Anslaget vid Stockholms unversitet
2014-08-15
Dnr SU FV-4.2.3-2250-2258-14
Dok nr 1
Nine PhD positions at the Department of Biochemistry and Biophysics
Reference numbers SU FV-2250-14, SU FV-2251-14, SU FV-2252-14, SU FV-2253-14,
SU FV-2254-14, SU FV-2255-14, SU FV-2256-14, SU FV-2257-14, SU FV-2258-14.
Deadline for application: September 5, 2014.
The Department of Biochemistry and Biophysics is mainly located with the other Departments of
Chemistry and Life Sciences in the Arrhenius Laboratories for Natural Sciences, which are situated in
the northern part of the University Campus at Frescati. Presently more than 200 people are working at
the department of which around 80 are PhD students engaged in internationally highly recognized
research covering a broad range of subjects. The research projects span across a broad range of topics
covering various aspects of structure and function of biological systems. A majority of these topics
are centered around biological membranes, where many groups working within this area are part of
the Center for Biomembrane Research, which is hosted by the department. The Science for Life
Laboratory is also closely linked to the department. The combination of the highly interdisciplinary
expertise and research projects at the department is unique in Sweden and also at an international
level. This expertise ranges across cell biology, biochemistry, biophysics and theory. For more
information about the department, see www.dbb.su.se.
The open PhD positions are listed below together with a project description and some practical
information regarding the application.
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Ref. No. SU FV-2250-14
Project title: Studies of alternative splicing
Project leader: Arne Elofsson, arne@bioinfo.se, http://bioinfo.se/
Alternative splicing is a phenomena that is widespread among higher eukaryots. However, it is still
not well understood what fraction of the spliced variants are functional in a cell at the protein level. In
this project we will use data from various experimental resources, inlcuding RNA-seq and proteomics
to try to estimate this.
To the application form for this position
Ref. No. SU FV-2251-14
Project title: Development and application of in situ sequencing technology
Project leader: Mats Nilsson (mats.nilsson@scilifelab.se),
http://www.dbb.su.se/en/?p=researchgroup&id=237
Expression profiling is a long established way of measuring molecular states cells and tissues. For
tissues, the expression profile will provide mixed information about the cellular compostion of the
tissue and the states these cells are in. To better understand normal and disease states of tissues,
expression studies should ideally provide single-cell resolution and information about the location of
the cells relative to each other in the tissue.
Stockholms universitet
106 91 Stockholm
2(8)
This project aims to develop technology based on multiplex padlock probing and RCA to achieve
expression profiling of individual cells in the preserved context of fixed tissue sections. The project
builds on previous work where we have developed technology to measure the expression of a handfull of genes in fixed cells and tissue.
The project involves development of experimental and computational procedures and the candidate
should have an M.Sc in biotechnology, or a related field. A solid experimental experience is required
for this position and computer programming and bioinformatics skills are merits.
To the application form for this position
Ref. No. SU FV-2252-14
Project title: Interactions between viral and bacterial cell envelopes at the host interface
Project leader: Rob Daniels (robertd@dbb.su.se),
URL: http://www.dbb.su.se/en/?p=researchgroup&id=31
Respiratory infections are generally a manifestation of co-infections, rather than the initial causative
agent. Respiratory pathogens such as influenza A viruses (IAVs) are well-documented to predispose
individuals for secondary bacterial infections with Streptococcus pneumoniae, however the current
rationale for this specific relationship remains highly speculative. To date, respiratory pathogens are
often studied independently, or in co-infection settings where only one pathogen is altered. The goal
of this project is to genetically and mechanistically define the synergistic interactions between IAVs
and S. pneumoniae and how these networks are affected by changes in the human respiratory
epithelium. These studies will require the student to perform a significant amount of bacterial and
viral reverse genetics and to develop quantitative biochemical assays to examine the interactions
between these two pathogens using a human respiratory epithelium system. Applicants with
interdisciplinary backgrounds in medicine, biochemistry and cell and molecular biology, as well as
experience in molecular biology techniques, tissue culture, microbiology, and microscopy are very
welcome.
