a person working full time in a cellular‐molecular biology lab can spend more than 1000 euros/month in materials, besides a lot of time required to train you and supervise you until you begin to get solid results. Expect that during the first 6 months it is more likely that you will produce more trouble and expenses than productive results.
Laboratories are usually not financed by the university nor the research center, and they get the money from competitive grants that are given or denied based on publication in internationally respected journals.
Do not get discouraged with rejections, learn from them to improve your application.
c) Do not forget important details in your CV:
p
1‐ Give names of senior persons that can be a reference. Be careful with “clone” reference letters from teachers that don’t really know you and will just say general things. 2‐ Include your university scores. If they are not too good, you should be ready to explain why, either in your application letter or in an interview. Be honest and realistic about it. If the teaching/exam system of your university hasn’t worked for you, you will know the reasons better than anyone else, so be prepared to speak frankly about it. University scores are not an exact indicator of who will become a successful scientist but they say that a person has gone
University scores are not an exact indicator of who will become a successful scientist, but they say that a person has gone through 4‐5 years of serious effort with a better than average performance.
Most people will interpret this as a sign of self‐discipline, organization, capacity to work even if you have a bad day, and to get things done regardless of whether they are more fun or plainly boring.
Please notice that on April the 24th, four new projects have been added at the
beginning of this list.
1
Project Title: Translational
research in cancer
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Ana Rovira Guerín, PhD
Molecular Therapeutics in Cancer (Responsable Preclinical Laboratory). Cancer
Research Program, IMIM. Barcelona Biomedical Research Park, PRBB (office 168).
Doctor Aiguader, 88, 08003 BCN. Tel. 93 316 0596; e-mail: arovira@imim.es
Summary of project summary or current research lines (less than 300 words).
Our goal is improving the treatment of human cancer through preclinical research with
novel anticancer agents/combinations in cell culture, in vivo models, and biomarker
studies in preclinical and clinical settings. This research should ultimately serve as
basis for clinical trial design and patient selection towards individualized medicine. We
focus on translational projects in breast, colon, lung, and bladder cancer. State-of-the
art techniques for in vitro and in vivo studies are being used and we validate the results
in a cohort of patients. For that, clinical specimens are being interrogated by up-to-date
-omics (mainly NGS and transcriptomics) or by conventional, clinically used,
technologies (IHC, FISH, sequencing). The group is led by Dr. Joan Albanell, Director
of the Medical Oncology Service at the Hospital del Mar and Director of the Cancer
Research Program at IMIM. The group is comprised of oncologists, pathologists and
biologists and is a Consolidated Research Group by the Generalitat de Catalunya and
member of the Spanish Network for Cooperative Research in Cancer. Selected
Publications (2015-2012): PMID: 25623215; PMID: 25128455; PMID: 24284055 and
PMID: 22270724.
General outline of current projects focused on breast cancer
Women with HER2 positive subtype of breast cancer are treated with monoclonal
antibodies against the HER2 that have improved the outcome of the patients. However,
they are not curative; resistance to anti-HER2 inevitably occurs. Over 50% of these
patients will develop brain metastasis. There is a need to find predictors of resistance
as well as novel strategies to prevent or reverse resistance. Two projects are being
developed in this field:
1. Identification of resistance mechanisms to novel anti-HER2 antibodies in
breast cancer (IP: Joan Albanell).
The objective is to identify resistance mechanisms anti-HER2 antibodies in breast
cancer as well as to provide novel targets to be explored in translational and clinical
studies. Our experimental approach is based on the generation of cell lines resistant to
anti-HER2 antibodies and, in parallel, on the collection of serial tumor and blood
samples from patients treated with these antibodies.
2. Identification of specific molecular mediators for HER2 positive breast cancer
brain metastasis (IP: María Martinez).
The objective is to identify molecular mechanisms related to brain metastasis
development in HER2 positive patients, in order to identify possible new therapeutic
therapies, as well as identification of biomarkers that predict the risk for central nervous
system dissemination in this population. This is a collaborative study with Dr. Gomis
(IRB), an internationally recognized leader in the study of organ-specific metastasis.
The experimental approach is based on the generation of HER2 positive cell lines with
high affinity to develop brain metastasis (by using in vitro models of the blood-brainbarrier (BBB)) and to confirm these effects in animal models.
2
Project Title: How do sensory neurons of the inner ear migrate out the epithelium?
Project supervisor
Berta Alsina
Associate Professor
Berta.alsina@upf.edu
Dr.Aiguader 88, 08003 Barcelona
Laboratory of Developmental Biology
Universitat Pompeu Fabra-PRBB
http://lavandula.imim.es/Alsina_Group/
Summary of project summary or current research lines (less than 300 words).
We have focused for several years now on how neurogenesis takes place in the inner
ear. Recently we have been setting the conditions for high spatial and temporal
resolution imaging of the process in vivo. We can visualize in real time the cellular
events leading the migration of sensory neurons out of the epithelium. We have seen
that neuronal progenitors expressing neurogenin1 lose the attachment to the apical
membrane, are squeezed by its neighbours and display dynamic and very fast cellular
protrusions before exiting. Some of the events and molecular markers identified are
similar to the epithelial-mesenchymal transition (EMT) process that leads cancerous
cells to exit an epithelium and metastasize. Therefore, it is highly relevant to
understand at high resolution how this process occurs. We aim to investigate the
mechanisms underlying neuronal remodelling by asking: are cellular shape changes
controlled by F-actin and myosin II, which are the cell-adhesion changes that allow the
sensory neuron migration, which upstream signalling molecule triggers the cellular
events, are neurons exiting the epithelium by an EMT process and are they following a
chemotaxis signal? In order to address these questions we will use genetic and
pharmacological perturbations of zebrafish embryos, combined with high resolution in
vivo confocal microscopy. The laboratory already has several transgenic zebrafish lines
that label sensory neurons. The student will learn to inject mRNAs to zebrafish
embryos, manipulate the embryos pharmacologically, in situ hybridization techniques
for gene expression analysis and perform in vivo time-lapse imaging by confocal
microscopy.
3
Project Title: (1) Noise and feedback loops in gene expression.
(2) Adaptive mechanisms behind variation in RNA polymerase
fidelity.
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Lucas Carey. Group Leader, Single Cell Behavior.
<lucas.carey@upf.edu> . 933160903 , Room 325. Carrer del
Doctor Aiguader, 88, 08003 Barcelona
http://www.upf.edu/scb/
Summary of project summary or current research lines (less than 300 words).
There are two on-going projects which can be joined. In addition, a suitably motivated
and hard working student is free to develop his/her own project.
(1) Gene expression is noisy. We have two on-going experimental projects to
understand the way in which various molecular mechanisms, such as DNA
supercoiling and feedback loops affect the noise in gene expression. This is a
mostly experimental project.
(2) We have developed a new computational technique for measuring RNA
polymerase fidelity using RNA-seq data. We use a combination of experimental
data from yeast generated in our lab, and publically available RNA-seq data
from humans and other species, to understand the mechanisms by which cells
can regulate RNA polymerase fidelity, and the role that changes in fidelity play
in cancer and other diseases. This is a mostly computational project, and
requires programming experience.
4
Project Title: Epigenetic profile of dysferlin locus in monocytes and muscle cells
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Mònica Suelves Esteban, PhD
Associate Investigator
Institute of Predictive and Personalized Medicine of Cancer (IMPPC)
Crta de Can Ruti, camí de les escoles s/n
08916 Badalona-Barcelona-Spain
Phone: 93-5545058
Fax: 93-4651472
msuelves@imppc.org
Summary of project summary or current research lines (less than 300 words).
Epigenetic regulation is key to establish the cellular identity. In addition, epigenetic
alterations have profound effects on many pathologies, since histone modifications and
DNA methylation influence gene expression. In the laboratory, we are analyzing the
dynamics of the histone modification profiles and DNA methylation patterns during the
myogenic differentiation process using in vitro and ex-vivo cellular models. Recently,
we have begun a collaborative project with Dr. Gallardo (St Pau Hospital) to analyze
the epigenetic profile of the dysferlin locus on monocytes and muscle cells. Dysferlin is
a protein involved in muscle differentiation and regeneration and DYSF gene it is found
mutated in patients affected by dysferlinopathies. Recently, it has been reported the
existence of two transcription start sites (TSSs) leading the expression of two different
isoforms. The aim of the project is to characterize the epigenetic landscape of both
TSSs in human cells, performing chromatin inmunoprecipitation assays (ChIPs) for
analyzing histone marks, and bisulfite sequencing to analyze DNA methylation
patterns.
5
Project Title:
Molecular mechanisms controlling cell size and cell cycle during stress
imposition.
Project supervisor:
José Ayté
Universitat Pompeu Fabra
C/ Dr.Aiguader 88
08003 Barcelona
Tel. 34-93-316-0848
Fax. 34-93-316-0901
jose.ayte@upf.edu
Summary of current research lines.
Our group is interested in studying the components and molecular mechanisms
which regulate the responses to oxidative stress and the control of the cell
cycle, using the fission yeast Schizosaccharomyces pombe as a model
system. To obtain more information about the laboratory and about our
research interests, please consult our group’s web page (www.upf.edu/osccg).
Some recent publications of the group include:
García-Santamarina et al. 2014. Nature Protocols 9(5):1131.
García et al. 2014. Nucleic Acids Res. 42:10351.
Calvo, I.A. et al. 2013. Cell Reports 5:1413.
Ivanova, T. et al. 2013. Mol. Biol. Cell 24:3350.
Fernández-Vázquez et al. 2013. PLoS Genet. 9:e1003647.
Calvo, I.A. et al. 2012. Nucleic Acids Res. 40:4816.
Gómez-Escoda et al. 2011. EMBO Rep. 12:84.
Zuin, A. et al. 2010. EMBO J. 29:981.
Moldón et al. 2008. Nature 455:997.
The stress-related MAP kinase displays a cdc elongated phenotype, and we
have isolated unexpected suppressors of this phenotype. The aim of this master
project will be to elucidate the molecular bases of the suppressor mutations.
6
Project Title: Stroma remodelling during cancer malignance
Project supervisor
Josep Baulida, PhD
Programa de Recerca en Càncer
IMIM-Institut Hospital del Mar d’Investigacions Mèdiques
Parc de Recerca Biomèdica de Barcelona
c/Doctor Aiguader, 88
08003 Barcelona, Spain
Mailto: jbaulida@imim.es
Tel 93 3160436
http://www.imim.es/programesrecerca/cancer/en_elementsinvolved.html
Summary of project or current research lines
We have described that at diagnosis, 16% of the early infiltrating breast cancers
present Cancer–Associated Fibroblast (CAF) expressing the transcription factor Snail1.
These patients have a worse prognosis than those presenting Snail1 negative
fibroblasts.
CAFs are healthy cells activated by tumors that are embedded into the connective
tissue surrounding the tumor mass. We have demonstrated that Snail1-expressing
CAFs generate a pro-metastatic micro-environment around tumors: the extracellular
fibers, such as the fibonectin and collagen fibers, are aligned and the rigidity of the
connective tissue is locally higher than that of unaffected tissues.
The master project aims to study how CAFs expressing Snail1 facilities cancer
malignance and how their activity can be inhibited.
We propose a molecular approach to unveil new pharmacological targetable molecules
on CAFs. Cell culture, biochemichal techniques and genetically modified mouse
models for cancer will be used.
Tridimensional reconstruction of a prometastatic extracellular matrix.
From confocal immuno-fluorescent images of
activated fibroblasts in culture.
Extracellular fibronectin fibers in red,
intracellular αSMA-stress fibers in green and
nuclei (DAPI) in blue.
Snail1-expressing CAFs remodel the extracellular matrix, which, in turn,
promotes Snail1 expression. Fibronectin fibers are in pink, Collagen fibers in violet
and αSMA-stress fibers in green. Focal adhesions are in red.
7
Project Title: Time, Space and Energy in Hormone Regulated Gene Expression
Project supervisor
Miguel Beato, Senior Group Leader, miguel.beato@crg.eu
Tlf +34 93 316 0119
Secretary: Magali Bartomeus, e-mail: magali.bartomeus@crg.eu
Tlf +34 93 316 0161
CRG, Dr. Aiguder, 88
08003 Barcelona, Spain
Summary of project summary or current research lines.
We use the response of breast cancer cells to the steroid hormone progesterone (Pg) to
decipher the molecular mechanisms of transcriptional reprograming. We found that the
organization in nucleosomes of the DNA sequences recognized by the progesterone
receptor (PR) is key for chromatin remodeling that depends on PR associated enzymatic
activities, including kinases, histone modifying enzymes, ATP-dependent remodelers
and PARP1 2-5.
We also found that the conserved division of the genome in consecutive
topological associating domains (TADs) contributes to coordination of the hormonal
response, as the regulated genes segregate significantly into TADs that respond as a
whole with either activation or repression of transcription 6. In response to hormone
repressed TADs compact, loose short-distance and gain long-distance interactions,
while activated TADs expand by gaining medium-distance and loosing long-distance
interactions 6.
The extensive remodeling of chromatin in response to hormones requires a large
amount of ATP to feed the ATPases at the heart of the remodeling complexes. We
found that this ATP is mainly generated in the cell nucleus by NUDIX5, which uses
ADP-Ribose (ADPR) coming from PARG-mediated hydrolysis of PAR 7. Depleting
NUDIX5 compromises chromatin remodeling and cell proliferation in response to
hormone 7. NUDIX5 and other enzymes of the pathway are overexpressed in breast
cancers and are marker for poor prognosis.
Future plans center in understanding the relationship between the 3D genome
structure, chromatin dynamics and the transcriptional response to Pg, which eventually
leads to changes in cell fate in the direction of cancer stem cells. Apart from genome
editing, the main techniques employed will super-resolution microscopy, single cell
genomics, and Hi-C analysis of chromosomal interactions and modelling.
References:
1
Ballare C et al (2013) Mol Cell 49, 67-79; 2 Vicent GP et al (2006) Mol Cell 24,
367-81; 3 Vicent GP et al (2009) PLoS Genet 5, e1000567; 4 Vicent GP et al (2011)
Genes Dev 25, 845-62; 5 Wright RHG et al (2012) Genes Dev 26, 1972-83; 6 Le
Dily F et al (2014) Genes Dev 28, 2151-62; 7 Wright RHG et al (2014) BioRxiv
doi:10.1101/006593
8
Project Title: Study of the neurobiological mechanisms involved in drug dependence,
and the consolidation and extinction of aversive memories
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Dr. Fernando Berrendero Díaz
Associate Professor (UPF)
Laboratory of Neuropharmacology
Department of Experimental and Health Sciences
University Pompeu Fabra (UPF)
Barcelona Biomedical Research Park (PRBB)
c/ Dr. Aiguader, 88
08003 Barcelona, Spain
Phone: 93 3160890
E-mail: fernando.berrendero@upf.edu
Summary of project summary or current research lines (less than 300 words).
Current research lines
- Involvement of the hypocretin/orexin system in the addictive properties of
cannabinoids
- Neurobiological mechanisms involved in the cognitive deficits associated with the
nicotine withdrawal syndrome
- Role of the endogenous cannabinoid system in the addictive properties of nicotine
- Role of the hypocretin/orexin system in the consolidation and extinction of fear
memories
9
Project Title:
Inhibition of the SAPK pathways by nuclear receptors: mechanisms and actions
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Carme Caelles, PhD
Associate Professor
Cell Signaling Research Group
Department of Biochemistry & Molecular Biology
School of Pharmacy
University of Barcelona
Av. Diagonal, 643; Edifici B, 1ª planta
08028-Barcelona
Phone: 93-4037130
E-mail: ccaelles@ub.edu
Summary of project summary or current research lines (less than 300 words).
