Volné PhD pozice na Ústavu molekulární genetiky AV ČR,v.v.i.
http://www.img.cas.cz/studium/phd-program/
Laboratory of Genome Integrity
www.img.cas.cz/research-groups/jiri-bartek
Research topics: Maintenance of genome stability, oncogene-induced replication stress, RecQ DNA
helicases, R-loops, replication-transcription collisions
DNA damage is a frequent event in the life of a cell. Failure to repair DNA damage can lead to cell
death, while inaccurate DNA repair can give rise to genomic instability, which promotes the onset of
cancer in mammals. Research in our laboratory focuses on understanding various DNA repair
mechanisms operative in mammalian cells. Our main aim is to define the exact DNA transactions
mediated by RecQ DNA helicases, key players in the maintenance of genomic stability. Recently, we
obtained funding from the Czech Science Foundation to study molecular mechanisms underlying the
formation and resolution of RNA:DNA hybrids (R-loops), highly genotoxic structures that can arise as
a consequence of collisions between replication and transcription machineries. This is an extremely
important, but not well understood, aspect of the maintenance of genome stability that attracts
more and more scientists worldwide.
Candidate’s profile (requirements):
M.Sc. (Mgr.) degree or equivalent in biochemistry or molecular/cellular biology, good English,
independent thinking, strong interest in basic research and experimental work
PhD project:
The PhD project will be focused on identification of proteins associated with R-loops under
conditions of chemically- and oncogene-induced replication stress and studying their role in
maintenance of genome stability. The project offers training in a broad range of molecular, cell
biological and biochemical techniques. The student will also undergo short-term trainings at the
Institute of Molecular Cancer Research of the University of Zurich where he/she will be exposed to
front-line research in the field of DNA repair and cancer.
Supervisor: Jana Dobrovolná (jana.dobrovolna@img.cas.cz)
Co-supervisor: Pavel Janščák (pavel.janscak@img.cas.cz)
Laboratory of Cell Differentiation
www.img.cas.cz/research-groups/petr-bartunek
Research topics: Chemical genetics, haematopoietic and neural cell differentiation,
signalling pathways, nuclear receptors
The main interest of the laboratory lies in the molecular mechanism of cell fate
determination. In the lab we have established in vitro systems to study the self-renewal and
differentiation of haematopoietic, neural and mesenchymal stem cells. We use growth
factors and small molecules as tools to manipulate these systems. More recently, we have
initiated more systematic search for such tools using chemical biology/genetics approaches.
Candidate’s profile (requirements):
MSc or equivalent in molecular and developmental biology.
PhD project 1:
Dissecting hematopoietic development using zebrafish model
Supervisor: Petr Bartůněk (bartunek@img.cas.cz)
PhD Project 2:
Nuclear receptors in normal and cancer cells: Identification of new ligands
Supervisor: Petr Bartůněk (bartunek@img.cas.cz)
PhD Project 3:
Mouse transgenic models for sterol-sensing domain containing proteins
Supervisor: Petr Bartůněk (bartunek@img.cas.cz)
Laboratory of Leukocyte Signalling
www.img.cas.cz/research-groups/tomas-brdicka
Research topics: Csk-anchoring proteins in the regulation of leukocyte signaling.
Transmembrane and intracellular adaptor proteins: their roles in signal transduction,
immunodeficiency and leukemia
The Laboratory of Leukocyte Signaling is studying the molecular mechanisms of signal
transduction in leukocytes. Our interest has recently been focused on the regulation of Src-
family kinases by Csk and by receptor tyrosine phosphatases and on the role of Csk
compartmentalization in the process, but the data we generate also lead us to other areas of
signal transduction research. Src-family kinases are tightly controlled enzymes critically
involved in the signaling via a number of leukocyte surface receptors such as T cell and B cell
antigen receptors.
Candidate’s profile (requirements):
M.Sc. or equivalent in immunology, molecular biology or related field.
PhD Project:
The project will be focused on the negative regulation of leukocyte surface receptor
signaling by transmembrane adaprtor proteins. It will include an analysis of mice and cell
lines deficient in the expression of two novel transmembrane adaptor proteins LST1/A and
OPAL1 known to recruit various inhibitory molecules to the proximity of the plasma
membrane. The work will also include a biochemical and structure-function analysis of these
adaptors. During the course of the project the student will acquire a wide range of
techniques required for the analysis of murine immune system functions at the organismal
level, as well as methods employed in the molecular and biochemical analysis of cellular
signaling.