Please include a short (up to 1 page) motivation letter, CV, diplomas, and up to three references in
your application.
To the application form for this position
Ref. No. SU FV-2253-14
Project title: Biogenesis of mitochondrially encoded proteins
Projectleader: Martin Ott (E-mail: martin.ott@dbb.su.se, Tel: +46-8-162461)
http://www.dbb.su.se/en/?p=researchgroup&id=106
The respiratory chain of mitochondria allows eukaryotes to use oxidative phosphorylation as a highly
efficient way to generate ATP. The complexes driving oxidative phosphorylation are a mosaic of
proteins encoded by the nuclear and the mitochondrial DNA. Therefore, assembly of the respiratory
chain and the ATPase requires not only expression and import of many nuclear encoded proteins but
also translation of mitochondrially encoded proteins. The mitochondrial genetic system is responsible
for replication and transcription of the mitochondrial genome and for the synthesis of eight
polypeptides within the organelle. Any problems occurring in the expression of the mitochondrially
encoded proteins can impair oxidative phosphorylation and provoke severe human diseases. In our
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group, we use baker´s yeast as a model system because it allows the combination of powerful genetics
with well-defined biochemistry. In this project, we aim to elucidate molecular mechanisms underlying
translation in mitochondria with a special focus on coupling between synthesis and assembly of
respiratory chain subunits. We employ a large variety of cell biological, biochemical, structural and
molecular biology methods. For more information, please visit our website or contact me via phone or
E-mail.
The successful candidate should have a M.Sc. in biology, biophysics or biochemistry. Previous
experience in protein biochemistry, yeast genetics or molecular biology is desirable.
Please include a short motivation, a CV (plus diplomas and certificates/date when you expect to finish
your studies), and the contact details of at least two references in your application.
To the application form for this position
Ref. No. SU FV-2254-14
Project title: NO and O2-reduction mechanisms in bacterial NO-reductases and model
complexes
Project leader: Pia Ädelroth (piaa@dbb.su.se), Tel: 08-164183,
http://www.dbb.su.se/en/?p=researchgroup&id=158
Heme-copper oxidases (HCuOs) catalyze the reduction of oxygen to water (O2+4eout-+8H+in
2H2O+4H+out) in the respiratory chain in mitochondrial and bacterial membranes. HCuOs contain a
heme and a copper (CuB) ion in the catalytic site. HCuOs conserve the free energy from O2-reduction
by generating a proton electrochemical gradient across the membrane in which they are situated.
Bacterial NO-reductases (NOR) also belong to the HCuO family, although they reduce NO to N2O
(2NO+2e-+2H+N2O+H2O), a key step in the nitrogen cycle. NORs contain a non-heme iron (FeB)
instead of CuB, and in stark contrast to the O2-reducing HCuOs, they generate no proton gradient.
We are collaborating with Professor Lu’s group at University of Urbana-Champaign, USA, where
several models of HCuO and NOR active sites have been constructed based on the stable sperm whale
myoglobin (swMb) heme protein. One challenge has been to reduce O2 under mild conditions without
producing reactive oxygen species (ROS). The ‘native’ HCuOs are very efficient at O2-reduction
without releasing ROS, but the mechanism for it is difficult to study due to the complexity of these
proteins. In Lu’s lab, first histidines were introduced in the heme pocket of swMb, forming a Cubinding site (called CuBMb). Then, a Tyr next to one of the His ligands in CuBMb was introduced, and
this artificial enzyme can efficiently reduce O2 to water with very little ROS release. Also, a
functional model of NOR was made by introducing two Glus and three His in the swMb. This protein
binds iron, mimicking the FeB site in NOR, and further shows NOR activity. This NOR model is thus
a simpler and more well-defined system to address important questions. We will study the new swMb
models of the O2- as well as the NO-reducing HCuOs using the so-called flow-flash technique, which
we have used extensively in the past for the native enzymes. These studies are expected to provide
insight into the reaction mechanisms, the mechanism for minimising ROS and the conversion from
O2- into NO-reduction in these important enzymes.