Carme Caelles’ lab studies the principles that govern cross talk between some of the
cell’s most relevant signalling pathways in the context of important pharmacological
actions such as anti-inflammatory, anti-proliferative and anti-diabetic actions. Their
research efforts are directed to gaining a better understanding of the molecular
mechanisms underlying the pharmacological activities of molecules, which are ligands
for a particular set of nuclear receptors, in particular the glucocorticoid receptor (GR),
the peroxisome-proliferator activated receptors (PPARs) and liver X receptors (LXRs).
All these molecules, acting through their specific receptors, share in common the ability
to inhibit the activation of the stress-activated protein kinase (SAPKs) pathways,
namely JNK and p38MAPK cascades, well-known mediators of pro-inflammatory
signalling. For instance, blockage of SAPK activation is crucial not only for the antiinflammatory action of these molecules, but also for other relevant pharmacological
actions, such as for the anti-diabetic action of the PPAR ligands thiazolidinediones
(TZDs).
In vivo JNK activation in pancreatic β-cells leads to glucose intolerance caused by
insulin resistance in pancreas. Lanuza-Masdeu J, Arévalo MI, Vila C, Barberà A, Gomis
R, Caelles C. Diabetes. (2013) 62:2308-17.
Hypoglycemic action of thiazolidinediones/peroxisome proliferator-activated receptor
gamma by inhibition of the c-Jun NH2-terminal kinase pathway. Díaz-Delfín J, Morales
M, Caelles C. Diabetes. (2007) 56:1865-71.
Glucocorticoid receptor-JNK interaction mediates inhibition of the JNK pathway by
glucocorticoids. Bruna A, Nicolàs M, Muñoz A, Kyriakis JM, Caelles C. EMBO J.
(2003) 22:6035-44.
10
Project Title: Molecular and Genetic control of adult differentiation
Project supervisors Elena Casacuberta, Xavier Franch-Marro and David Martín
Casacuberta
CSIC Scientists
Institute of Evolutionary Biology IBE (CSIC-UPF)
elena.casacuberta@ibe.upf-csic.es, xavier.franch@ibe.upf-csic.es,
david.martin@ibe.upf-csic.es
Our group is the result of joining three different research groups to combine expertise
in order to investigate with a wide variety of techniques and knowledge our current line
of research. Our fusion has allowed the investigations to take place in three different
animals models simultaneously, the insects Drosophila melanogaster, Tribolium
castaneum and Blattella germanica. The student that will joined the group will have the
opportunity to interact with a variety of scientist at different points of their career which
of them with a different technical skills.
A project for a Master student could be in any of the on going investigations. Our
projects involve the use of insect genetics, molecular and cellular biology, biochemistry
and fluoresence and confocal microscopy.
Summary:
All immature animals undergo remarkable morphological and physiological changes to
become mature adults. In winged insects, metamorphic changes are either limited to a
few tissues (hemimetaboly) or involve a complete reorganization of most tissues and
organs (holometaboly). Despite the significant differences between hemimetaboly and
holometaboly, two hormones, the steroid ecdysone and the juvenile hormone control
both types of insect metamorphosis by changing the responsiveness of metamorphic
tissues to a number of signaling pathways (mainly Hh, EGF, Notch, Dpp, and Wnt).
Remarkably, the same hormonal and signaling pathways are also used to pattern the
juvenile forms of both types of insects suggesting that other stage-specific factors
modify the specific responsiveness of target genes during the last metamorphic
transition.
In this regard, our group has recently identified the transcription factor E93 as the key
factor that promotes adult metamorphosis in both hemimetabolous and holometabolous
insects, hence acting as the universal adult specifier. To approach this question we
propose a multidisciplinary approach aiming to tackle the following points: (1) how is
regulated the highly restricted expression of E93, (2) the relationship between E93
expression and telomere length, (3) the characterization of the entire set of target
genes of E93 during the metamorphic stage, (4) the characterization of the molecular
mode of action of E93 and, (5) the analysis of the evolutionary implication of E93 in the
origin of holometabolan metamorphosis. In addition, we also plan to determine the role
of Ligand Co-Repressor (LCoR), the vertebrate ortholog of E93, in adult vertebrate
maturation.
In summary our multidisciplinary project aims to gain insight into the molecular
mechanisms that controls the transition from the juvenile to the adult form, a key event
in higher organisms. Our results will also generate the basic knowledge to generate
molecules that eventually would serve as insecticides as well as human treatments to
the more frequent problems associated to deregulated puberty
11
Project Title: Vitamin D levels during pregnancy and child neuropsychological
development: a Mendelian Randomization approach
Project supervisors (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Maribel Casas, PhD at CREAL, mcasas@creal.cat, 932147364
Background in environmental epidemiology and main interest on the effects of
exposure to environmental chemicals and maternal obesity during pregnancy and early
childhood
Mariona Bustamante, PhD at CREAL and CRG, mbustamante@creal.cat, 933160197
Background in human genetics and main interests in genetics of complex traits and
epigenetics as a potential link between exposures and health outcomes
Summary of project summary or current research lines (less than 300 words).
Several maternal traits have been associated with child health outcomes. In the INMA
Project (Childhood and Environment, http://www.proyectoinma.org/), we found that high
levels of circulating vitamin D during pregnancy were associated with better infant
neuropsychological development (Morales et al. 2012). However these associations
might be confounded by other factors.
To address causality, we aim to use a Mendelian randomization approach in the
context of EGG-mothers consortium (Early Growth Genetics, http://eggconsortium.org/). Mendelian randomization is a method of using measured variation in
genes of known function to examine the causal effect of a particular exposure on
disease in non-experimental studies. Genetic scores (additive combination of risk
alleles from different SNPs) are more powerful than individual SNPs in this type of
analysis.
The proposed tasks are:
‐ To create maternal vitamin D genetic score taking into account missing
genotypes and weighting them according to the literature in INMA cohort.
‐ To analyze the association between the genetic score and vitamin D levels in
INMA cohort.
‐ To analyze the association between the genetic score and child
neuropsychological development to infer causality in INMA cohort.
‐ To harmonize the cognition and ADHD traits among participating cohorts in the
EGG consortium.
‐ To run a meta-analysis of the Mendelian Randomization results from different
child cohorts in EGG.
12
Project Title: Antioxidant diet during pregnancy and placental mtDNA content, a
biomarker of oxidative stress
Project supervisors (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Maribel Casas, PhD, Postdoctoral researcher, mcasas@creal.cat, 932147364. Centre
for Research in Environmental Epidemiology (CREAL). Doctor Aiguader, 88 08003,
Barcelona, www.creal.cat
Martine Vrijheid, PhD, Professor, mvrijheid@creal.cat, 932147346. Centre for
Research in Environmental Epidemiology (CREAL). Doctor Aiguader, 88 08003,
Barcelona, www.creal.cat
Summary of project summary or current research lines (less than 300 words).
Oxidative stress reflects an imbalance between the systemic manifestation of reactive
oxygen species and a biological system's ability to detoxify the reactive intermediates
or to repair the resulting damage. In humans, oxidative stress is thought to be involved
in the development of different health effects such as cancer, neurodegenerative and
cardiovascular diseases, and autism. During pregnancy, oxidative stress have been
associated with low birth weight, type 2 diabetes, and preeclampsia. Thus, oxidative
stress during pregnancy may be a connecting link between intrauterine insult and
programming consequences after birth. Mitochondria are intracellular organelles that
are essential for the aerobic production of adenosine triphosphate (ATP) but they are
also the primary targets of oxidative stress. In comparison with nuclear DNA,
mitochondrial DNA (mtDNA) is lacking the protective strategies associated with nuclear
DNA, such as protective histones, chromatine structure, and sufficient DNA repair
capacity. Consequently, mtDNA is particularly vulnerable to ROS-induced damage and
has a high mutation rate. Mitochondria compensate for these mutations by increasing
the number of mitochondria and by replicating mtDNA, resulting in a change in mtDNA
content, which therefore reflects mitochondrial damage and dysfunction.
Dietary antioxidants may play a role in counterbalancing the oxidative stress during
pregnancy and subsequently reducing its potential perinatal health effects. INMA
(Infancia y Medio Ambiente - Childhood and Environment) is a population-based birth
cohort established in several Spanish regions with the aim to study the paper of the
more relevant environmental pollutants in the air, water and diet during the pregnancy
and beginning of life, and their effects in the growth and development. In INMA we
have collected dietary information in the 1st and 3rd trimesters of pregnancy by means
of a food-frequency questionnaire and measured mtDNA content in placenta at birth.
The student will evaluate whether an antioxidant diet during pregnancy is associated
with mtDNA, as a marker of oxidative stress.
13
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Dr Julián Cerón Madrigal
Cancer and Human Molecular Genetics Area
Hospital Duran i Reynals (Hospital Oncológico) 3a planta - Gran Via de l'Hospitalet,
199. 08908 L'Hospitalet de Llobregat. Barcelona – Spain
jceron@idibell.cat
www.gusano.info/ceronlab
Summary of project summary or current research lines (less than 300 words).
We work with a model organism, the nematode Caenorhabditis elegans that is
widely used in biomedical research. Scientists working with this model have been
awarded with three Nobel prizes, including two Nobel prizes in Medicine and
Physiology.
Our laboratory is located within a hospital and therefore it is an extraordinary
environment to develop translational project oriented to human diseases.
There are two main research lines ongoing in our lab: (i) The first intends to identify
genes that provide resistance or sensitivity to chemotherapeutic agents such as
Cisplatin. (ii) The second explore the functional role of genes regulating splicing whose
human homologs are involved in diseases.
A typical master project in our lab include many techniques as manipulation and
maintenance of C. elegans, purification of DNA and RNA, molecular cloning to
construct transgenes, generation of transgenic animals and mutant strains, RNAi
experiments, Immunofluorescence, microscopy, Real-Time PCR, analysis and
validation of RNA-seq data..etc..
We are having lab meetings every week and the official language for these meetings is
English.
14
Project Title: Cholesterol in amyloid beta clearance as a therapeutic target in
Alzheimer’s disease
Project supervisor
Dr. Anna Colell Riera
Cientifico Titular CSIC
anna.colell@iibb.csic.es
Department of Cell Death and Proliferation
Institute of Biomedical Research of Barcelona (IIBB)
Spanish National Research Council (CSIC)
Centro Esther Koplowitz
Roselló 153, 4th floor
08036-Barcelona. Spain
Tel. : +34 93 227 54 00 ext.4021
FAX: +34 93 363 83 01
www.iibb.csic.es
https://scholar.google.es/citations?hl=es&user=TfiuS4MAAAAJ&view_op=list_works&sortby=pu
bdate
Summary of project summary or current research lines (less than 300 words).
Background:
Recent studies suggest defective amyloid beta (Ab) clearance as the driving force
behind sporadic Alzheimer’s disease (AD); however, the specific factors that promote
their impairment still remain to be fully defined. Increased cholesterol has been linked
to amyloidogenesis, but sterols could also regulate Ab disposal by altering different
cellular degradative systems including autophagy. Furthermore, studies from our
laboratory show that cholesterol accumulation in mitochondria accelerates AD-like
symptoms via lowering mitochondrial glutathione (mGSH) levels and enhancing Abinduced oxidative stress. Interestingly, oxidative inactivation of Ab-degrading enzymes
and impairment of microglia phagocytosis by ROS have been recently described. Base
on these data, we hypothesize that mitochondrial cholesterol as a contributory factor of
defective Ab clearance may become a key target for therapeutic interventions. In vivo
studies using APP/PS1 mice ± SREBP-2 overexpression treated with cholesterol/GSHmodifying agents as well as cellular and molecular tools will be used to address the
specific aims.
Specific aims:
Aim 1. High cholesterol and endolysosomal/autophagy dysfunction. First, we will
evaluate cholesterol effect on several markers of lysosomal function and integrity.
Impairment of lysosomal fusion capability and autophagy flux will be also addressed.
To analyze the contribution of these alterations on Ab catabolism, we will assess levels
of Ab in lysosomes, plaque load and the reversal effect of an in vivo therapy using
cholesterol-lowering agents ± lysosome inhibitors.
Aim 2. Cholesterol impact on Ab proteolysis and phagocytosis. We will determine
levels and activity changes of the two major Ab-degrading enzymes, namely neprilysin
(NEP) and insulin-degrading enzyme (IDE) induced by cholesterol. We will test whether
mGSH content can regulate NEP/IDE activities and Ab levels. The effect of cholesterolinduced mGSH depletion on NLRP3 inflammasome and microglial phagocytosis will be
analyzed, and the benefitial effect of GSH ethyl esther treatment will be tested.
15
Project Title: Structural characterization of DNA-binding proteins and complexes by
crystallography and X-ray diffraction
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Prof. Miquel Coll i Capella
Institut de Recerca Biomèdica
& Institut de Biologia Molecular de Barcelona (CSIC)
Parc Científic de Barcelona
Josep Samitier 1-5
08028 Barcelona
Spain
Tel. 34 93 4034951
Fax 34 93 4034979
Email miquel.coll@irbbarcelona.org
URL www.irbbarcelona.org/mcoll
www.ibmb.csic.es
Summary of project summary or current research lines (less than 300 words).
Our group is devoted to the structural analysis, by X-ray diffraction, of several DNA-binding
proteins and complexes. These proteins play key roles in different biological processes such as
DNA translocation, replication and transcription. In our lab, we crystallize most of these proteins
in complex with their DNA targets in order to understand, at the molecular level, their function.
The UPF Master Student will participate in the cloning, expression, purification or crystallization of
one of these proteins or protein-DNA complexes, with the final goal of their structural
characterization using X-ray diffraction.
16
Project Title: Epigenetic regulation of gene expression in malaria parasites
Project supervisor:
Alfred Cortés
ICREA Research Professor
Barcelona Centre for International Health Research (CRESIB)
C./ Rosselló 153, 1st floor (CEK building)
08036 Barcelona, Catalonia, Spain
Tel. +34 93 2275400 ext. 4519
alfred.cortes@cresib.cat
http://www.icrea.cat/Web/ScientificStaff/Alfred-Cortes-Closas-375
Summary of current research lines:
Two cells with identical genomes can have dramatically different phenotypes. If the differences are
transmissible from one generation to the next, the differences are considered epigenetic. Our lab
investigates how malaria parasites adapt to changes in their environment using spontaneous
transcriptional variation controlled at the epigenetic level. We have recently demonstrated a role for
transcriptional variation in the adaptation of malaria parasites to drug resistance and to heat shock
mimicking malarial fevers. More recently we identified a gene regulated at the epigenetic level that
operates as a switch for sexual conversion. Importantly, sexual stages of the parasite are essential for
transmission from humans to mosquitoes. We also study the chromatin-based epigenetic
mechanisms that regulate these processes in malaria parasites.
For our research we routinely use malaria parasite cultures, transcriptional analysis (by quantitative
PCR and by microarrays), chromatin immunoprecipitation (ChIP), and generation of transgenic
parasite lines, among many other techniques. We collaborate with groups in Europe, USA and
Singapore. We do basic research, but our investigations focus on aspects of parasite biology of great
relevance in the fight against malaria.
Relevant recent publications from our group:
1. Kafsack, B.F.C., Rovira-Graells, N., Clark, T.G., Bancells, C., Crowley, V.M., Campino, S.G., Williams,
A.E., Drought, L.G., Kwiatkowski, D.P., Baker, D.A., Cortés, A. & Llinás, M., 2014, "A transcriptional switch
underlies commitment to sexual development in malaria parasites", Nature 507:248-52.
2. Mira-Martínez, S., Rovira-Graells, N., Crowley, V.M., Altenhofen, L.M., Llinás, M. & Cortés, A., 2013,
“Epigenetic switches in clag3 genes mediate blasticidin S resistance in malaria parasites”, Cell. Microbiol.
15:1913‐23.
3. Cortés, A., Crowley, V.M., Vaquero, A. & Voss, T.S., 2012, “A View on the Role of Epigenetics in the
Biology of Malaria Parasites”, PLoS Pathog. 8: e1002943.
