PhD position in evolutionary systems biology (Ref. No. DBB 7-12)
The application should be labelled with Ref. No. DBB 7-12 and received by the Department by March 15 2012 or up until the position is filled.
COMPUTATIONAL ANALYSIS OF GENE AND GENOME DUPLICATIONS IN VERTEBRATES

We are looking for an exceptionally talented and motivated PhD student in evolutionary systems biology to work and study under joint supervision of Dr. Lukasz Huminiecki and Prof. Arne Elofsson at the Department of Biochemistry and Biophysics, Stockholm University.
You will live in STOCKHOLM, a beautiful and international city with high standard of life and social services, the Home of the Nobel Prize, offering a vibrant scientific environment and rich opportunities for collaborations, postdoctoral fellowships, or employment in the technology sector. You will work within the newly created bioinformatics and computational biology cluster at the Science for Life Laboratory in Stockholm (SciLifeLab Stockholm), a joint venture between three of Sweden’s top research universities: Karolinska Institutet, KTH Royal Institute of Technology, and Stockholm’s University (see http://www.scilifelab.se/ and http://www.scilifelab.se/index---php?content=stockholm).

Why is this a good area to study? In the February 11, 2011 special issue of Science, dedicated to data intense science and celebrating the tenth anniversary of the publication of the human genome, the Editors of the magazine called for increased funding and attention given to data storage, sharing and analysis. To quote verbatim from the Editorial: “Science is driven by data. New technologies have vastly increased the ease of data collection and consequently the amount of data collected, while also enabling data to be independently mined and reanalyzed by others”. Calls for a paradigm change in the era of data intense science have also been formulated in an influential industry white paper entitled: “The Fourth Paradigm: Data-Intensive Scientific Discovery”.

GENOME sequencing and computational analysis of omics data generated by the genomics community have great potential to enhance our understanding of the origins and evolution of animals. Nearly ten years after one of the most significant scientific milestones generated for the shared benefit of the humanity: the sequencing of the human genome, a steady stream of additional vertebrate genomes is being processed through the sequencing and annotation pipelines, ensuring a rich supply of data over the next several years. Plans are being made to sequence as many as 10,000 vertebrate species, tens of thousands of individual human genomes, and hundreds of thousands of tumour samples, yet with traditional emphasis in biology on data generation rather than analysis, there is an acute shortage of experts in computational genome analysis.

EVOLUTION is a molecular tinkerer, not a rational designer. All animal genes derive through consecutive cycles of copying and modification, called gene duplication. Our project will focus on computational analysis of global patterns of gene and genome duplications in vertebrates, and their consequences for evolution of cellular systems involved in processing information. In particular, we will focus on signal transduction, and microRNA (miRNA) network evolution, as well as expression pattern evolution (in which cell and tissue-types the gene is switched “on” or “off”). We will use pathway databases and freely available genomic, expression, and miRNA datasets, to infer architectural changes of the animal signal transduction and miRNA networks after small scale duplications (SSDs) and whole genome duplications (WGDs). Quantification of the patterns of nonfunctionalization, subfunctionalization, and neofunctionalization will enhance our understanding of the evolutionary forces driving duplicate retention. Finally, all animals share a small and very well conserved set of genes controlling their development, called “developmental toolkit”. The identification of the shared animal developmental toolkit is one of the most significant and fundamental discoveries in biology, and we designate the toolkit to be a focus area investigated besides the global perspective.

In a broader perspective, translating GENOMICS into knowledge and new inventions will demand integration of diverse scientific fields and methodologies. Genomics is technology-driven and geared for large descriptive catalogs. Bioinformatics is data-driven and technical. Computational biology is abstract and mathematical. Molecular evolution takes a broader view on change and conservation of DNA and protein sequences across taxa. These fields are characterized by different research cultures, languages, and hierarchies of concepts, yet they must be bridged together, for the promise of genomics to be fulfilled. Our proposal links elements of genomics, bioinformatics, computational biology, and molecular evolution to test important hypotheses about vertebrate evolution.

The methodological toolkit necessary for the project will consist of phylogenetics and other molecular evolution methods, R statistical package, Bioconductor, MySQL, and Perl. Unix or Linux experience is highly desired. Candidates will have undergraduate degree background in biology, biotechnology, biophysics, molecular biology, mathematical biology, bioinformatics, mathematics, or computer science. Good command of English is required. This is not a pipeline bioinformatics project: the chosen candidate will have a natural aptitude to flexibly and creatively tackle complex and abstract problems, using a dynamic mixture of procedural programming, SQL, statistics, bioinformatics, and evolutionary theory. If you come from computational background, you will already have an interest in biology, and will be willing to study molecular evolution and read papers in this field. If you come from background in life sciences, you will already have substantial bioinformatics experience, and will be willing to develop your programming and statistical skills further.

REFERENCES:
2R and remodeling of vertebrate signal transduction engine. Huminiecki L, Heldin CH. BMC Biol. 2010 Dec 13;8:146.
(look it up at http://www.biomedcentral.com/1741-7007/8/146)
Emergence, development and diversification of the TGF-beta signalling pathway within the animal kingdom. Huminiecki L, Goldovsky L, Freilich S, Moustakas A, Ouzounis C, Heldin CH. BMC Evol Biol. 2009 Feb 3;9:28.
(look it up at http://www.biomedcentral.com/1471-2148/9/28)
Divergence of spatial gene expression profiles following species-specific gene duplications in human and mouse. Huminiecki L, Wolfe KH. Genome Res. 2004 Oct;14(10A):1870-9.
(look it up at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC524410/?tool=pubmed)

About the Department of Biochemistry and Biophysics, Stockholm University More than 20 research groups are active at the Department of Biochemistry and Biophysics. The research projects span across a broad range of topics covering various aspects of structure and function of biological systems. A major fraction of these topics are centered on biological membranes, where many groups working within this area are part of the Center for Biomembrane Research, which is hosted by the department. Also the Stockholm Bioinformatics Centre and SciLifeLab Stockholm are 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. Some specific topics that are addressed include membrane protein biogenesis, membrane protein topology & assembly, mitochondria & chloroplasts, protein structure & function, protein folding & trafficking, lipid biosynthesis & function, energy conversion, biochemical toxicology, DNARNA-PNA interactions, biological nitrogen fixation, viral membrane glycoproteins, protein structure & disease, bioinformatics, computational structural biology and development of theoretical tools. The experimental studies are performed on a wide range of organisms and are also combined with the use of a wide range of advanced biochemical and biophysical techniques. For more information about the department, see http://www.dbb.su.se.

Further information on the web: Stockholm University: http://www.su.se/english Faculty of Science: http://www.science.su.se The Department of Biochemistry and Biophysics: http://www.dbb.su.se The handbook for postgraduate students: http://www.doktorandhandboken.nu/english
Terms of employment Economic support is guaranteed during the agreed time in the individual study syllabus (study plan) for the graduate studies, totally for a maximum of 4 years.

Be part of the genomics revolution in biology and medicine! Discover secrets of life locked in animal genomes!
 

Administrative Contacts & How To Apply

The application should contain a letter of intent (one to two pages that explain why you are interested in working on this 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), curriculum vitae, copies of degree certificates and transcripts of academic records, a list of two persons who may act as referees (with telephone numbers and e-mail addresses), and one copy of your undergraduate thesis and articles, if any.
email: haidi@dbb.su.se (please combine all your documents into a single pdf file)
cc: lukasz.huminiecki@ki.se

Funding Information

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