The Ph.D. project involves working with both the native HCuOs as well as the Mb models and
involves a broad range of biochemical and biophysical techniques, including site-directed
mutagenesis, protein purification, membrane protein techniques such as liposome/nanodisc
reconstitution and transient kinetic studies using e.g. laser-induced optical spectroscopy.
To the application form for this position
4(8)
Ref. No. SU FV-2255-14
Project title: Structural dynamics and allosteric regulation of SLC transporters
Project leader: David Drew (E-mail: ddrew@dbb.su.se)
http://www.dbb.su.se/en/?p=researchgroup&id=219
Solute carrier (SLC) transporters are the targets for many therapeutics and they often play a major role
in drug pharmacokinetics. Understanding the mechanisms by which SLC transporters shuttle and
move ions, drugs, and natural compounds across membranes is of fundamental importance. Because
of the technical difficulties in working with membrane proteins our structural understanding is very
limited. The goal of my research is to investigate the alternating access-mechanism of SLC
transporters which are critical to cell homeostasis and their dysfunction is associated with human
diseases, such as cancer and cardiovascular heart disease. The focus on this PhD project will be to use
recent crystal structures to design biochemical and biophysical approaches, such as FRET, to
elucidate the conformational transitions of several SLC transporters in a model membrane bilayer. We
further aim to explore the structural basis of how these SLC transporters can be allosterically
regulated using X-ray crystallography and single-particle cryo EM.
This is a multidisciplinary project and the successful candidate should have a M.Sc. in biology,
biophysics or biochemistry. Experience in biophysics and cell biology is not a prerequisite but an
advantage.
Please include a short motivation, a CV (plus diplomas and certificates/date when you expect to finish
your studies), and the contact details of at least two references in your application.
Publications:
1. A two-domain elevator mechanism for sodium/proton antiport. C. Lee , H.J. Kang, C. von
Ballmoos, S. Newstead, P. Uzdavinys, S. Iwata, O. Beckstein, A. Cameron, D. Drew. Nature
(2013) 501:573-577.
2. Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT. N.J. Hu,
S. Iwata, A.D. Cameron, D. Drew. Nature (2011) 478, 408-411.
3. Benchmarking membrane protein detergent stability for improving throughput of highresolution X-ray structures. Y. Sonoda, S. Newstead, N. Hu, Y. Alguel, E. Nji, K. Beis, S.
Yashiro, C. Lee, J. Leung, A.D. Cameron, B. Byrne, S. Iwata, D. Drew. Structure (2011) 19,
17-25.
4. GFP-based optimization scheme for the overexpression and purification of eukaryotic
membrane proteins in Saccharomyces cerevisiae. D. Drew, S. Newstead, Y. Sonoda, H. Kim,
G. von Heijne, S Iwata. Nature Protocols (2008) 3:784-798.
5. High-throughput fluorescent-based optimization of eukaryotic membrane protein
overexpression and purification in S. cerevisiae. S. Newstead, H. Kim, G. von Heijne, S
Iwata, D. Drew. Proceedings of the National Academy of Sciences USA (2007) 104:1393613941.
To the application form for this position
5(8)
Ref. No. SU FV-2256-14
Project title: Refinement of Ion Channel Structural Changes from Low-Resolution Data
Project leader: Erik Lindahl (E-mail: erik.lindahl@dbb.su.se)
http://www.lindahllab.org/
Ion channels and transporters are critically important membrane proteins that undergo conformational
transitions in order to transport small molecules such as ions along or against a concentration gradient
across cellular membranes. Ligand-gated ion channels are responsible for the fast neurotransmission
across the synapse and open in response to neurotransmitters, but they are also the target of allosteric
modulator compounds such as alcohol, anesthetics, and benzodiazepines. As recently as this spring,
the two first structures of mammal ligand-gated channels receptors were determined, but since these
structures just represent one out of several states (many of which are transient) it has still not been
possible to understand how the gating and allosteric modulation of these channels works, which is
imperative for successful drug design.