4. Rovira-Graells, N., Gupta, A.P., Planet, E., Crowley, V.M., Mok, S., Ribas de Pouplana, L., Preiser, P.R.,
Bozdech, Z. & Cortés, A., 2012, “Transcriptional variation in the malaria parasite Plasmodium falciparum”,
Genome Res., 22:925-38.
Selected as a May 2012 highlight in Nature Reviews Genetics (Casci, T., 2012, “Adaptation: Malarial bet hedging”, Nat.
Rev. Genet. 13:298-9).
5. Crowley, V.M., Rovira-Graells, N., Ribas de Pouplana, L. & Cortés, A., 2011, “Heterochromatin
Formation in Bistable Chromatin Domains Controls the Epigenetic Repression of Clonally Variant
Plasmodium falciparum Genes Linked to Erythrocyte Invasion”. Mol. Microbiol. 80:391-406.
17
Title: Green Spaces and Biomarkers of Systemic Inflammation
Project supervisor
Dr. Payam Dadvand, Associate Research Professor (Ramon y Cajal holder)
(pdadvand@creal.cat, 93 214 73 29, Centre for Research in Environmental
Epidemiology- PRBB, C. Doctor Aiguader 88, 08003 Barcelona, Spain, www.creal.cat )
Dr. Stefano Guerra, Associate Research Professor (sguerra@creal.cat, 93 214 73 58,
Centre for Research in Environmental Epidemiology- PRBB, C. Doctor Aiguader 88,
08003 Barcelona, Spain, www.creal.cat )
Description: Half of the world population is currently living in cities and it is
projected that by 2030 about 70% of the world population will live in urban
areas. Such rapid urbanization has raised concerns regarding health
implications of living in urban areas where people often have limited exposure
to green spaces. An emerging body of evidence has associated exposure
greenness with improve both physical and mental health and well-being;
however, little is known about the potential mechanisms underlying such
benefits. We hypothesize that amelioration of systemic inflammation can be a
potential mechanism underlying the health benefits of greenness exposure.
Accordingly this project will aim to investigate the association between
greenness exposure and biomarkers of systemic inflammation, using data
obtained in the context of the Spanish part of the European Community
Respiratory Health Survey (ECRHS: http://www.ecrhs.org/ECRHS%20II.htm ).
ECRHS I was initiated in 1991-93 with the main objective of estimating
variation in the prevalence of asthma, asthma-like symptoms, asthma
sensitization and bronchial reactivity, and variation in exposure to risk factors
and treatment for these conditions across Europe. It included 15,716
participants aged 20-44 years selected at random from available populationbased registers in 45 centres in 25 countries. A follow-up project, ECRHS II,
was conducted between 1998 and 2002 to determine the incidence and
prognosis of asthma, allergic conditions, and poor lung function in adults, and
to identify their environmental risk factors and susceptible subgroups within
the populations. ECRHS II consisted of 29 centres in which ECRHS I
participants were sent a short screening questionnaire. Those who responded
(65.3%) were invited to participate in the study. The current project will
make use of available data on biomarker levels obtained in ECRHS-II. This
study, for the first time, will report on the impact of green spaces on systemic
inflammation using biomarker data and will advance our knowledge regarding
health effects of greenness exposure.
18
Project Title
Neural Stem Cell Factors as Main Players in the Pathogenesis of Glioblastoma
Project supervisor
Núria de la Iglesia Zaragoza, Ph.D.
Principal Investigator
Glioma and Neural Stem Cell Group
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
e-mail: niglesia@clinic.ub.es
tel.: (+34) 932275400 Ext.4792
address:
Centre Esther Koplowitz (CEK) - Planta 2
C/Rosselló, 149-153. 08036 – Barcelona, Spain
web page:
http://www.idibaps.org/research/709/clinical-and-experimental-neuroimmunology
Project summary and current research lines
Our research group is a young, highly motivated team devoted to applying developmental
neurobiology principles to the study of glioblastoma, one of the most aggressive human
tumors. Glioblastomas arise from a rare subpopulation of cells which have stem-like properties
such as self-renewal, multipotency and the ability to initiate a tumor upon serial
transplantation. These so-called glioma initiating cells (GIC) share specific properties with
neural stem cells (NSC), including the localization to specialized microenvironments within the
brain that support their maintenance. This suggests that factors involved in NSC biology are
likely to contribute to the pathogenesis of gliomas.
To identify new candidates involved in NSC/GIC biology, we integrate our previous
knowledge on developmental neurobiology and adult NSC biology together with bioinformatic
analyses of cancer genome datasets such as TCGA. Our projects are highly multidisciplinary
and involve the use of molecular biology, cell biology, and mouse modeling approaches to
address fundamental questions relevant to NSC and cancer biology.
Main research lines:
Study of NSC factors in the context of glioblastoma pathogenesis.
Characterization of the immunological properties of glioma initiating cells (GIC).
Design of novel therapies targeting GIC.
Dr. de la Iglesia was trained as a posdoctoral fellow in the molecular neurobiology
laboratory of Dr. Azad Bonni at Harvard Medical School. She is now the group leader at the
Glioma and Neural Stem Cell group at Institut d’Investigacions Biomèdiques August Pi i
Sunyer (IDIBAPS). IDIBAPS is in the midst of the Hospital Clinic-Faculty of Medicine complex,
which provides an extremely favourable environment for research in the biomedical field.
Indeed, we work in close relationship with the Medical Oncology department at Hospital Clínic
de Barcelona with the ultimate goal to translate our research from bench to bedside
19
Project Title: Modulation of endogenous hydroxytyrosol formation from dietary tyrosol
by CYP2A6 genetic polymorphism in humans.
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Rafael de la Torre Fornell, PharmD, PhD
IMIM (Hospital del Mar Medical Research Institute)
Co-ordinator
Human Pharmacology and
Clinical Neurosciences Research Group
Director
Neurosciences Research Programme
PRBB Building (office 221.03)
Doctor Aiguader, 88, 1rst floor
08003 Barcelona
Tel. 933 160 484 | Fax +34 933 160 467
rtorre@imim.es
www.imim.es / www.imim.cat
Summary of project summary or current research lines (less than 300 words).
Hydroxytyrosol is one of the most potent antioxidants of dietary origin (mainly olive oil
and to a lower extent wine). Additionally it is a minor dopamine oxidative metabolite. In
several clinical studies it has been possible to demonstrate that this compound is
generated endogenously from tyrosol a simple phenol of dietary origin. The enzyme
regulating this biotransformation is CYP2A6 an isoenzyme of cytochrome P450.
CYP2A6 in humans display a genetic polymorphism leading to enzymes with different
catalytic activities. Beneficial health derived effects from this biotransformation would
be regulated by CYP2A6 genotype.
The master offered includes the set-up of the technique for CYP2A6 genotyping and its
application in human subjects (n=60) that will participate in a cross-over, randomized
clinical trial. Subjects will be administered with several treatments monitoring the
generation of hydroxytyrosol, and the impact on endothelial function and secondary
biomarkers of cardiovascular diseases. The applicant will have the opportunity at
investigating the impact of CYP2A6 genetic polymorphism on tyrosol to hydroxytyrosol
biotransformation and cardioprotective derived effects.
20
Project Title: Pharmacological modulation of voltage-gated calcium CaV2.1 channels
with therapeutic potential in the treatment of hemiplegic migraine and ataxic
syndromes.
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Dr. José M. Fernández Fernández
Tenured Assistant Professor
Laboratory of Molecular Physiology and Channelopathies (Room 341)
Department of Experimental and Health Sciences
University Pompeu Fabra-PRBB; C/ Dr. Aiguader, 88; 08003 Barcelona
Phone: 933160854; e-mail: jmanuel.fernandez@upf.edu; http://www.upf.edu/fisio/
Summary of project summary or current research lines (less than 300 words).
Human mutations in the CACNA1A gene, encoding the pore-forming 1A subunit of the
voltage-gated CaV2.1 calcium channel, cause multiple neurological disorders including
both familial and sporadic hemiplegic migraine (FHM/SHM), Episodic Ataxia type 2
(EA2) and Congenital Ataxia. Hemiplegic Migraine (HM) mutations induce a gain of
CaV2.1 channel activation that specifically enhances cortical excitatory transmission to
favor initiation and propagation of cortical spreading depression, a key process in
migraine pathophysiology. This effect may be further facilitated by the lower direct G
protein-mediated inhibition of CaV2.1 channels reported for several FHM mutations.
Pharmacological evidence suggests that inhibition of channel activity has strong
potential to provide a new therapeutic approach for the treatment of both HM and
common migraine. Besides, some HM gain-of-function mutations also led to cerebellar
atrophy and congenital ataxia.
On the contrary, EA2 mutations produce loss of CaV2.1 channel function that in
some cases are due to an increase in the voltage threshold required to gate the
channel. Correcting this defect by using channel activators may be useful in treating
the disease.
Currently no selective CaV2.1 modulators exist that are suitable for therapeutic
use, encouragingly however recent discoveries highlight some starting-point molecules
with potential to generate new suitable therapeutic tools. We aim: 1) the design and
the identification of novel, selective CaV2.1 channel inhibitors/activators which
reverse the gain/loss of channel function produced by Hemiplegic Migraine
(HM)/EA2 CACNA1A mutations, and 2) to fully explore the potential of this
mechanism to produce a treatment for these medical conditions and migraine in
general. The work will involve the use of electrophysiological techniques on cell lines
expressing wild-type or FHM/EA2 mutant channels, to test de novo designed small
molecule, selective CaV2.1 modulators (in collaboration with researchers from the
University of Sussex, United Kingdom).
Related Publications by the group leaded by Dr. Fernández in the last five years:
1. Vila-Pueyo et al. Eur. J. Paediatr. Neurol. doi:10.1016/j.ejpn.2013.12.011 (2014)
2. Carreño et al. Mol. Genet. Genomic Med. 1(4): 206-222 (2013)
3. Weiss et al. J. Biol. Chem. 287: 2810-2818 (2012)
4. Serra et al. P.N.A.S. 107(4): 1672-1677 (2010)
5. Serra et al. Pflugers Arch. 458(3): 489-502 (2009)
6. Cuenca-León et al. J. Neurol. Sci. 280(1-2): 10-14 (2009)
7. Corominas et al. Neurosci. Lett. 455(2): 105-109 (2009)
21
Project Title: Snail1 function and activated fibroblasts in epithelial tumorigenesis
Project supervisor: Antonio García de Herreros, Programa de Recerca en Càncer,
IMIM-Hospital del Mar, Parc de Recerca Biomèdica de Barcelona, Room 298.03,
agarcia@imim.es, Tel 93 – 3160433.
Orientative project summary or summary of current research lines:
Years ago our group reported that Snail transcriptional factor down-regulated Ecadherin expression and induced an epithelial-mesenchymal transition (EMT) in tumor cells
(Batlle et al 2000, Nature Cell. Biol. 2: 84-89). Our group has kept working on this transcriptional
factor that is the main object of our research, not only as an E-cadherin repressor but also as an
inductor of EMT. Therefore we have studied targets of Snail1 relevant for EMT and other effects
of Snail1 in epithelial cells, such as the induction of invasiveness, resistance to apoptosis or
stemness traits. We have also analyzed in detail the mechanism of epithelial gene repression
by Snail1 in genes directly inhibited by this factor, determining how Snail1 modifies epigenetic
marks (Herranz et al 2008, Mol Cel Biol, 28, 4772; Herranz et al 2012, Mol. Cell, 46, 369;
Villagrasa et al, 2012 Oncogene 31, 4022) and also characterize the mechanism used to
activate mesenchymal genes (Stanisavljevic et al 2011, J. Cell Sci., 124, 4161). We have also
studied how Snail1 transcriptional activity is controlled. Recently we have identified two new
Snail1 ubiquitin ligases modulated by several cellular stresses and explaining the rapid Snail1
stabilization in these conditions. (Viñas-Castells et al, Nucl. Acids Res. 42, 1079, 2014). Another
interesting information provided by our group have consisted in the characterization of a
relevant role for repetitive subcentromeric RNAs in EMT and the demonstration that these
RNAs, such as major satellites in murine cells, are under the transcriptional control of Snail1
(Millanes et al., Mol Cell 2013, 52, 746).
The most recent work of the group has been focused on the relevance of Snail1
expression in the tumoral stroma. We have described that Snail1 expression is detected in few
cases in the epithelial component of the tumors, whereas is often observed in the stroma
(Franci et al. 2006, Oncogene, 25, 5134), more specifically in activated fibroblasts. Snail1 is
necessary for the maintenance of the undifferentiated phenotype of mesenchymal stem cells a
cellular entity very similar to cancer activated fibroblasts. Snail1 depletion causes the premature
differentiation of these cells to adipocytes or osteoblasts (Batlle et al., 2013, Oncogene 32,
3381). Moreover, our results indicate that activation of mesenchymal stem cells or fibroblasts
with TGF- is impaired in Snail1 KO cells; Snail1 is required for a full transcriptional as well as
functional response to this cytokine. We are currently characterizing the effect of Snail1
expression in fibroblasts on the coadjuvant effect of these cells on tumoral cell invasion and
implantation. Our results indicate that in the presence of fibroblasts the invasive capability of
tumoral cells is markedly enhanced, supporting the well-known effect of the stroma on tumor
development. Snail1 expression in fibroblasts is required for this supportive effect. The
molecular basis of these effects is being investigated, both in vitro assays and in tumor animal
models. Our results indicate that active fibroblasts exert two different actions: 1) secrete a
collection of signalling molecules triggering invasion of epithelial cells; and 2) reorganize the
extracellular matrix providing an ordered platform leading to directed migration (Stanisavljevic et
al 2015, Cancer Res. 75, 284). The student will perform his research project on this topic.
For a more complete list of publications of the group on this or other topics or research
interests see http://www.imim.es/programesrecerca/cancer/ubcm.html
22
Project Title: Molecular Mechanisms of endocytic traffic in health and disease.
Project supervisor
María Isabel Geli. Ph. D.
Investigador Científico del CSIC
Department of Cell Biology
Instituto de Biología Molecular de Barcelona
Parc Científic de Barcelona
C/ Baldiri Reixac 15
08028
Phone 00 34 934020197
e-mail mgfbmc@ibmb.csic.es
Summary of project summary or current research lines
We aim at unveiling the molecular mechanisms supporting endocytic traffic in health and
disease, using the yeast S. cerevisiae and mammalian cultured cells as model systems. Our
current projects focus in the retromer, clathrin and actin dependent retrograde transport from
endosomes to the plasma membrane and the Trans Golgi network, pathways directly related to
the development of neurological diseases such as Late Onset Alzheimer Disease (LOAD). We
are currently following two exciting projects dedicated the first to a novel and evolutionary
conserved calcium-calmodulin regulated pathway leading to disassembly of clathrin from
endosomal membranes. In collaboration with the group of P. Gorostiza (IBEC), we are
designing photo-pharmacology tools, a state of the art technology, to dissect this pathway. A
second research project has identified an inhibitor of WASH, the major endosomal actin
nucleating promoting factor, implicated in the generation of retromer transport intermediates.
Preliminary data suggest that this protein is an interesting target for the development of drugs
against LOAD. Depending on his/her skills and research interests, the Master student will
develop a small research project, either focus in dissecting the molecular mechanism of
membrane traffic or defining the biomedical implications of our research.
Selected research articles from the group:
F.-Z. Idrissi et al. (2008) “ Distinct acto/myosin-I structures associate with endocytic
profiles at the plasma membrane” J. Cell Biol. 180: 1219-32.
H. Grötsch et al. “Calmodulin dissociation regulates Myo5 recruitment and function at
endocytic sites” EMBO J. (2010) 29: 2899-914.
F.-Z. Idrissi et al. “Ultrastructural dynamics of proteins involved in endocytic budding” (2012)
Proc Natl Acad Sci U S A. 109: E2587-94.
I-M. Fernández-Golbano, F-Z. Idrissi, J. P. Giblin, B. L. Grosshans, V. Robles, H. Grötsch, M.