Supervisor: Tomáš Brdička (tomas.brdicka@img.cas.cz)
Laboratory of Biology of the Cell Nucleus
www.img.cas.cz/research-groups/pavel-hozak
Research topics: Cell nucleus, nucleoskeleton, nuclear actin, myosin, microscopy,
ultrastructural methods
The nucleus contains machineries for transcription of genes and processing of RNA products,
and for precise DNA replication, repair and recombination. Nuclear interior is therefore
functionally highly compartmentalized, and the recent evidence points strongly to structurerelated regulation of nuclear functions. Our research concentrates on: (1) the relationship
between nuclear compartmentalization and regulation of gene expression, (2) structure,
dynamics, and function of the nucleoskeleton, which contributes to the nuclear
compartmentalization, (3) functions of nuclear myosins and actin in transcription and gene
expression, (4) functions of nuclear lipids, (5) development of new microscopy methods for
ultrastructural studies.
Candidate’s profile (requirements):
M.Sc. or equivalent in molecular/cell biology, fluent in English
PhD project:
Structure of the cell nucleus related to chromatin remodelling and regulation of gene
expression
Supervisor: Pavel Hozák (hozak@img.cas.cz)
Laboratory of Cell and Developmental Biology
www.img.cas.cz/research-groups/vladimir-korinek
Research topics: Colorectal cancer, Wnt signalling, TCF/LEF transcription factors,
Hypermethylated in Cancer 1, HIC1
The majority of tissues in the adult organism contain a population of tissue-specific stem
cells. These multipotent cells are involved in homeostatic self-renewal and tissue repair
processes. The biology of the stem cells is driven by a limited set of signalling cascades. The
deregulation of these cascades can ultimately lead to the cellular transformation and
formation of tumours. This clearly indicates the connection between the stem cell
physiology and cancer. The scientific goal of the laboratory is to elucidate molecular
mechanisms influencing behaviour of normal and diseased intestinal epithelial cells. Since
the fate of these cells is determined by the so-called Wnt signalling pathway, our main focus
is to find genes regulated by the Wnt pathway and/or encoding proteins directly involved in
the signalling process.
Candidate’s profile (requirements):
M.Sc. or equivalent in molecular, cell and developmental biology or biochemistry; fluent
English.
PhD project:
Title: Molecular mechanisms of tissue homeostasis and tumor formation in the intestine
The aim of the study is to characterize signaling cascades that regulate differentiation of
adult intestinal stem cells or that initiate intestinal tumors and cancer. The intended
methodology will utilize laboratory mouse as a main experimental model. In the course of
the PhD studies the “state-of-the-art” techniques, such as gene knockout or knockin,
transgenesis, high-throughput molecular biology methods, will be employed. Suggested
reading: M. Krausova and V. Korinek: Wnt signaling in adult intestinal stem cells and cancer.
Cellular Signalling, December 2, 2013 (OPEN ACCESS Article).
pii: S0898-6568(13)00363-X. doi: 10.1016/j.cellsig.2013.11.032. [Epub ahead of print]
Supervisor: Vladimír Kořínek (korinek@img.cas.cz)
Laboratory of Transcriptional Regulation
www.img.cas.cz/research-groups/zbynek-kozmik
http://kozmik.img.cas.cz/
Research topics: Eye development and evolution, Pax genes, Wnt/β-catenin signalling
We are interested in the genetic basis of mammalian eye development. Our focus is on the
role of transcription factors and signalling cascades, especially on the role of Pax6 gene,
Wnt/β-catenin signalling pathway and their genetic interaction. A combination of gain-offunction (transgenic) and loss-of-function (conditional knock-outs) approaches is used. Our
second main interest is eye evolution. Early morphological studies have suggested that eye
has evolved multiple times during the course of evolution. In contrast, more recent genetic
data indicate a conserved role of Pax6 and some other transcription factors in eye formation
in a wide range of animals. Several model systems including amphioxus, scallop, medaka and
jellyfish are used in the laboratory to study various aspects of eye evolution.