The goal of this project is to apply bioinformatics and molecular simulation techniques in
combination with low-resolution experimental data such as CryoEM or residue contact restraints
between subunits to refine both alternative states and the conformational transition pathways in
particular of the gamma-butyric acid (GABA) receptor ion channel. Strong candidates are likely to
have a background in biophysics, bioinformatics or translational medicine.
Please include a short motivation, a CV (plus diplomas and certificates/date when you expect to finish
your studies), and the contact details of at least two references in your application.
To the application form for this position
Ref. No. SU FV-2257-14
Project title: Projekttitel: Prediction of membrane protein complexes
Project leader: Arne Elofsson, arne@bioinfo.se, http://bioinfo.se/
Membrane proteins are the gateways to the cells and as such they are of great importance for the
development of drugs. In addition membrane proteins are quite difficult to handle experimentally,
therefore prediction methods are important to gain information about these protein. We have in recent
years developed a number of state of the art prediction tools (SPOCTOPUS, SCAMPI etc) for
membrane proteins as well as studied structural and evolutionary features of these.
Our ultimate goal is to develop method that can be used to predict the structure of membrane proteins
and in particular of large molecular complexes such as the TOM complex responsible for proteins
import into the mitochondria. To obtain these goals we are combining experimental and theoretical
studies in close collaboration. This position is for the theoretical part of the project. Here we combine
different machine learning techniques (SVM, ANN, HMMs) with biological knowledge in innovative
ways.
A general interest in protein, programming and machine learning methods and a solid background in
bioinformatics, physics or computer science is suitable for this position. Please include the email
adres of two references, examples of source code you have written and a description of why you think
my research is of interest to you. For a full list of publication see http://bioinfo.se/papers/
Publications:
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1) Contreras, F.X., Ernst, A.M., Haberkant, P., Bjorkholm, P., Lindahl, E., Gonen, B., Tischer, C.,
Elofsson, A., von Heijne, G., Thiele, C., Pepperkok, R., Wieland, F. and Brugger, B. (2012)
Molecular recognition of a single sphingolipid species by a protein's transmembrane domain. Nature
481 (7382) : 525-529.
2) Hedin, L.E., Illergard, K. and Elofsson, A. (2011) An Introduction to Membrane Proteins (dagger).
J Proteome Res 10 (8) : 3324-3331.
3) Hennerdal, A. and Elofsson, A. (2011) Rapid membrane protein topology prediction.
Bioinformatics 27 (9) : 1322-1323.
4) Bernsel, A., Viklund, H., Falk, J., Lindahl, E., von Heijne, G. and Elofsson, A. (2008)Prediction of
membrane-protein topology from first principles. Proc Natl Acad Sci U S A 105 (20) : 7177-718
To the application form for this position
Ref. No. SU FV-2258-14
Project title: Network Inference and Systems Biology
Project leader: Erik Sonnhammer, Erik.Sonnhammer@scilifelab.se, http://sonnhammer.sbc.su.se/
at the Stockholm Bioinformatics Center (http://www.sbc.su.se/), which is located at Science for Life
Laboratory Stockholm (http://www.scilifelab.se/) and has excellent contacts with a number of life
science and computer science departments at Stockholm University, KTH, and the Karolinska
Institute. The research project will be supervised by Professor Erik Sonnhammer
(http://sonnhammer.sbc.su.se/).
Cellular mechanisms depend on the complex interplay between proteins, genes, metabolites, and other
components that constitute a living cell. The goal of this project is to develop computational
algorithms and methods that use high-throughput biological data to build networks with details on
how these components interact with each other. This is approached both by building global
association networks of functional coupling (see http://FunCoup.sbc.su.se/) and by Gene Regulatory
Network inference on perturbation-based gene expression data. There is an overlap between these
types of networks which will be exploited in order to improve the quality and usefulness of both.