M. Borrás and M- I. Geli*. “A cross-talk between PI(4,5)P2 and CK2 modulates actin
polymerization during endocytic uptake” (2014) Dev Cell. 30, 746-758.
23
Project Title:
"Identification of copy number alterations that are targets for available drugs and are
involved in T-ALL leukemogenesis and prognosis "
Project supervisor :
Eulàlia Genescà-PhD
ALL Research Group
Josep Carreras Leukaemia Research Institute (IJC)
Carretera de Canyet s/n, camí de les escoles. Edifici IMPPC
08916, Badalona (Barcelona), SPAIN.
Tel: +(34) 93 557 28 08/ + (34) 93557 28 07
egenesca@carrerasresearch.org
http://www.carrerasresearch.org/ca/acute-lymphoblastic-leukemia-all-_3726
Summary of project summary or current research lines (less than 300 words).
Acute Lymphoblastic Leukemia (ALL) is still a non-curable neoplasia mainly in adult
patients. The survival rates for ALL are much lower in adults than in children. The reasons for
this survival difference lie largely in the higher frequency of poor prognosis subtypes of ALL in
adults and a poorer tolerance of the treatment as age increases. Except for some selected
subgroups, such as Ph+ ALL for example, the current therapeutic protocols for adult ALL do not
take into account the differences in the molecular background of the disease. This is especially
evident in the adult T-ALL subtype, in which the same treatment protocol for B-precursor ALL
is used in spite of its different molecular basis. T-ALL is currently also the subtype with fewer
new therapeutic alternatives available. Therefore, if we want to improve the survival of patients
with ALL we first need to obtain detailed and relevant molecular information to enable doctors
to accurately define the risk and decide on the treatment. Secondly, we need to have specific
therapeutic alternatives available to apply to these new oncogenetic ALL subgroups. To do this
we need to focus translational research to redefine risk classification so it is also based on
oncogenetic information, while at the same time having new target therapies available (more
specific treatments with fewer side effects) for adult ALL patients.
The aims of the project are: firstly to validate some of the genetic markers recently
identified by other cooperative leukemia working groups in the specific Spanish T-ALL cohort
that has been treated homogeneously by following the PETHEMA treatment protocol.
Secondly, we will assess the anti-leukemic effect of the available drugs that specifically target
these genes in an in vivo model. We also want to check if CNAs identified in other blood
neoplasias; such as Acute Myeloblastic Leukaemia (AML), Non-Hodgkin Lymphoma (NHL)
and Chronic Myeloid Leukaemia (CLL), or in solid cancers as Melanoma and Breast Cancer;
could also have an impact on T-ALL leukaemia.
24
Project Title: The development of hearing: the regulation of Atoh1 in the embryo.
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Name: Gina Abelló (Visiting Professor) & Fernando Giraldez (Full Professor)
Group: Developmental Biology
Institution: CEXS-UPF at the PRBB, c/Dr. Aiguader 88, 08003-Barcelona
email: fernando.giraldez@upf.edu / gina.abello@upf.edu
phone: (34) 933160838
web page: http://www.upf.edu/devbiol/
Summary of project summary or current research lines (less than 300 words).
Hearing and balance depend on the function of specialised mechanoreceptors, the
inner ear hair cells. The specification of hair cells during development depend on the
expression of Atonal1 (Atoh1) is a basic Helix-Loop-Helix (bHLH) transcription factor
that behaves as a master gene for hair cell development. Atoh1 is necessary and
sufficient for hair cell development. Atoh1 is able to drive hair cell production also in the
adult inner ear and to convert non-sensory cells into hair cells. Therefore, the
regulation of Atoh1 makes the core of hair cell development and regeneration. The aim
of the project is at better understanding the molecular regulation of Atoh1 transcription
in otic progenitors.
Atoh1 expression is mainly dependent on an enhancer situated 3.5kb downstream
Atoh1 coding region that recapitulates its expression during development. The full
understanding of Atoh1 regulation requires the combination of a genome-wide
approach that provides information on genomic landscapes of epigenetic regulation
together with the analysis of specific regulatory domains.
The aim of this project is to use two different methods to analyze the genomic
landscape of Atoh1 and the sites of interaction of bHLH factors. Specific objectives are:
1) Identification of bHLH factor interactions with Atoh1 regulatory regions. Chromatin
immunoprecipitation followed by genome-wide sequencing (ChIP-Seq) to identify
specific DNA sites in direct physical interaction with several bHLH transcription factors
of interest that include Neurog1 and Hey1.
2) Epigenetic profiling of otic pogenitors by means of ATAC-seq. This technique
identifies regions of open chromatin, nucleosome bound and nucleosome-free
positions and provides a footprint of the positions occupied by transcription factors.
Both procedures require the use of a variety of techniques like ChIP-seq, footprinting,
enhancer analysis, and functional assays on chick embryos. Together, the work will
provide a “hands-on” experience on developmental biology.
References:
http://www.ncbi.nlm.nih.gov/pubmed/23724999
25
Project Title:
Synthesis and evaluation of peptides for the delivery of therapeutic proteins across the
Blood Brain Barrier
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Prof. Ernest Giralt (Organic Chemistry, IB)
ernest.giralt@irbbarcelona.org
Tel: +34 93 40 37125
Institute for Research in Biomedicine (IRB Barcelona)
Parc Científic de Barcelona
C/ Baldiri Reixac 10
08028 Barcelona – Spain
http://www.irbbarcelona.org/es/research/design-synthesis-and-structure-of-peptidesand-proteins
Summary of project summary or current research lines (less than 300 words).
5
The presence of the blood-brain barrier (BBB), physiological barrier present in cerebral
blood vessels, limits the access of pharmacological compounds to the brain. Thus,
pharmacological compounds don´t reach their therapeutic target inside the brain.
Recently, the better knowledge of the transport mechanism through the BBB has
resulted in the discovery of certain molecules, BBB shuttles, including peptides, that
cross the BBB and are able to increase the transport of other compounds.
Our hypothesis comprises conjugation of a peptidic BBB shuttle to a model protein
(Green Fluorescent protein) to study the transport properties in a cell-based model of
the blood-brain barrier (bENd.3 cells).
We have divided the project in 3 parts comprising:
1.
Peptide synthesis. Three different peptides described as able to bypass the BBB
will be prepared. These peptides will also be prepared with a reactive moiety
(maleimide) to allow protein modification. In addition, we foresee the preparation of the
peptides including a protease reactive sequence that would allow the separation of the
peptide and the protein. The student will get familiarized with peptide solid-phase and
analytic techniques such as HPLC or Mass Spectrometry. This part of the project will be
the most important.
2.
GFP-BBB shuttle synthesis. Modification of solvent exposed lysines will be the
strategy of choice. The student will learn how to work with proteins and about its
characterization. Techniques such as gel electrophoresis or HPLC will be used.
3.
Study of endocytosis of prepared constructs. Endothelial mouse brain cortex
cells (bENd.3) will be used for studying the endocytic profile of modified and
unmodified GFP derivatives. In these preliminary experiments, the student will learn
cell culture techniques.
26
Project Title:
Cloning, overexpression, purification and functional studies of a proteolytic enzyme
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
F. Xavier Gomis-Rüth
Research Professor CSIC and Head of the Proteolysis Lab
Molecular Biology Institute of Barcelona, CSIC
Barcelona Science Park
c/Baldiri Reixac, 15-21; Helix Bildg.
08028 Barcelona
e-mail xgrcri@ibmb.csic.es; phone 934 020 186
Direct supervision at the bench will be carried out by an experienced member of the
hosting lab.
Summary of project summary or current research lines (less than 300 words).
For biotechnological applications and assays of enzymes and other proteins it is indispensable to be able to produce sufficient amounts of pure material with which to perform biophysical, biochemical, functional and structural studies. The aim of the present module is to provide students of the BIOMED Master’s Degree with the required practical skills to obtain large amounts (in the milligram range) of purified proteins as part of a wet­lab practicum in a biochemical laboratory dedicated to basic research. For this, the selected student will be introduced into key techniques aimed at cloning, recombinant overexpression, chromatographic purification of proteins, and functional assays under the guidance of an experienced researcher.
27
Project Title: Role of genomic inversions in complex disesases
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Juan R González, Associate Research Professor at CREAL and Adjunct Professor at
UAB
e-mail address: jrgonzalez@creal.cat
url: http://www.creal.cat/brge.htm (includes information about Professional
Biosketch, Google Academy Profile and Software development web page)
Summary of project summary or current research lines (less than 300 words).
Despite a major genetic contribution to the etiology based on epidemiological and
genomic data, there is still a significant proportion of missing heritability in most
complex diseases. In order to study still unexplored genetic variants, we have recently
developed two bioinformatic tools to detect and genotype chromosomal inversions
using SNP array data (inveRsion http://www.biomedcentral.com/1471-2105/13/28/
and invClust
http://nar.oxfordjournals.org/content/early/2015/02/05/nar.gkv073.full.pdf). These
tools allowed us to detected a list of ~60 inversions (including some of the already
known inversions). By using a large population-based cohort, we have also shown that
these inversions affect gene expression and methylation profiles. In addition, we have
also assessed the effect of these inversions in some phenotypes (asthma, cancer and
brain-related diseases). In this project the student will focus on deciphering how
inversions affects both epigenomics and transcriptomics as a marker to predict the risk
of developing common diseases such as asthma, obesity or cancer. To this end,
different multivariate techniques developed in our group will be use to integrate
different omic data already available for these selected diseases.
28
Project Title: PI3K signalling and sprouting angiogenesis
Project supervisor (besides your name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Mariona Graupera, PhD
Vascular Signalling lab
Angiogenesis Unit
Institut d´Investigació Biomèdica de Bellvitge (IDIBELL)
Hospital Duran i Reynals - 3ª Planta
Gran Via de l’Hospitalet 199-203
08908 L´Hospitalet de Llobregat , Barcelona, Spain
Tel: +34932607404
FAX: +34932607426
e-mail: mgraupera@idibell.org
Summary of project summary or current research lines (less than 300 words).
Angiogenesis or new blood vessel formation is essential for normal physiological
events such as embryonic development, wound healing and reproduction and also
plays a critical role in the progression of many pathologies, including cancer. Within an
angiogenic sprout, the endothelial population is not homogenous. The tip of vascular
sprouts consists of a single endothelial cell that extends multiple long filopodia in a
polarized manner (Fig ii.). In contrast, the ECs that follow the tip cells, termed stalk
cells, produce very limited number of filopodia but instead proliferate when stimulated
with VEGF-A. Pericytes instead, are
solitary, smooth muscle-like mural cells
that invest the wall of microvessels. These
cells extend long cytoplasmic processes on
the abluminal surface of the endothelial
cells, making tight contacts that are
important for blood vessels stabilization,
remodelling and function. Our studies are
focused on understanding how the PI3K
signaling pathway in endothelial cells and
pericytes
regulates
the
sprouting
angiogenic process. For that, we rely on
detailed observation of stereotyped
vascular patterning in normal and
genetically modified mouse retina and
hindbrain as well as in vitro studies using
endothelial cells and pericytes isolated
from the mutants. We will ultimately seek
to explore if PI3K selective inhibitors as
anti-angiogenic therapy is of any therapeutic benefit and makes this strategy a strong
contender for use in anti-angiogenic therapy. To address this point we have set up
several tumour models in which we inhibit PI3K genetically and pharmacological.
29
Project Title:
Isolation of molecular determinants of protein oxidation and aggregation.
Project supervisor:
Elena Hidalgo
Universitat Pompeu Fabra
C/ Dr.Aiguader 88
08003 Barcelona
Tel. 34-93-316-0848
Fax. 34-93-316-0901
elena.hidalgo@upf.edu
Summary of current research lines.
Our group is interested in studying the components and molecular mechanisms
which regulate the responses to oxidative stress and the control of the cell
cycle, using the fission yeast Schizosaccharomyces pombe as a model
system. To obtain more information about the laboratory and about our
research interests, please consult our group’s web page (www.upf.edu/osccg).
Some recent publications include:
García-Santamarina et al. 2014. Nature Protocols 9(5):1131.
García et al. 2014. Nucleic Acids Res. 42:10351.
Calvo, I.A. et al. 2013. Cell Reports 5:1413.
Ivanova, T. et al. 2013. Mol. Biol. Cell 24:3350.
Fernández-Vázquez et al. 2013. PLoS Genet. 9:e1003647.
Calvo, I.A. et al. 2012. Nucleic Acids Res. 40:4816.
Gómez-Escoda et al. 2011. EMBO Rep. 12:84.
Zuin, A. et al. 2010. EMBO J. 29:981.
Moldón et al. 2008. Nature 455:997.
Using the Huntington disease-related, aggregation-prone protein Huntingtin as
a reporter of aggregation, we have isolated genes which modulate its
aggregation; our aim is to characterize them.
30
Project Supervisor:
Name: Matthew Ingham / Raul Alcantara
Group: Production Bioinformatics
Institution: Centre Nacional D'Analisi Genomica
email: mingham@pcb.ub.cat
web page: http://www.cnag.cat/
Project Title:
Development of a specialised contamination detection system for bisulfite treated
samples that have undergone DNA sequencing.
Summary:
The CNAG has become a worldwide leader in bisulfite sequencing, which through the
conversion of un-methylated cytosine bases to thymine allows us to study DNAmethylation
and its role in cancer, aging, atherosclerosis, and other genetic phenomenae.
Detecting contamination in such samples is a vital part of quality control within the DNA
sequencing pipeline. In the case of bisulfite treated samples, however, the conversion
of un-methylated cytosine bases to thymine causes serious challenges to the standard
procedure of using BLAST to assign an organism to unaligned sequences as no such
bisulfite BLAST database yet exists.
The goal of the project is to create a BLAST database of “converted” DNA which will
allow us to detect contamination in bisulfite samples, and to create an easy to use
system that will generate a report which summarizes the BLAST results.
The Master's student will be exposed to many important aspects of bioinformatics
including alignment of millions of sequences using different algorithms and parameters,
parsing of results, database design, parallelisation on a computing cluster, sequence
data quality evaluation, and analysis. It will also involve exposure to a wide variety of
projects with applications including whole genome sequencing, exome capture, mRNA,
micro RNA, and bisulfite treatment. Overall, the project will provide the student with
invaluable experience they will be able to use anywhere in the genomics community.
References:
Raineri E, Dabad M, Heath S (2014) A Note on Exact Differences between Beta
Distributions in Genomic (Methylation) Studies. PLoS ONE 9(5): e97349.
doi:10.1371/journal.pone.0097349
Expected skills:
Strong Unix skills and some bash scripting
Perl and/or Python
Experience with sequence alignment preferred but not required
Possibility of funding:
None
31
Project Title:
Chromatin regulation of human and viral gene expression
Project supervisor
Albert Jordan, PhD, Científic Titular CSIC, Group leader
Institut de Biologia Molecular Barcelona IBMB-CSIC
Parc Científic de Barcelona, Baldiri i Reixac, 4, 08028 Barcelona
Tel. + 34 93 402 0487
e-mail: albert.jordan@ibmb.csic.es
url: http://www.ibmb.csic.es/home/ajordan (Dept. Molecular Genomics)
Orientative project summary or summary of current research lines
We focus our research on the control of gene expression in human cells by chromatin
organization, components and modifications. The degree of compaction of chromatin affecting a
gene promoter dictates accessibility to transcription factors and RNA polymerase, and many
chromatin modifying enzyme families act to overcome difficulties imposed by chromatin.
We investigate the role and specificity of histone H1 variants in chromatin organization and gene
expression control. By RNA interference of the different human H1 variants we have found that
they have different involvement in cellular processes such as cell cycle progression, in different
cell types. We have also described a differential role of H1 variants in pluripotency and
differentiation. Currently, we are investigating the occupancy of H1 variants genome-wide by
ChIP-chip and ChIP-seq (NGS).