Candidate’s profile (requirements):
M.Sc. or equivalent in molecular, cell or in developmental biology.
PhD project 1:
Successful applicants will study the role of selected transcription factors (such as Pax6)
during mouse eye development. The following techniques will be applied: Cre/loxP
conditional mutagenesis, phenotypic analysis, advanced imaging, cell sorting, in vitro
differentiation of ES cells, ChIP-seq and RNA-seq.
Supervisor: Zbyněk Kozmik (kozmik@img.cas.cz)
PhD Project 2:
Successful applicants will study evolution of developmental control mechanisms (evo-devo).
Gene-based comparative approach in multiple selected animal models will be used. The
following techniques will be applied: gene isolation, bioinformatic analysis, gene expression
analysis using whole-mount in situ hybridization and RNA-seq, gene perturbation using
transgenesis and programmable nucleases (TALEN, CRISPR/Cas9).
Supervisor: Zbyněk Kozmik (kozmik@img.cas.cz)
Laboratory of Molecular and Cellular Immunology
www.img.cas.cz/research-groups/marie-lipoldova
Research topics: Functional gene mapping, leishmaniasis, atopy
The research programme of the laboratory aims to identify genes and molecular
mechanisms involved in control of immune response and susceptibility to complex infectious
diseases. We focus on complex diseases because they are responsible for the largest part of
human morbidity and mortality and their genetic analysis is subject of an intensive
international effort. They are controlled by multiple genes and hence their pathogenesis
cannot be explained by effects of a single gene with omission of others. Leishmaniasis is such
a complex disease and it has served as a major paradigm of immune response to an
infectious agent.
PhD Project:
Title: Genetic Discovery of Novel Pathways towards Activation of Anti-Infectious Defense
Importance: Leishmaniasis, the disease caused by Leishmania parasites threatens one tenth
of human population. There is currently no efficient human vaccine against the disease and
the treatment causes serious side effects. One of the important factors that influence
susceptibility to this disease is genotype of the infected organism. Numerous potentially
relevant genes were reported, but they explain only part of the observed variation.
Strategy: We were able to dissect complexity of host response to Leishmania, which are
characterized by many immunological and pathological parameters by the use of special
system – recombinant congenic strains of mice and detected and mapped more than 30
novel genes influencing response to Leishmania major and L. tropica. We are characterizing
these genes molecularly and functionally to understand how they work. We are describing
new pathways these genes are involved in using analyses of global gene expression.
Supervisor: Marie Lipoldová (marie.lipoldova@img.cas.cz)
Laboratory of Cancer Cell Biology
www.img.cas.cz/research-groups/libor-macurek
Research topics: Cell cycle, checkpoint, protein phosphorylation, oncogenic transformation
In our recently established laboratory we employ cell biology, molecular biology and
biochemical approaches to identify molecular mechanisms that control cellular responses to
DNA damage. In particular we focus on protein phosphatase PPM1D/Wip1 that plays an
essential role in switching off the DNA damage response pathway, termination of the
checkpoint and control of checkpoint recovery. PPM1D/Wip1 is an important negative
regulator of the tumor suppressor p53. Recent data from transgenic mice and from human
tumors implicate PPM1D/Wip1 as oncogene. Our work aims to decipher molecular
mechanisms regulating function of PPM1D/Wip1 in human cells and in mouse models. In
addition, we use chemical genetics to evaluate PPM1D/Wip1 as a potential pharmacological
target.
Candidate’s profile (requirements):
Eligible candidates should have M.Sc. degree or equivalent in cell/molecular biology or
medicine and show a deep interest in experimental work.
PhD Project 1:
Title: Role of PPM1D/Wip1 mutations in cancer predisposition
Genome integrity of eukaryotic cells is protected by a DNA damage response pathway that
coordinates the cell cycle progression with ongoing DNA repair. In our Cancer Cell Biology
lab we use cell/molecular biology and biochemical techniques to study molecular
mechanisms underlying these events. Recently we have identified novel clinically relevant
mutations in the PPM1D gene that result in production of truncated form of Wip1
phosphatase and severely affect cellular responses to DNA damage. This PhD project will
focus on functional characterization of these truncated Wip1 mutants. We will also use
transgenic mouse models to investigate the oncogenic potential of truncated Wip1 in several
cancer types.