The methods include regression models, Bayesian integration, various statistical analyses, and inhouse developed modelling techniques. In FunCoup, heterogeneous publicly available highthroughput data sources are combined to predict functional coupling between proteins in order to
build global networks that model pathways and interaction cascades. The FunCoup links can serve as
a prior when inferring regulatory networks in order to limit the search space. We are developing new
algorithms for gene expression based regulatory network inference, for instance for sparsity
optimisation and experimental design. The project involves programming, data analysis,
benchmarking, and modelling, as well as application of the developed methods to experimental data
generated by the group.
The successful candidate should be highly motivated and have an M.Sc. in bioinformatics or related
field, and knowledge of molecular biology. Alternatively, an M.Sc. in molecular biology or related
field and at least 1 year of practical experience in bioinformatics research and programming.
Demonstrable familiarity with sequence and molecular data analysis techniques is essential. Computer
programming (e.g. Perl, Python, R), UNIX skills, and knowledge of biological database systems are
necessary merits.
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The position is for 4 years of full-time study and will administratively belong to the Department of
Biochemistry and Biophysics, Stockholm University. Applications are made on-line, see this file, the
latest on September 50, 2014. For further information about the research project, contact
Erik.Sonnhammer@scilifelab.se
To the application form for this position
_____________
Requirements
To be accepted as a PhD student, credits corresponding to four years of full-time studies at the
undergraduate level are required, including credits corresponding to at least two years of fulltime
studies in chemistry, life sciences or physics, depending on the program. The credits should include
courses at the advanced level (second cycle) corresponding to one year and of these one semester
should be a degree thesis. In order to facilitate the evaluation of merits and suitability for the PhD
studies the curriculum vitae (CV) should contain information about the extent and focus of the
academic studies. The quantity (as part of an academic year) and the quality mark of courses in
chemistry and physics are of particular interest. The title, number of credits and the length in full-time
months of undergraduate thesis and project work, should be specified.
Selection
The selection among applicants will be based on the assessment of their capacity to successfully
complete the PhD program. In practical terms, this means that the study merits will be the main
selection criterion. The local study merits, such as passed advanced courses or project work at the
department, will be given a relatively high weight. Equal opportunity aspects between men and
women will be given a certain weight.
Terms of employment
A PhD education at Stockholm University is four years (48 months). The four-year PhD program
includes at least three years of research and at most one year of course work. The position may be
extended by up to one year if up to 20% teaching assistance or administration is included in the
contract. During the beginning of the PhD education, the student receives a study grant
("utbildningsbidrag"), and after at most one year she/he acquires a PhD studentship
("doktorandanställning"). From July 1st, 2015 employment will be the only option.
The PhD positions are open for international students on equal terms. No tuition fee is charged.
Stockholm University strives to be a work place that is free from discrimination and with equal
opportunities for all.
More information
More information about the project can be provided by the project leader. General information about
the application procedure can be provided by Haidi Astlind (haidi@dbb.su.se). General information
about the PhD training program may be requested from the director of graduate studies, Stefan
Nordlund (stefan@dbb.su.se) or from Lena Mäler, Head of Department (prefekt) (lenam@dbb.su.se).
Faculty of Science: www.science.su.se/english
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Union representatives
Anqi Lindblom-Ahlm (Saco-S) and Lisbeth Häggberg (Fackförbundet ST), telephone +46-(0)8162000 (switch board), and Gunnar Stenberg (SEKO), telephone +46-(0)70-316 43 41.
Application
The application should contain a personal letter (a letter of intent explaining why you are interested in
the specific project, why you are interested in studying for a PhD, what you hope to accomplish during
your PhD studies, and what skills you can bring to this project), a curriculum vitae, a list of two persons
who may act as referees (with telephone numbers and e-mail addresses), copies of degree certificates
and transcripts of academic records, and a copy of your undergraduate thesis and articles, if any.
In order to apply for this position, please use the Stockholm University web-based application form
(where it is possible to select language). The link is found together with each project description
above.
Welcome with your application no later than September 5, 2014.