Millán-Ariño Ll, Islam A, Izquierdo-Bouldstridge A, Mayor R, Terme JM, Luque N, Sancho
M, López-Bigas N, Jordan A (2014) Mapping of six somatic linker histone H1 variants in
human breast cancer cells uncovers specific features of H1.2. Nucleic Acids Research. doi:
10.1093/nar/gku079

Terme JM*, Sesé B*, Millán-Ariño L, Mayor R, Izpisua-Belmonte JC, Barrero MJ, Jordan A
(2011) Histone H1 variants are differentially expressed and incorporated into chromatin
during differentiation and reprogramming to pluripotency. Journal of Biological Chemistry
286(41):35347-57

Sancho M, Diani E, Beato M, Jordan A (2008) Depletion of human histone H1 variants
uncovers specific roles in gene expression and cell growth. PLOS GeneticsOct;4(10):e1000227.
In a second line of research, we use an HIV promoter model to investigate the influence of
chromatin organization at the integration site on HIV expression, with a focus on the role of
heterochromatin and transcriptional interference on the establishment of viral latency.

Gallastegui E, Marshall B, Vidal D, Sanchez-Duffhues G, Collado JA, Alvarez-Fernández C,
Luque N, Terme JM, Gatell JM, Sánchez-Palomino S, Muñoz E, Mestres J, Verdin E,
Jordan A (2012) Combination of biological screening in a cellular model of viral latency
with virtual screening identifies novel compounds that reactivate HIV-1. Journal of Virology
86(7):3795-3808.

Gallastegui E, Millán-Zambrano G, Terme JM, Chávez S and Jordan A (2011) Chromatin
reassembly factors are involved in transcriptional interference promoting HIV latency.
Journal of Virology 85(7):3187-202.

Jordan A, Bisgrove D, Verdin E. (2003) HIV reproducibly establishes a latent infection after
acute infection of T cells in vitro. EMBO Journal 22: 1868-1877.
32
Project Title: Early life ADHD symptoms childhood and long-term association to
adolescent neurobehavioral outcomes
Project supervisor Dr. Jordi Julvez, a Researcher from CREAL (Miguel Servet fellow)
(jjulvez@creal.cat, 93 214 73 31, Centre for Research in Environmental EpidemiologyPRBB, C. Doctor Aiguader 88, 08003 Barcelona, Spain, www.creal.cat )
Summary of project summary or current research lines
INMA-Menorca is a population-based birth cohort study that includes the assessment
of 400 children from pregnancy to adolescence. The overall objective is to discover the
neurodevelopment (cognitive, behavioural) effects of early life exposures from physical,
biological, psychological and societal environments. The project allows us to examine
the maturation of the CNS and endpoints that potentially have long-term impacts (e.g.,
attention deficits, impulsivity, and hyperactivity). A few studies have assessed the longterm associations of different neurodevelopment phenotypes. The objective of the
present work is to understand the association between attention-deficit hyperactivity
disorder (ADHD) symptoms at preschool age and neuropsychological functioning at 14
years old.The student will learn how to manage epidemiological data, from data
depuration to the use of multivariate regression models. Additionally He/She will learn
how to write a manuscript: Starting with literature review, followed by writing and
performing the analyses plan, and finally the student will write an original contribution.
The final intention is to get it submitted into an international journal.
33
Project Supervisor
Name: Steven Laurie
Group: Data Analysis Team
Institution: CNAG
email: slaurie@pcb.ub.es
web page: http://www.cnag.cat/team/bioinformatics/bioinformatics-analysis-group-data-analysis-team/
Project Title
Exploration and characterisation of the ExAC dataset
Summary
One of the major roles of the Data Analysis Team at CNAG is to analyse data generated by Whole Exome Sequencing
(WES) projects, in order to help our collaborators identify variants that may be responsible for rare human diseases. As
such projects initially produce huge numbers of candidate variants, one useful filter is to remove any variants that are
commonly observed in human populations, as these are unlikely to be related to disease.
The team of Daniel Macarthur at the Broad Institute, recently released by far the largest publicly available dataset of
exome variant calls, consisting of data from 61,486 unrelated individuals (http://exac.broadinstitute.org/about),
describing 9.5 million different variants. In addition to being a valuable resource for filtering of WES results, it is also
an interesting dataset to analyse in further detail, since we can learn more about the different classes of mutation that
affect the exome.
The aim of this project is to analyse this dataset in depth, providing detailed information regarding the frequency of
different types of mutation observed in the human exome (e.g. synonymous, non-synonymous, nonsense, splice-site
affecting SNPs, indels etc.) and identify which genes are more, or less, prone to mutation. This is a very raw dataset,
and therefore the candidate will need to utilise standard data-munging skills, performing preliminary data analysis and
cleaning prior to generating an in-depth report. The final objective will be to provide a detailed report, with graphs and
tables generated using R, that clearly summarises the dataset, and any interesting findings.
The student will have the opportunity to see how CNAG works from the inside, participate in team meetings, and
present their results to the team. She/he will gain experience in the critical appraisal of cutting-edge scientific results,
data analysis, and communication of results.
Background Reading
Macarthur DG et al, 2014: Guidelines for investigating causality of sequence variants in human disease.
http://www.ncbi.nlm.nih.gov/pubmed/24759409
Bamshad et al, 2011: Exome sequencing as a tool for Mendelian disease gene discovery.
http://www.ncbi.nlm.nih.gov/pubmed/21946919
Biesecker LG & Green RC, 2014: Diagnostic clinical genome and exome sequencing.
http://www.ncbi.nlm.nih.gov/pubmed/25229935
Expected Skills
The student will work entirely within a Linux/Unix environment, and as such should be comfortable using the
command line, and confident writing simple scripts in the language of their choice e.g. perl, python, bash. The
student
should also have some experience using R to analyse data and produce simple figures, since this will be a key
aspect of
the project. However, the goal is to improve these skills, so there is no need to be an expert.
Possibility of Funding
None
34
Project Title: Role of the MAP kinase ERK5 in prostate cancer proliferation.
Project supervisor
Dr Jose Miguel Lizcano
Professor Agregat
Head of UAB Laboratory of Protein Kinases and Signal Transduction
Dept. Bioquímica & Institut de Neurociències
School of Medicine, Universitat Autònoma de Barcelona
Email: josemiguel.lizcano@uab.cat
Tel. 935 813 076
http://orcid.org/0000-0002-3154-5383
Web: http://inc.uab.cat
Summary of project summary or current research lines (less than 300 words).
Prostate cancer (PCa) is the most commonly diagnosed cancer and the second
commonest cause of cancer related death in men in the western world. For most of the
cases, PCa is initially androgen-dependent so patients are usually treated with androgen
deprivation therapy. However, after remission the tumor frequently progresses into a
state of castration resistance, and available treatment options are only palliative in most
cases. Therefore, a better understanding of the signaling pathways might help to propose
new targets for the therapeutic intervention of this type of tumors
We and others have shown the importance of the MAP kinase ERK5 in the progression
and invasivity of human PCa. High levels of nuclear correlate well with malignity and
poor prognosis, and overexpression of ERK5 in prostatic cells induces cell proliferation,
migration and invasion, as well as prostate carcinogenesis. Furthermore, stable prostate
cell lines that overexpress either ERK5 are more efficient forming tumor xenografts,
compared with parental cell lines, and conversely, silencing of either ERK5 induces
growth arrest in these cells.
We have been shown that ERK5 interacts and collaborates with chaperon Cdc37 to
promote cell proliferation and migration in stable prostate cancer PC3 cells (Erazo et al,
Mol Cell Biol 33:1671-86,2013). We have also observed that ERK5 interacts with the
androgen receptor (AR), a protein that plays a pivotal role in prostate cancer, and that
silencing ERK5 inhibits prostate-specific antigen (PSA) promoter activity in response to
androgen-stimulation
Taken together, our working hypothesis is that ERK5, AR and the oncogenic chaperone
Cdc37 collaborate in the tumourigenesis, progression and invasivity of human PCa. The
present project will further explore the molecular mechanisms involved as well as the
functional significance of this interaction. With this project we expect to provide the
basis for the development of new therapeutical strategies to light this type of cancer
35
Project Title:
Inhibition of SUMO conjugation in tumour cell growth arrest.
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Dr. L.Maria Lois
CSIC Assistant Professor, CRAG (CSIC-IRTA-UAB-UB)
Edifici CRAG-Campus UAB, Bellaterra (Cerdanyola del Vallés)
08193 Barcelona, Spain
Tel. +34 93 5636600 ext.3215
email: maria.lois@cragenomica.es
web: http://www.cragenomica.es/es/grupos-de-invetigacion/role-of-sumo-inplantdevelopment
http://www.academia-net.org/profil/phd-l-maria-lois/1135165
http://cost-proteostasis.eu/
https://peerj.com/LMLois/
Summary of project summary or current research lines (less than 300 words).
In eukaryotes, SUMO (Small Ubiquitin Modifier) conjugation to proteins is an
essential process that regulates many aspects of cell biology. Defects in SUMO
conjugation have been associated to cancer, neurodegenerative diseases and others,
raising a great interest in discovering drugs targeting SUMO conjugation. Recent
studies have shown that Myc-overexpressing cancers are strongly dependent on an
active SUMO conjugation.
The student will be involved in tasks related to the development of molecules
displaying high capacity for inhibiting SUMO conjugation in vitro. The identified
molecules will be further characterized regarding their antiproliferative signature over
distinct cancer cell lines. The generated results will constitute the basis for opening a
new line of research addressing the molecular mechanisms involved in
SUMOylationdependent tumor cell proliferation in vivo.
The project will be performed in close collaboration with Joan Seoane’s group at
VHIO (http://www.vhio.net/research-team/es_joan-seoane.php) and other research
groups participating in the European COST Proteostasis network
(http://costproteostasis.eu/). The project development will require the use of state-of-the-art
technologies available in drug development and biological studies, including
bioinformatics, biochemical, structural and cell biology approaches.
Student candidates are expected to show a remarkable capacity for learning,
commitment and enthusiasm for research. As formative activities, the student will
participate in weekly lab meetings and in intraprogram and institutional meetings. It is
expected that selected candidates will eventually enrol in a PhD program for pursuing
doctoral studies.
A partial travel reimbursement could be arranged.
Interested candidates should contact Dr. Maria Lois at maria.lois@cragenomica.es,
including CV and motivation letter (english, catalan or spanish)
Before the final selection, a personal interview with the mentor and lab members will
be mandatory.
36
Project Title: Identification and characterisation of the mutation causing
spinocerebellar ataxia type 37 (SCA37)
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Antoni Matilla Dueñas BSc MB DSc
Miguel Servet Investigator of the Spanish National Health System
Head of the Functional and Translational Neurogenetics Unit
Genetics Section Editor of The Cerebellum
Health Sciences Institute Germans Trias i Pujol (IGTP)
Ctra. de Can Ruti, Camí de les escoles s/n
08916 Badalona (Barcelona), Spain
Tel.: (+34) 934 978 687
Fax: (+34) 934 978 654
E-mail: amatilla@igtp.cat
Web page: www.btnunit.org
Summary of project summary or current research lines (less than 300 words).
The autosomal dominant spinocerebellar ataxias (SCAs) are a highly heterogeneous group of
rare neurodegenerative diseases characterized by progressive cerebellar ataxia of the gait
variably associated with ophthalmoplegia, pyramidal and extrapyramidal signs, dementia,
pigmentary retinopathy and peripheral neuropathy. Up to date, more than 102 different genes
have been associated to ataxia phenotypes, whereas 46 different loci have been assigned to
SCA phenotypes with 33 defective genes identified. Currently, there are no effective treatments.
Our group and collaborators have identified 2 spanish kindreds originating from Catalonia and
Andalusia where the affected members present with a phenotype characterized by a relatively
pure cerebellar ataxia, dysarthria or clumsiness, and altered vertical eye movement as a distinct
clinical feature. Our genetic linkage studies revealed significant linkage of the SCA37 ataxia
subtype to a 0.66 cM genomic region on 1p32. The Human Genome Nomenclature Committee
assigned this subtype of ataxia the designation of SCA37. Whole exome sequencing (WES)
evidenced that the causative defect lies in a non-coding genomic region or consists of large
repeat expansions or structural variants since it failed to identify any causative coding mutation.
Whole genomic sequence (WGS) in 2 affected patients have delimited the SCA37 critical region
to 1.746 Mb on 1p32. An ataxia causative gene within the delimited region on 1p32 has been
identified.
The project consists of the following specific aims: 1. to identify additional SCA37 pedigrees by
genotyping our cohort of ataxia index cases, negative for other SCAs, with specific SNVs within
the SCA37 critical region; 2. to further analyze and characterize the critical region containing the
SCA37 gene; 3. to study CNVs as candidate causative mutations of SCA37 using CNVs arrays
combined with long-PCR analysis; 4. to study isoform tissue specific expression of SCA37
candidate genes; 5. to experimentally analyze predicted CpG islands identified by bioinformatics
algorithms.
37
Project Title:
Sirtuin-1 and cysteine cathepsins in liver inflammation
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Montserrat Marí, PhD
Department of Cell Death and Proliferation
Institute of Biomedical Research of Barcelona (IIBB-CSIC)
Spanish National Research Council
Centre Esther Koplowitz-IDIBAPS
Rossello 153, 4th floor, Room 4.4
08036-Barcelona
montserrat.mari@iibb.csic.es, monmari@clinic.ub.es
Phone# +34-932275400 ext.4021
Webpage: https://scholar.google.es/citations?user=JfvWZkIAAAAJ&hl=es
http://orcid.org/0000-0002-6116-3247
Summary of project summary or current research lines (less than 300 words).
Sirtuin-1 (SIRT1) at the level of regulating the hepatic metabolism of lipids has been described in recent
years, however there are no studies that show the potential involvement of SIRT1 as a modulator of
hepatic stellate cells (HSC) in fibrosis or inflammation in chronic liver disease, although studies indicate
that the regulation of energy metabolism and inflammation may be connected through a "crosstalk"
between NFKB and SIRT1 antagonistic. In this sense, our preliminary findings indicate that cysteine
cathepsins Cathepsin B and S could mediate the inactivation of SIRT1, and therefore contribute to the
activation of NFKB. Therefore, we aim to analyze:
1) Participation of Cathepsin-SIRT1 axis on the activation and fibrogenic potential of hepatic stellate cells
(HSC).
1a) during activation of primary HSC and LX2 in the human line.
1b) In vivo, in models of experimental fibrosis.
1c) Effect on permeability lysosomal cathepsin SIRT1 axis.
2) Analysis of Cathepsin-SIRT1 axis on NFkB-dependent inflammatory response (in response to LPS or
TNF) in non-parenchymal liver cells using inhibitors of cathepsins SIRT activators and shRNA against
Cathepsin B, or S, or against SIRT1.
2a) In primary HSC and LX2 line.
2b) In Kupffer cells or line THP-1.
2c) in vivo after removal of Kupffer cells by injection of clodronate.
3) Participation of Cathepsin-SIRT1 axis in the hepatic lipid metabolism.
4) Identification of early markers of liver disease in serum of patients with chronic liver disease.
4a) Determination of a pattern "signature" of cathepsins depending on disease etiology.
4b) Generation of a cathepsin microarrays.
38
Project Title:DEVELOPMENT OF THE SPINAL CORD, A MODEL TO STUDY ORGAN
FORMATION, STEM CELL BIOLOGY AND EPYTHELIAL TO MESENCHYMAL TRANSITION
Project supervisor (besides the name, title and position, please include the relevant contact information: email, phone postal address, and webpage).
Elisa Martí
Research Professor
Instituto de Biologia Molecular de Barcelona (IBMB-CSIC)
Parc Cientific de Barcelona
C/Baldiri i Reixac 15-21
Barcelona 08028
elisa.marti@ibmb.csic.es
phone 34-93-4034972
fax 34-93-4034979
http://www.ibmb.csic.es/index.php?pg=laboratorio&tab=lab_home&idLaboratorio=18
Summary of project summary or current research lines (less than 300 words).