Supervisor: Libor Macůrek (libor.macurek@img.cas.cz)
PhD Project 2:
Title: Role of R2TP complex in DNA damage response and cell cycle control
R2TP complex plays important role in transcription, chromatin remodelling and DNA damage
response. We have recently described that an essential subunit of the R2TP complex protein
PIH1D1 exhibits unique phospho-binding properties. This PhD project will focus on the
molecular mechanisms underlying essential functions of the R2TP complex and functional
characterization of recently identified interacting partners of PIH1D1. We will further
investigate the mechanism of p53 stabilization by R2TP complex and its regulation in context
of the cell cycle and DNA damage response. Suitable candidates should have M.Sc. degree or
equivalent in cell/molecular biology or biochemistry.
Supervisor: Zuzana Hořejší (zuzana.horejsi@img.cas.cz)
Co-supervisor: Libor Macůrek (libor.macurek@img.cas.cz)
Laboratory of Transgenic Models of Diseases
www.img.cas.cz/research-groups/radislav-sedlacek
Research topics: Proteases and their inhibitors, transgenesis, embryogenesis, aging and
epigenetics, neural development
Our department has an exceptional role in IMG, serving as an incubator in which new
research projects and groups as well as research infrastructure (partly core facilities) develop
for the project of BIOCEV. Although thematically distinct, all groups and projects are based
on the usage of mouse models as a tool to reveal gene functions in the complexity of the
whole organism. Proteases in physiology and disease.
Candidate’s profile (requirements):
We are seeking outstanding self-motivated candidates with master’s degree in molecular
biology, physiology, general biology, biochemistry or related fields. We are offering research
at a state-of-the-art equipped institute with experienced colleagues, international working
environment and international collaborations.
PhD project 1:
Title: Research project in E3 ubiquitin ligases.
Regulation of protein degradation via ubiquitination is an important mechanism which was
not thoroughly studied. This system regulates a vast majority of signalling processes and is
therefore very interesting as a potential source of new drug targets. PhD. candidate would
investigate several proteins likely involved in cardiovascular and neural functions, while
using state of the art techniques ranging from cloning, through protein work, transgenic
animal utilization and in vivo experiments.
Supervisor: Radislav Sedláček (radislav.sedlacek@img.cas.cz)
PhD Project 2:
Title: Phenotypic analysis of mice deficient in Farp1
The first knock-out allele for Farp1 has recently been generated by our group. Major focus
will be on liver (healthy vs. challenged models) and intestine. At molecular level, interactions
with TGF pathway and cytoskeletal components determining induction of fibrotic changes
and epithelial barrier function will be addressed.
Supervisor: Radislav Sedláček (radislav.sedlacek@img.cas.cz)
PhD Project 3:
Title: The impact of liver-specific deficiency of plectin on tensional homeostasis and
pathology
We have recently shown that plectin controls keratin cytoarchitecture and cellular stress
response. Based on our preliminary results we hypothesize that plectin confers features of
keratin networks essential for their hepatoprotective function. Major focus will be on
characterizing and comparing pathogenesis of acute, chronic and biliary fibrosis using our
newly generated liver-specific plectin knock-out mouse model.
Supervisor: Radislav Sedláček (radislav.sedlacek@img.cas.cz)
Laboratory of RNA Biology
www.img.cas.cz/research-groups/david-stanek
Research topics: RNA splicing, spliceosome formation, alternative splicing, retinitis
pigmentosa, nuclear structure
Our long-term interest is to determine how cells decode information stored in the genome.
Information in human DNA is fragmented and we study processes and complexes that splice
these fragments together. We focus on molecules called RNAs that serve as information
couriers between DNA and proteins.
Candidate’s profile (requirements):
M.Sc. (Mgr.) degree or equivalent in biochemistry or molecular/cellular biology.
PhD project:
The PhD project will be focused on a role of long non-coding RNA in regulation of alternative
pre-mRNA splicing. Research will include characterization and manipulation of long noncoding RNAs in human cell cultures.
Supervisor: David Staněk (stanek@img.cas.cz)