The spinal cord contains the nerves that allow us to sense our environment and respond to it
by moving muscles. Knowledge built along the past decade posed the developing spinal cord
as an ideal system to address biomedical questions relevant to organogenesis, stem cell
biology and regenerative medicine. Our group has a long standing interest in the spinal cord,
and is now interested in three particular objectives;
1) To identify the causes of spina bifida by understanding secondary neurulation in animal
models, because environmental and genetic aberrations lead to neural tube closure defects
(NTD) in 1 out of every 1000 births. Our goal is to build a model of neural tube formation and
associated defects (NTDs) combining system analysis of the tissue dynamics, with genetic
manipulation of the zebrafish embryo, and to apply acquired knowledge to understand
secondary neurulation and associated NTDs in amniote embryos.
2) To understand the in vivo control of stem cell determination, because the different modes
of stem-cell division are tightly regulated to balance growth and differentiation during organ
development and homeostasis, and these regulatory processes are subverted in tumor
formation. In the lab we developed markers that provided the single cell resolution necessary
to quantify the three modes of division taking place in the developing nervous system in vivo
(PP/PN/NN). Our goal now is to determine the transcriptome associated to the fate of cell
division and to apply acquired knowledge to understand the mechanisms of neural stem cell
determination.
3) To study the cell shape changes required for early steps in neural development taking the
neural crest cells as a paradigmatic example of an epithelial-to mesenchymal transition. The
neural crest is a multipotent stem cell-like population that originate from the dorsal spinal
cord, and differentiate in a wide range of cell types including the sensory and sympathetic
ganglia of the peripheral nervous system. Because genetic lesions in neural crest progenitors
generate Neuroblastomas, the most abundant solid paediatric tumour, our goal is to
determine the function of newly identified genes in normal and pathological neural crest
development.
39
Project Supervisor:
Name: Marc A. Marti-Renom
Group: Structural Genomics Team.
Institution: CNAG
email: mmarti@pcb.ub.cat
web page: http://www.marciuslab.org
Project Title:
Localization in 3D genomes of genes codding for membrane proteins.
Summary:
Three-dimensional genomics is becoming an important tool for studying how genomes
fold and are regulated. Our group is pioneering the restraint based modeling of
genomes and genomic domains. We develop the TADbit package
(http://3dgenomes.org/tadbit) for modeling and analyzing HiC data. This project will
evolve around determining the structure of as many as possible genomes of bacterial
organisms (at least Caulobacter crescentus) to assess whether membrane protein
genes are near the actual membrane of the organism.
References:
1. Dekker, J., Marti-Renom, M.A. and Mirny, L. "Exploring the three-dimensional
organization of genomes: interpreting chromatin interaction data" Nature
Reviews Genetics (2013) 14 390–403
Get it here: http://tinyurl.com/kxsrt5d
2. Umbarger, M.A., Toro, E., Wright, M.A., Porreca, G.J., Baù, D., Hong, S-H.,
Fero, M.J., Zhu, J., Marti-Renom, M.A., McAdams, J.H., Shapiro, L., Dekker,
J. and Church, G.M. "The three-dimensional architecture of a bacterial genome
and Its alteration by genetic perturbation" Molecular Cell (2011) 44 252–264
Get it here: http://tinyurl.com/n66smod
Expected skills:
Good skills with a Python language. Knowledge of bacterial biology.
Possibility of funding:
None.
40
Project Supervisor:
Name: Marc A. Marti-Renom
Group: Structural Genomics Team.
Institution: CNAG
email: mmarti@pcb.ub.cat
web page: http://www.marciuslab.org
Project Title:
Homology derived restraints for high- resolution structure modeling of protein-ligand
complexes.
Summary:
Advances in structural biology, including structural genomics, have resulted in a rapid
increase in the number of experimentally determined protein structures and
protein/ligand complexes. Part of the current targets for proteins structure
determination has been selected because of potential therapeutic value. There is a
need for tools for automatic and comprehensive prediction/analysis of protein- ligand
interactions. The broad objective of this project is to improve, and validate tools for
comparative docking that will comprehensively describe proteins structures and their
interacting molecules. The application of such methods will result in a list of pairs of
proteins and their interacting partners within the Tropical Disease Initiative
(http://tropicaldisease.org).
References:
Marti-Renom, M. A., Rossi, A., Al-Shahrour, F., Davis, F. P., Pieper, U., Dopazo, J., &
Sali, A. (2007). The AnnoLite and AnnoLyze programs for comparative annotation of
protein structures. BMC Bioinformatics, 8 Suppl 4, S4.
doi:10.1186/1471-2105-8-S4-S4
Martínez-Jiménez, F., Papadatos, G., Yang, L., Wallace, I. M., Kumar, V., Pieper, U., et
al. (2013). Target Prediction for an Open Access Set of Compounds Active against
Mycobacterium tuberculosis. PLoS Computational Biology, 9(10), e1003253.
doi:10.1371/journal.pcbi.1003253
Expected skills:
Good skills with a scripting language. Good knowledge of structural biology.
Possibility of funding:
None.
41
Project Title: Severe malaria and miRNAs: a path towards new diagnostic and
prevention tools for severe infectious pathologies
Project supervisor:
Alfredo Mayor, PhD
Principal Investigator-Associate Research Professor
Instituto de Salud Global de Barcelona (ISGlobal) - Barcelona Centre for International
Health Research (CRESIB)
Universitat de Barcelona-Hospital Clinic
08036 Barcelona (Spain)
Tel.: (+34) 227 54 00, ext 4519; Mobile: (+34) 686 444 183
E-mail: agmayor@clinic.ub.es
Webpage:
http://www.isglobal.org/researcher?p_p_id=viewpersona_WAR_intranetportlet&p_p_lifecycle=0&p_p_col_id=column3&p_p_col_count=1&_viewpersona_WAR_intranetportlet_struts_action=%2Fview%2FpersonaView&_viewpersona_WA
R_intranetportlet_personaId=3300&_viewpersona_WAR_intranetportlet_typeOfPeople=researcher
Summary of current research line:
In pediatrics, and especially in developing countries where diagnostic methods are
scarce, some severe infectious diseases such as pneumonia (bacterial or viral) and
severe malaria (SM) are difficult to distinguish clinically because of the inespecifity of
their symptoms. The discovery of biomarkers specific for these severe pathologies is
important for the development of new methods for the early identification of critically ill
patients and their adequate therapeutic management. This is therefore a research area
with a high potential for translation to clinical practice in the fight against diseases of
global impact. Sequestration of Plasmodium falciparum in host organs through
cytoadhesion of infected erythrocytes (IEs) to host receptors is a central pathogenic
event mediated by parasite proteins expressed on the surface of the IEs (P. falciparum
erythrocyte membrane protein 1 [PfEMP1]). The hypothesis of this project is that host
tissues damaged by the sequestration of P. falciparum secrete microRNAs (a class of
small endogenous RNAs that can regulate genes post-transcriptionally) different to the
ones secreted during uncomplicated malaria or pneumonia. The aim is therefore to
identify microRNAs suitable to predict pathologies associated with SM or pneumonia
that can be developed into diagnostic/ prognostic biomarkers. This research will allow
the development of new methods for early diagnosis of diseases such as malaria and
pneumonia, as well as innovative tools to prevent the sequestration of the malaria
parasite and its adverse consequences. The specific activities to be developed during
the master project include the application of next generation sequencing to identify
miRNAs in human plasmas from malaria exposed and non-exposed population, or the
in vitro cytoadhesion of P. falciparum to identify induction of microRNA expression by
human cell lines.
42
Project Title:
Systemic analysis of virus infection fate regulation
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Andreas Meyerhans, PhD
ICREA Research Professor at the University Pompeu Fabra
Infection Biology Group
Department of Experimental and Health Sciences
Universitat Pompeu Fabra
Doctor Aiguader, 88
Edificio PRBB-3er piso
08003 Barcelona
Spain
Tel. +34-933-160-831
e-mail: andreas.meyerhans@upf.edu
Website: http://www.upf.edu/virologyunit/
Summary of project summary or current research lines (less than 300 words).
Viral infections can be fundamentally categorized as acute or persistent according to their
temporal relationships with their hosts. Acute infections are usually resolved within a few weeks.
By contrast, persistent infections are not resolved and, instead, develop when the immune
response is not sufficient to eliminate the invading virus during the primary infection phase.
Viruses from both categories continue to threaten human health. Notable examples are
Influenza virus and infections with the Human Immunodeficiency Virus or the Hepatitis B and C
viruses.
A number of viral and host factors are involved in the fate decision between an acute and a
persistent infection outcome. However, the key host sensing system is not known and the
relationship between these factors is still poorly understood. A major remaining question is how
the host organism senses the balance between all implied components, and how and when it
decides whether it is worth continuing the fight against the infecting virus or whether it is better
to surrender via downregulating immune effector mechanisms in order to avoid
immunopathology.
Aim of the project is to better understand how the outcome of a non-acutely-lethal virus
infection is controlled. The underlying hypothesis is: a host organism senses the threat of an
infection by means of dynamic virus-host interactions and then decides (i) to keep augmenting
antiviral responses until the virus is eliminated, or (ii) to surrender and down-regulate antiviral
responses to avoid host damage due to continued inflammatory responses.
To address this fundamental and complex issue we use a virus-infection mouse model system
that allows the establishment of acute or persistent infections by inoculating the animals with
different virus doses. Bioinformatics systems analysis of spleen-specific transcriptomes of mice
with different infection outcomes has allowed generating hypotheses on infection fate
regulation. The master thesis will be focused on one of these hypotheses.
43
Project Title: Drosophila as a model in cancer biology
Project supervisor
Marco Milán, ICREA Research Professor,
IRB Barcelona
C/ Baldiri Reixac 10 08028 Barcelona
http://www.irbbarcelona.org/en/research/development-and-growth-control-laboratory
marco.milan@irbbarcelona.org
+34 93 40 34902
Summary of project summary or current research lines (less than 300 words).
Cancer is a multi-hit process involving mutations in oncogenes and tumor suppressors,
as well as interactions between the tumor cells and the surrounding stroma. Cancer as
a disease is characterized by a series of hallmarks, which include sustained
proliferative signalling, resistance to growth suppressors and to cell death, increased
replicative immortality, invasiveness and metastasis, energy metabolism
reprogramming, genome instability, and inflammation. We are interested in the cellular
and molecular mechanisms underlying the regulation of many of these hallmarks,
especially the role of Genome Instability in tumourigenesis.
The fruit fly, Drosophila, is an excellent, genetically-tractable system for modelling the
development of cancer, due to the conservation of signaling pathways, cell proliferation
and survival genes between fly and humans, its suitability for genetic and molecular
manipulations, and its well-described developmental biology. Working with flies (an in
vivo approach) allows the analysis of tumours at the cell autonomous level but also at
the systemic level (relationship between tumours and the rest of the body). Drosophila
is also useful to perform high-throughput screening of small molecule inhibitors that can
be developed to combat human cancer.
44
Project Title: Lipid therapy in hepatocellular damage and cancer:
molecular and experimental models
Project supervisor
Albert Morales, PhD
Department of Cell Death and Proliferation
Institute of Biomedical Research of Barcelona (IIBB-CSIC)
Spanish National Research Council
Centre Esther Koplowitz-IDIBAPS
Rossello 153, 4th floor, Room 4.3
08036-Barcelona
amorales@clinic.ub.es,
albert.morales@iibb.csic.es
Phone# +34-932275400 ext.4545
Webpage: https://scholar.google.com/citations?user=aziENiMAAAAJ&hl=es
Summary of project summary or current research lines (less than 300 words).
The involvement of sphingolipids and cholesterol in lipid rafts, where they control the
intracellular signaling of many receptors, and in pathological processes associated with
cell death and proliferation justifies the use of therapies aimed to:
i) change their composition in diseases where cholesterol and sphingolipids are
affected
ii) in conjunction with drugs in whose actions are involved.
Our results reveal their participation both in hepatocellular injury, during fibrosis or liver
function post-transplantation,and in hepatocarcinogenesis and tumor therapy.
Therefore, and based on our experience in the modulation of these metabolic
pathways, we aim to validate the intervention on bioactive lipids as proof of concept for
the preclinical development of different therapies:
1) Improvement of liver function after modulation of metabolism of
cholesterol/sphingolipids in steatotic organ preserved for transplantation. Since in
murine models of cold ischemia, after genetic or dietary induction of fatty liver,
cholesterol increases liver damage, strategies for preservation improvement will be
analyzed by altering lipid metabolism.
2) Phenotypic reversal of hepatic stellate cells (HSC) through alteration of
sphingolipidic
metabolism:
therapeutic
implications
in
fibrogenesis
and
hepatocarcinogenesis. We have observed that HSC, activated under the control of
sphingolipid-dependent proteins, promote fibrosis and tumor growth. Therefore, in
murine models (wild type and knockouts) pharmacological inhibitors and lipid
modulators will be tested.
3) Lipid therapy to enhance chemotherapeutic efficacy in tumor treatment. It will be
assayed in tumors where alteration of the sphingolipidic metabolism induced by drugs
have been observed (sorafenib in hepatocellular carcinoma and cisplatin in germ cell
tumor), using subcutaneous and orthotopic murine tumor models.
45
Project Title: Handling missing data on radiation epidemiology: A simulation study
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
David Moriña Soler, Postdoctoral researcher, Centre for Research in Environmental
Epidemiology (CREAL)
Email: dmorina@creal.cat
Phone: +34 932 147 317
Postal address: Barcelona Biomedical Research Park (PRBB), C/Dr Aiguader, 88,
08003 Barcelona
Summary of project summary or current research lines (less than 300 words).
Missing data are a very common issue in epidemiological research but their potential to
undermine the validity of research results has often been overlooked in the literature.
Traditional approaches to missing data handling are to include in the analysis only
complete cases —those individuals who have no missing data in any of the variables
required for that analysis—, the default option in many statistical software, or single
imputation —replacing the missing value with, for instance, the mean of that variable.
However, results of such complete cases analyses can be biased. Furthermore, the
cumulative effect of missing data in several variables often leads to exclusion of a
substantial proportion of the original sample, which in turn causes a substantial loss of
precision and power. The single imputation approach based on the mean imputation
has the benefit of not changing the sample mean, but may become problematic for
multivariate analysis as attenuates the correlations involving imputed variables.
In radiation epidemiology, missing data is an especially usual issue and has been
traditionally addressed by complete cases approach or by single imputation.
The first goal of this work will be to study the potential impact of missing data on the
outcomes of interest by means of a simulation study. Cohorts will be simulated on the
basis of realistic assumptions and several missing data scenarios will be considered.
The second goal of the proposed work will be to compare the classical approaches to
handle missing data in radiation epidemiology, like complete cases analysis or single
imputation to more recent alternatives, which usage has increased notably in the last
years, like multiple imputation.
Multiple imputation is a general approach to the problem of missing data that is
available in several commonly used statistical packages. It is able to take into account
the uncertainty due to missing data by creating several different plausible imputed data
sets and appropriately combining results obtained from each of them.
46
Project Title:
Control of proliferation/differentiation in nervous system development.
Project supervisor:
Sebastián Pons,
Científico Titular del CSIC, Instituto de Biologia Molecular de Barcelona.
Baldiri Reixac Nº10, Parc Cientific de Barcelona.
spfbmc@ibmb.csic.es
93-4031103
www.ibmb.csic.es
Current research lines.
The focus of our laboratory has been the neuronal proliferation and
differentiation process. We have used the precursors of the external germinal
layer of the cerebellum (EGL) as a model because is a uniform population of
cells that in postnatal periods suffers spectacular growth. The proliferation of the
precursors of cerebellar granule cells (CGNPs) is governed by the factor Sonic
Hedgehog (Shh) produced by Purkinje neurons. Most notable is that the
precursors stop proliferating when they are closer to the source of production of
Shh. Although PKA activity is almost exclusively regulated by Adenylate
Cyclase, its role in on Shh pathway and on proliferation is very poorly studied,
thus we intend to study the involvement of Adenylate Cyclase on Shh pathway,
using two situations where Shh activity is critical, the cerebellar granule cells of
mouse and the developing chick neural tube. This will allow us to distinguish
between chive and anecdotic events.
Failures of proliferation/differentiation during development often result in
aberrant growths that can be a source of brain tumors at early ages. Our
laboratory has been particularly interested in the medulloblastoma, a tumor of
the posterior fossa that has its highest incidence in children. Anomalies in
different signaling pathways have been implicated in the development of this
pathology. Malfunction of WNT/b-catenin pathway is the cause of a particular
type of medulloblastoma. In a recent work we have demonstrated that
oncogenic forms of b-catenin, contrary to what other oncogenes do, produce
lesions with a low rate of proliferation, but in which the cells remain as
progenitors and do not differentiate, also we have seen that this anomaly is
mainly caused by disturbances in cell polarity caused by b-catenin. We are now
studying how b-catenin controls cell polarity, using the neural tube of chicken
and polarized MDCK cells as models.
47
Gene Regulation in Cell Differentiation and Cancer
A. Postigo
ICREA Professor
Group of Gene Regulation in Cell Differentiation
and Cancer
Institute of Biomedical Research IDIBAPS
idibaps.postigo@gmail.com
IDIBAPS. Cellex, Planta 1B.
Casanova 143. 08036 Barcelona, Spain
http://icrea.cat/Web/ScientificStaff/AntonioPostigo-379
Summary of project summary or current research lines
ZEB proteins (ZEB1 and ZEB2) regulate key master genes during development, cell
differentiation, tumor invasiveness and metastasis (reviewed in EMBO Rep 11:670; Cell Mol
Life Sci, 69:3429). ZEB1 is also involved in regulation of normal cell differentiation in
skeletal muscle (Mol Cell Biol 33:1368). Over the last few years ZEB1 and ZEB2 have
gained great relevance in cancer biology as inducers of an epithelial-mesenchymal
transition (EMT), thus promoting tumor invasiveness and metastasis (Genes & Dev 22:894;
Nat Cell Biol 11:1487; Oncogene 29:3490; PNAS 108:19204; Clin Cancer Res 19:1071; Cell
Death Differ 21:247). Recent work by our group and others indicate that ZEB proteins also
regulate earlier stages of cancer development. On the one hand, ZEB1 and ZEB2 determine
phenotypic and functional stemness in normal and cancer stem cells as well as the
resistance of cancer cells to chemoterapy drugs (Nat Cell Biol 11:1487; Cell Stem Cell 4:336;
Nature Neurosci 12:1369; Cell Stem Cell 6:59; Cell 154:61). On the other hand, ZEB proteins
act as both tumor suppressors as well as mediating oncogenic transformation and
benign-malignant transition induced by signalling pathways such as Wnt, Ras, Notch and
p16/Rb (Cell 47:382, PNAS 108:19204, Mol Cell 38:114, Cancer Cell 15:489; Nature
Comunications 4:2650; Nature Commun 5:5660).
See http://icrea.cat/Web/ScientificStaff/Antonio-Postigo-379 for selected publications by the
group
The selected candidate(s) would have the opportunity not only to develop his/her own
research Master Project but also to get involved in other research lines currently ongoing at
the lab, participate in publications and learn a wide range of molecular and cellular biology
techniques using in vitro and animal models with the eventual goal of entering a PhD program.
Requisites: Bachelor in Biology or another biomedical-related discipline. Candidates with a
strong academic record (higher than 2.8/4.0), previous lab experience and interested in
pursuing later a PhD will receive special consideration in the selection process.
Information. To obtain more information and to set up a visit to the laboratory, please send
CV and the names and contact details of 2-3 persons familiar with the candidate’s academic
or research performance to idibaps.postigo@gmail.com indicating “Master UPF ” in the
subject.
48
Project Title:
Influences of antipsychotic drugs on neural network dynamics in the mouse brain
Project supervisor
Mª Victoria Puig Velasco, PhD (IMIM)
Principal investigator at IMIM (PRBB) in the Neurosciences Programme, group of
“Recerca clínica en farmacologia humana i neurociències“.
Hospital del Mar Medical Research Institute (IMIM)
Carrer del Dr. Aiguader 88, 2nd floor, Office 225
E-08003 Barcelona (Spain)
Tel: 933160482
Email: mpuig3@imim.es
Summary of the project or current research lines (less than 300 words).
The Puig team at IMIM is looking for highly motivated and talented students willing to
participate in a project related to the study of schizophrenia. More specifically, the
project aims at better understanding the cellular mechanisms underlying the actions of
typical vs. atypical antipsychotic drugs. We are currently investigating the influences of
antipsychotic drugs in neural network dynamics via chronic recordings of neural
oscillatory activity in mice trained to perform several cognitive tasks. Data analyses
focus on changes in the communication between different brain regions (alterations in
synchrony of neural activity) due to antipsychotic action. This project combines several
sophisticated techniques such as neuropharmacology, cognitive neuroscience, in vivo
electrophysiology, and computational neuroscience.
We are a young laboratory that has recently launched at IMIM. The student will
participate in this high impact project by helping in chronic recordings of neural network
activity in mice and analysing neural data. The student should have enough knowledge
of neuroscience to understand the goal of the project and the technical approaches
used and be highly motivated to learn new tools in a scientific environment.
References:
Celada P, Puig MV, Artigas F. (2013) Serotonin modulation of cortical neurons and networks.
Frontiers in Integrative Neuroscience; 7:25.
Puig MV, Miller EK (2012). The role of prefrontal dopamine D1 receptors in the neural
mechanisms of associative learning. Neuron; 74(5): 874-886.
Puig MV, Gulledge AT (2011). Serotonin and prefrontal cortex function: neurons, networks, and
circuits. Molecular Neurobiology; 44(3): 449-464.
49
Project Title:
Towards the understanding of cell lineages within the hindbrain during embryonic development Project supervisor
Cristina Pujades, PhD Developmental Biology Laboratory DCEXS‐Universitat Pompeu Fabra PRBB, C/ Dr Aiguader 88, 08003 Barcelona Tel. +34 93 3160839 http://www.upf.edu/devbiol/projectes/cns.html Summary of project summary or current research lines (less than 300 words).
The rhombomere boundary cell population arises at the interface between rhombomeres within the hindbrain. These cells display a specific morphology and gene profiling and they do not undergo neurogenesis, prompting the idea that this population could be a reservoir of neuronal/glial‐precursors. Interestingly, Eph receptors and their Ephrin ligands are expressed in adjacent rhombomeres, and receptor‐ligand interaction takes place only at the interface of their respective expression domains ‐ the rhombomeric boundaries. This leads to bidirectional signalling in boundary neighbouring cells, which prevents intermingling of cell populations with different rhombomeric identity. Interestingly, Eph/Ephrin signalling has been shown important in the maintenance of different stem cell niches in other systems as the intestine so maybe their role in boundaries is also necessary for maintaining this cell population in a stem cell state. We hypothesize the boundary cell population can be a new reservoir of stemcellness within the brain, thus our main aim is to study the fate and behavior of this cell population. For this, we will address: i) how at the interface of two rhombomeres with different cell cohesiveness, the specific boundary cell population is generated and maintained; ii) what is the lineage of hindbrain boundary cells, by cell‐tracing experiments and specific enhancer‐analysis; and iii) how cell fate decisions can affect cell behavior, exploring what boundary cell fate means in terms of neurogenesis and cell cycle behavior by the use of imaging techniques and functional studies. Our model system is the zebrafish embryo because it permits to combine genetic tools with high resolution imaging approaches. The candidate will be involved in the generation of different transgenic lines by the genome editing system CRISP/Cas9, and in the cell lineage analysis of rhombomeric boundary cell population. 50
Project Supervisor:
Name: Emanuele Raineri
Group: Statistical Genomics
Institution: CNAG
email: emanuele.raineri@gmail.com
web page:
Project Title:
Correlation and clustering of noisy genomic data.
Summary:
At the CNAG we generate "tracks" of data in which numerical values are
attached to genomic coordinates. Such tracks might represent for
example frequency of protein binding, methylation status of cytosines,
rate of transcription of a certain DNA stretch, geometrical properties, etc...
I am looking for a student which would help me to write a software to
compute correlations at different scales both between different tracks
and for a single tracks across different genomic loci in a
statistically sound manner.
References:
Expected skills:
Experience in implementing numerical algorithms in C/C++ is mandatory. Some
knowledge of biology a plus.
Possibility of funding:
None.
51
Project Title: DISCOVERING THE FUNCTION OF NEW BLADDER CANCER GENES
IDENTIFIED THROUGH MASSIVE PARALLEL SEQUENCING
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Francisco X. Real
Professor of Cell Biology
Universitat Pompeu Fabra, Barcelona
and
Senior Group Leader
Epithelial Carcinogenesis Group
Centro Nacional de Investigaciones Oncológicas, Madrid
Melchor Fernández Almagro, 3
28029-Madrid (Spain)
Phone +34 917328000 ext 3660
E-mail preal@cnio.es
www.cnio.es
Project to be conducted at the CNIO, Madrid
Summary of project summary or current research lines (less than 300 words).
Massive parallel sequencing (MPS) provides unprecedented opportunities to identify
new cancer genes. We have applied MPS to urothelial bladder cancer gene
identification and are now assessing the role of candidate genes at various levels:
1) the genetics: how prevalent are the mutations? where in the gene/protein do they
occur? are they restricted to specific tumor subtypes? are they specific to discrete
tumor progression pathways?
2) the biology: how do these genes contribute to cancer development/progression? we
use a variety of strategies including knockdown/overexpression and phenotypic
analysis in vitro and in vivo;
3) the clinical application: can the gene mutations identify patients with distinct
outcome? can they be applied to the detection of the tumor in urine?
4) the therapy: can these genes be targeted therapeutically? are there drugs available?
can in vitro or in vivo models be used to assess the therapies?
These are some of the questions the group tackles. If you want to contribute to
answering them, you can work together with students and postdocs in the group to
move the story forward!
Recent publications related to this project
Balbás-Martínez C, et al. Recurrent inactivation of STAG2 in bladder cancer is not
associated with aneuploidy. Nat Genet 2013; 45:1464-1469.
52
Project Title: New therapeutic targets for Leukemia Stem Cells
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Ruth M. Risueño, PhD
Group Leader
Josep Carreras Leukaemia Research Institute
Centre Esther Koplowitz
Rosselló, 149-153
08036 Barcelona
Email: risueno@carrerasresearch.org
Phone: 9. 227 5400 ext.4528
Webpage: http://www.carrerasresearch.org/en/leukemia-stem-cell-group_5586
Summary of project summary or current research lines (less than 300 words).
Acute myeloid leukemia (AML) is a neoplasia characterized by the rapid expansion of immature
myeloid blasts in the bone marrow. The course of the disease is marked by poor prognosis, frequent
relapse, and high disease-related mortality. As such, new therapeutic approaches are required for
remission induction and prevention of relapse. The difficulty in treating AML is thought to arise from a
chemoresistant subpopulation of leukemia stem cells (LSCs) that are capable of maintaining and
reinitiating disease. Our research program focuses on the development of therapeutic strategies for
targeting LSCs.
Due to the higher chemotherapy sensitivity and limited life span of more differentiated AML
blasts, differentiation-based combinatorial therapies that eliminate blasts are a promising therapeutic
approach. As LSCs display the highest differentiation capacity due to the tightly regulated balance
between self-renewal and differentiation, a therapy that favours differentiation would potentially also
exhaust this population and eradicate the cells responsible for the initiation and maintenance of AML. An
in silico screening was performed to search for already FDA-approved drugs that may induce LSC
differentiation and spare healthy hematopoietic stem cells (HSCs). The drugs identified are been validated
in vitro and ex vivo. The mechanism of action of these drugs on AML-LSCs will be characterized and their
potential clinical use for leukemia will be studied. Additionally, new therapeutic targets from the signalling
pathway identified will be evaluated. While describing the signalling pathway implicated in the block of
differentiation will increase the knowledge of the biology that drives the leukemogenesis process,
searching for new drugs that disrupt this intracellular signalling will allow new biomarkers and therapeutic
targets to be defined for AML, and especially LSCs.
53
Project Title: Environmental exposures and molecular omics profiles in children from
six European birth cohorts - the HELIX Project
Project supervisors (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Oliver Robinson, PhD, Postdoctoral researcher, orobinson@creal.cat, 932147362.
Centre for Research in Environmental Epidemiology (CREAL). Doctor Aiguader, 88
08003, Barcelona, www.creal.cat
Maribel Casas, PhD, Postdoctoral researcher, mcasas@creal.cat, 932147364. Centre
for Research in Environmental Epidemiology (CREAL). Doctor Aiguader, 88 08003,
Barcelona, www.creal.cat
Martine Vrijheid, PhD, Professor, mvrijheid@creal.cat, 932147346. Centre for
Research in Environmental Epidemiology (CREAL). Doctor Aiguader, 88 08003,
Barcelona, www.creal.cat
Summary of project summary or current research lines (less than 300 words).
Developmental periods in early life may be particularly vulnerable to impacts of
environmental exposures. Human research on this topic has generally focused on
single exposure–health effect relationships. The “exposome” concept takes a holistic
approach by encompassing the totality of environmental exposures from conception
onward, complementing the genome. The exposome includes an external domain,
measured by methods including geo-spatial modeling, questionnaire and biomonitoring
of external exposures, while the internal domain is commonly assessed through
molecular omics platforms. The internal domain, in part, reflects the biological response
to the external domain. High-throughput molecular biology “omics” techniques (such as
metabolomics, proteomics, transcriptomics, epigenomics) have important potential for
broad and untargeted characterisation of the internal exposome.
The Human Early-Life Exposome (HELIX) project is a new collaborative research
project that aims to implement novel exposure assessment and biomarker methods to
characterize early-life exposure to multiple environmental factors and associate these
with omics biomarkers and child health outcomes, thus characterizing the “early-life
exposome”. In six existing birth cohort studies in Europe, HELIX will estimate prenatal
and postnatal exposure to a broad range of chemical and physical exposures including,
for example, air and water pollutants, persistent organic pollutants and chemical
contaminants of food. The student will analyse the relationship between specific
classes of these environmental exposures and molecular omics profiles (metabolome,
proteome, transcriptome or epigenome) in up to 1,200 children.
54
Project Title:
Involvement of CB1R-5-HT2AR heteromers in cognitive and behavioral alterations in
schizophrenia and their interaction with cannabis use: A translational approach
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Patricia Robledo, PhD
Associate Professor UPF
Principal Investigator in the Human Pharmacology and Clinical Neurosciences Research Group
Neurosciences Research Programme, IMIM-Hospital del Mar Research Institute.
PRBB
Calle Dr. Aiguader 88
Barcelona 08003
SPAIN
probledo@imim.es
Tel: +34 93 316 0455
Summary of project summary or current research lines (less than 300 words).
Despite multiple clinical and pre-clinical studies investigating schizophrenia, the neurobiological
basis of this disease is still unknown. The dysregulation of the serotonergic system, in particular
the 5-HT2A receptor and the endocannabinoid system have been postulated as possible
causes of schizophrenia. A key aspect in the development of schizophrenia is the interaction
between genetic predisposition and age at which cannabis consumption is started. In this
project we propose to investigate, from a translational approach, if the heteromeric formation of
CB1-5HT2A receptor complex might be involved in the emergence of pro-psychotic symptoms
and cannabis use, observed in a large proportion of schizophrenic patients. The elucidation of
this question will be important in the development of a new drug target for the design of more
effective therapies for this disease. In pre-clinical studies we will study the involvement of CB15HT2A heteromers in the pro-psychotic responses induced by 5-HT2A and CB1 receptor
agonists including alterations in sensory gating, reduced sociability and cognitive impairment
using transgenic mice. We will also evaluate the ability of transmembrane interference peptides
that disturb this heteromeric complex to modulate such responses. In parallel, we will quantify
the expression of CB1-5-HT2A receptor heteromers in primary cultures of pro-neurons from the
olfactory neuro-epithelium of patients suffering from schizophrenia consuming or not cannabis,
using PLA immunoassays and confocal microscopy. This highly innovative methodology will
allow the non-invasive, low-cost study of new biomarkers for schizophrenia in a model closely
related to the central nervous system.
55
Project Title:
System-wide phosphoproteome quantitation of different cancer cell lines
Project supervisor (besides the name, title and position, please include the relevant contact
information: e-mail, phone postal address, and webpage).
Eduard Sabidó
Head of the Proteomics Unit
Center of Genomics Regulation
Dr. Aiguader 88
08003 Barcelona
Email: eduard.sabido@crg.cat
Phone: 0034933160834
Summary of project summary or current research lines (less than 300 words).
Protein phosphorylation is a major post-translational modification that constitutes an essential
part of signalling cascades, and modulates the activity and localization of proteins. In this project
phosphorylation events occurring in cellular signalling cascades will be quantified, and the
observed cellular response will be compared between two different cancer cell lines. Despite the
identification of thousands of phosphorylation events, the capacity of systematically
characterizing different phenotypes based on their phosphorylation state is not solved. This
project will address the quantification of relevant phospho-sites in multiple biological conditions
with high sensitivity, specificity and throughput in order to understand the different phenotype of
the selected cancer cell lines. Overall, this work will improve the current functional assignment
of phosphorylation sites by accounting for contextual relationships, and it will represent a step
forward to overcome the current challenges that limit its extended use in large systems biology
studies and personalised medicine.
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Project Title:
Role of new IRP-target mRNAs in Cancer and Iron Biology
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Dr. Mayka Sanchez
Principal Investigator.
Iron Metabolism: Regulation and Diseases Group
Head of Diagnostics in Iron Metabolism Disease (D·IRON)
Josep Carreras Leukaemia Research Institute (IJC)
Crta Can Ruti, Camí de les Escoles s/n
08916 Badalona, Barcelona. Spain
Tel. (+34) 93 554 3077
Fax: (+34) 93465 1472
msanchez@imppc.org
diron@imppc.org
http://tinyurl.com/Sanchez-lab-IMPPC
http://www.imppc.org/resources-and-services/genetic-diagnostics-metabolism-disorders/index.html
http://www.imppc.org/gif/web/
www.carrerasresearch.org
Summary of project summary or current research lines (less than 300 words).
Iron metabolism has been occasionally implicated in cancer; however, the precise
cellular and intercellular mechanisms between both systems are still poorly understood
and so are the pathophysiologic implications. Therefore, understanding the functional
interconnections between iron homeostasis, iron-regulatory proteins and cancer
represents a relevant unsolved scientific challenge with potentially important
implications for clinical practice.
Cellular iron homeostasis is controlled by the iron-regulatory proteins/iron-responsive
element (IRP/IRE) system, where IRPs post-transcriptionally regulate the expression of
mRNAs containing a cis-regulatory element called IRE. My recent discoveries have
revealed that the IRP/IRE network is more extensive than previously thought, and it
controls unexpected mRNAs, most with no obvious association with iron metabolism
and including some with known functional connections to cancer related processes.
These fresh breakthroughs open novel questions about the role of these mRNAs in a
new emerging topic: the pathophysiological implications of iron metabolism in cancer.
The main objective of this project is to elucidate the molecular and cellular connections
between iron homeostasis, the IRPs and cancer; merging biology, bioinformatics and
physiology. We will extensively characterize novel IRP-target mRNAs in silico, in vitro
and in vivo using new methods and bioinformatic tools, unique knock-out mouse
models and human cancer samples. These new mRNAs will be assessed to evaluate
their possible implication as modifier genes for hepatocarcinoma development in
Hereditary Hemochromatosis patients.
Overall, these studies will provide significant insight into the precise molecular
pathways connecting iron and cancer and will contribute in the development of new
strategies for cancer therapies.
57
Project Title:
MUTATIONAL STUDIES IN RARE IRON DISEASES
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Dr. Mayka Sanchez
Principal Investigator.
Iron Metabolism: Regulation and Diseases Group
Head of Diagnostics in Iron Metabolism Disease (D·IRON)
Josep Carreras Leukaemia Research Institute (IJC)
Crta Can Ruti, Camí de les Escoles s/n
08916 Badalona, Barcelona. Spain
Tel. (+34) 93 554 3077
Fax: (+34) 93465 1472
msanchez@imppc.org
diron@imppc.org
http://tinyurl.com/Sanchez-lab-IMPPC
http://www.imppc.org/resources-and-services/genetic-diagnostics-metabolism-disorders/index.html
http://www.imppc.org/gif/web/
www.carrerasresearch.org
Summary of project summary or current research lines (less than 300 words).
Genetic diseases of iron metabolism are a heterogeneous group of rare diseases that
range from microcytic congenital anemia to non-HFE hereditary hemochromatosis. Our
group performs molecular biology studies and genetics of rare diseases of iron
metabolism in order to improve our knowledge and to establish new and better
diagnostics and treatments for these diseases.
Our patients are recruited through the Genetic Unit Diagnostics in Iron Metabolism
(D·IRON), the Iberian Group of Iron Diseases (GIF, Grupo Ibérico de Ferropatología)
and our international collaborations with researchers and associations of patients.
The project involves the sequencing of iron metabolism genes in patients, the set-up of
sequences for new candidate gene and we will address the functional characterization of
new genes using biochemistry and molecular and cellular biology methods.
The identification of the specific genetic cause underlying rare diseases of iron
metabolism allows the establishment of guidelines for the early diagnosis and
preventive treatment, avoiding health complications and dramatically improving the
quality of life of these patients.
58
Project Supervisor:
Name: Ron Schuyler
Group: Bioinformatics Development/Statistical Genomics
Institution: CNAG
email: ron.schuyler@gmail.com
Project Title:
Identifying mutated genes in cancer using WGBS data
Summary:
In the development of cancer, tumor suppressor genes commonly become inactivated
by somatic mutation or aberrant DNA methylation. Whole genome bisulfite sequencing
(WGBS) is used to determine methylation differences between tumor and normal
samples, but standard pipelines for identifying somatic mutations are unable to handle
bisulfite converted reads, requiring a separate sequencing run. However, somatic
variants may also be determined directly from WGBS data.
Although the germline genome of any individual differs from the reference genome by
roughly 10 million single nucleotide variants, and tumors are likely to possess many
more mutations, the vast majority of these differences have no functional impact. On
average, a normal human genome carries only 10-20 non-sense mutations (those
which result in a premature stop codon), and most of these occur in genes which are
dispensable for normal function (such as olfactory receptors). However, cancer driver
mutations are enriched for non-sense and non-synonymous mutations, making it
possible to prioritize those mutation most likely to be involved in cancer development.
Identifying somatic mutations as well as differential methylation from the same dataset
would result in more efficient usage of the WGBS data currently being generated to
investigate the etiology of cancer.
Project goals
1. Identify differences from a reference sequence in WGBS data which result in
nonsense
mutations.
2. Use existing tools to annotate and prioritize other mutations with likely functional
impact.
Expected skills:
-Experience with a high-level programming language (R, C, C++, perl or similar) or
strong shell scripting skills (awk, bash, etc…)
-Some familiarity with cancer biology or sequence variant annotation tools such as Sift
or Annovar would be helpful, but not required.
Possibility of funding:
None.
59
Project Title:
EXOME SEQUENCING OF MDS PATIENTS WITH DELETION 5Q
Project supervisor (besides the name, title and position, please include the
relevant contact information: e-mail, phone postal address, and webpage).
Name: FRANCESC SOLE/TANIA VAVOURI
Group: MDS GROUP
Institution: INSTITUT JOSEP CARRERAS
email: fsole@carrerasresearch.org
web page: http://www.carrerasresearch.org/en/
Summary of project summary or current research lines (less than 300
words).
Our group is focused on research on the Myelodysplastic Syndromes (MDS), a set of
hematological conditions with a high frequency of progression to Acute Myelogenous
Leukemia (AML). As part of one of our current lines of research, we are performing
whole exome sequencing of a subgroup of patients with deletion of chromosome 5q.
Some of these patients are treated with lenalidomide, a MDS drug treatment that we
are also working on. Exome sequencing is performed at CNAG in Barcelona. The
student will be co-supervised by Francesc Solé and Tanya Vavouri and his/her role will
be to analyse the exome sequencing data that we are currently generating in order to
contribute to our understanding of the patterns of mutations of MDS patients and also
those mutations that may predict response to lenalidomide treatment.
At the end of the project, there will be possibility and funding for the student to continue
working in the group as a bioinformatician or predoctoral researcher.
This project is funded by the following grants:
“Mutational analysis (NGS) in MDS 5q- and non 5q- patients treated with
Lenalidomide. Relation with their response to treatment". PI: F. Solé
(IJC). Celgene International.
2.014-2.016. Ref. GRANT-ESP-025_Dr
Sole.
"Combined application of conventional cytogenetics, FISH, SNP arrays
and NGS technology in the clinical practice of Myelodysplastic
Syndromes. Diagnostic, pathogenetic, prognostic and therapeutic
implications". PI. Francesc Solé (IJC). Fundación Carreras Alemania.
Josep Carreras Stiftung. Ref. AR 14/34. 2.014.2.016.
Proyecto de Investigación FIS Instituto de Salud Carlos III. Ministerio de
Ministerio de Economia y Competividad. “Estudio en subclones de los
cambios genéticos de pacientes con síndrome mielodisplásico (SMD)
5q- tratados con Lenalidomida”. PI. F. Solé. Equipo Investigador: Mar
Mallo, Laura Palomo, Silvia Marce, Javier Grau, Blanxa Xicoy. Ref: PI
14/00013. 2.015-2.017.
60
Project Title: Identification of the gate for zinc influx in T lymphocytes
Project supervisor (besides the name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
Rubén Vicente García , PhD
Grup de Fisiologia Molecular i Canalopaties
http://www.upf.edu/fisio/
Departament de Ciències Experimentals i de la Salut (CEXS)
Universitat Pompeu Fabra
Parc de Recerca Biomèdica de Barcelona
C/ Dr. Aiguader, 88
08003 Barcelona, Spain
Tel: + 34 93 316 08 54
e-mail: ruben.vicente@upf.edu
Summary of project summary or current research lines (less than 300 words).
Zinc is an essential mineral for the human physiology. Deficiency in this metal
causes impairment in body growth, neurological disorders and
immunosuppression, leading to morbidity and an increased infection rate.
Nutritional supplementation of this element not only improves hypozincemia but
it is also commonly used as a preventive treatment in front of common
diseases. However, there is no clear knowledge of the biological bases of this
treatment and in certain cases adverse effects have been described. Zinc is a
common structural component of proteins but recently free zinc cellular signals
have been described to influence several signaling cascades and cellular
transcription programs promoting the idea of zinc as a second messenger.
Despite the strong impact the zinc has on the immune system, there are no
clear mechanisms of how this element enters these cells and exerts its effect.
This lack of knowledge is even more striking in T lymphocytes since it is known
that zinc deficiency dramatically alters T cell maturation, influences Th subsets
polarization and impairs cytokine production. The aim of this project is to identify
the gate of zinc entry in T cells in order to have a better understanding of the
function and regulation of zinc in these cells.
The molecular identification of the transporter responsible of zinc entry in T
lymphocytes will provide new strategies for the pharmacological modulation of
these cells not only in cases of zinc deficiency but also in other alterations.
Methodology: Molecular biology, flow cytometry and light microscopy
monitoring fluorescence probes.
61
Project Supervisor:
Name: Josep Vilardell
Group: pre-mRNA splicing and gene expression
Institution: IBMB
email: josep.vilardell@ibmb.csic.es
web page: http://www.ibmb.csic.es/home/jvilardell
Project Title : Modulation of pre-mRNA splicing
Summary: We are monitoring how splicing adapts to major changes in the organism,
such as development or disease. For this we have started by doing in silico analyses of
high throughput data that are being generated by several consortiums. In this context
there are many opportunities for those with a strong motivation to document genomic
strategies based on RNA or epigenetics that control the transcriptome. The final aim is
to approach the molecular basis of our observations. In addition, we analyze how small
genomes, like those of several unicellular fungi, adapt their intronic structure and
splicing machinery to their life style. Given the evolutionary conservation of splicing,
this is relevant to metazoans (including us). This area is of potential interest to
individuals wishing to gain experience on molecular biology, with a focus on molecular
mechanisms of pre-mRNA splicing, and with a desire to explore diverse model systems
(yeast and human cells).
References:
Gupta, V. and J. R. Warner (2014). "Ribosome-omics of the human ribosome." RNA 20: 1004-1013.
Bitton, D. A., et al. (2014). "LaSSO, a strategy for genome-wide mapping of intronic lariats and
branch points using RNA-seq." Genome Res 24(7): 1169-1179.
Acuna, L. I. and A. R. Kornblihtt (2014). "Long range chromatin organization: a new layer in splicing
regulation?" Transcription 5.
Kawashima T et al (2014) Widespread use of non-productive alternative splice sites in
Saccharomyces cerevisiae. PLoS Genet. 2014 Apr 10;10(4):e1004249.
Zhang, J. and J. L. Manley (2013). "Misregulation of pre-mRNA alternative splicing in cancer."
Cancer Discov 3(11): 1228-1237.
Fu, R. H., et al. (2013). "Aberrant alternative splicing events in Parkinson's disease." Cell Transplant
22(4): 653-661.
Plass, M., et al. (2012). "RNA secondary structure mediates alternative 3'ss selection in
Saccharomyces cerevisiae." RNA 18(6): 1103-1115.
Expected skills:
In addition to a good Bioinformatics background, for the work on multicellular
transcriptomes an ability to integrate diverse data (mutational analyses, epigenetics,
transcriptomics, and others) is desirable. The second project would benefit from an
interest on evolution, gene structure, and protein and RNA modeling.
Possibility of funding:
Depending on several factors we will support the application to external funding.
62
Project Title: Exploring synthetic lethal interactions between PARP and the DNA
damage response in cancer treatment
Project supervisor (besides your name, title and position, please include the relevant
contact information: e-mail, phone postal address, and webpage).
José Yélamos
Group leader
Cancer Research Program
IMIM-Hospital del Mar
jyelamos@imim.es
Orientative project summary or summary of current research lines. (If you must
include image files or figures, please keep them to a minimum in terms of size and KB).
The cellular genome is continuously exposed to different genotoxic agents and
physiological processes that introduce damage to DNA. This damage is a continuous
threat to genomic integrity and to combat it, cells have evolved mechanisms, termed the
DNA-damage response (DDR), to detect DNA lesions, signal their presence and
promote their repair. Concomitant to the repair of DNA breaks, a rapid signalling
cascade must be coordinated at the lesion site that leads to the activation of cell cycle
checkpoints and/or apoptosis. Aberrations in these mechanisms lead to genomic
instability, a hallmark of cancer cells. Understanding DDR will not only inform our
knowledge of cancer development but might also provide new therapeutic opportunities.
One major challenge is to understand how DDR components interact with each other to
modulate the response. Key DDR-signaling components are the protein kinases ATM
and ATR, which are recruited to and activated by broken-ends or replication protein-Acoated single-strand DNA respectively. Besides phosphorylation, poly(ADPribosyl)ation of proteins, mediated by PARP-1 and PARP-2, has emerged as a critical
mediator of the DDR. We propose to study the functional interplay between poly(ADPribosyl)ation and phosphorylation in the DDR, and investigate the relevance of such
coordination in the context of genomic instability and cancer. We will use different
cellular and animal models approaches. Understanding the interaction between the
PARP enzymes and ATM and ATR in the DDR is expected to provide a basis for the
identification of new synthetic lethal interaction of relevance in the development of new
therapeutic strategies to treat cancer patients.
63