Postdocs in comparative genomics, Salk Institute

The Manning lab at Salk has postdoc openings for three bioinformatics projects, leveraging genome sequences to understand fundamental biology. Two of them have strong components of nematode genomics, and the third covers both eukaryotes and prokaryotes. Here’s the full description:

The Razavi-Newman Center for Bioinformatics (RNCB) at the Salk Institute has postdoctoral openings in three areas: exploring the link between aging signaling and neurodegeneration in nematodes and vertebrates, understanding the genomics and evolution of phosphatase signaling, and extreme assembly of bacterial metagenomic fragments to understand the biology and taxonomy of shotgun environmental sequencing projects.

The Salk Institute, perched over the ocean in sunny San Diego, is one of the jewels of biomedical research, having produced almost a dozen Nobel prize winners and with an almost unrivalled concentration of scientific talent. Salk is regularly rated in the world’s top three biomedical research organizations in terms of publications and faculty accomplishments. More institute information is at http://www.salk.edu and the bioinformatics center is at http://bioinformatics.salk.edu. To apply, send CV, list of research interests and reference list, in PDF format, to manning@salk.edu.

Project 1: Systems biology of aging and neurodegeneration.
The recent discovery of a link between aging pathway signaling and neurodegeneration (Cohen et al, Science 313, 1604-10) has opened up a new front in understanding and treating many disease of aging, including Alzheimer’s and Parkinson’s diseases. This has spurred the creation of an interdisciplinary consortium involving leading groups in proteomics, genomics, proteostasis, trafficking, aging and neuropathology, to understand the systems biology of aging and neurodegeneration, and to discover new therapeutic targets. This position offers a key role in that consortium, integrating comparative genomics with high-throughput and focused experimental data, to unlock the mechanisms and logic of age-related signaling and its control of the protein detoxification programs implicated in neurodegenerative diseases.

This position will collaborate closely with the Dillin lab at Salk, (worm and mouse models of aging and neurodegeneration), and with nearby consortium members at the Scripps Institute (Yates: proteomics; Kelly: proteostasis; Balch: protein trafficking) and UCSD (Masliah: neuropathology).

We will use comparative genomics of promoters and proteins, and expression profiling (RNA and protein) to understand the genetic programs downstream of aging-related signaling pathways in C. elegans, to compare these with mammals and other model organisms, and to study their function in animal models of neurodegeneration.

Requirements:
• A strong background in bioinformatics and genomics; in particular, an understanding of computational promoter analysis and comparative genomics, substantial experience in the analysis of gene expression profile data, a robust working knowledge of statistics, and practical competence in Perl/BioPerl or equivalent.

• A background in biochemistry, molecular genetics or model organism research.

• Excellent communication and teamwork skills to take advantage of the highly collaborative environment, adaptability and willingness to contribute to the overall goals of the project and bioinformatics center.

• A passion for innovation, and demonstrated initiative in tackling new areas of research.

Project 2: Evolutionary genomics of cellular signaling
The emerging flood of genome sequences provides a key to unlock the relationship between gene sequence and function, model the mechanisms of protein action, and understand the role of genomic variation in disease. We have worked for several years on the evolutionary genomics of protein kinases (see http://kinase.com), and are now expanding this work to another critical family: the phosphatases, the essential counterpart of the protein kinases. We will use a wide array of custom tools and approaches developed for the kinome to provide a similar understanding of the phosphatome. This will range from looking at the deep evolution of phosphatases in early eukaryotes, to understanding the role of SNPs and somatic mutations in disease by comparisons of orthologous genes from dozens of vertebrate genomes. It will also provide an opportunity to further develop our annotation tools to expand to coverage of complete genomes rather than individual gene families. This work will be in close collaboration with the Dixon lab (UCSD).

Requirements:
• A strong background in bioinformatics and genomics; in particular, an robust understanding of protein sequence analysis, gene prediction and comparative genomics. A working knowledge of statistics and practical competence in Perl/BioPerl are also key.

• A background in biochemistry, signaling, molecular genetics or model organism research.

• Excellent communication and teamwork skills to take advantage of the highly collaborative environment, adaptability and willingness to contribute to the overall goals of the project and bioinformatics center.

• A passion for innovation, and demonstrated initiative in tackling new areas of research.

Project 3: Assembling the microbial metagenome
Metagenomic shotgun sequencing has recently tripled the number of known protein sequences and has huge implications for understanding the diversity of life and in applications to everything from protein engineering to climate change. This project tackles the challenge of building millions of random DNA fragments from diverse microbes into a coherent model to understand the functionality, taxonomy, and diversity of this data.

Specifically, the goal is to assemble metagenomes – mosaic genome segments that come from an assembly of related species rather than one clonal organism, to better understand both the genomic and molecular repertoire of groups of species and the taxonomic distribution of any sample. This will also require an understanding of the rate of evolution of hundreds of conserved gene families and the ability to track horizontal gene transfer and functional shift in the evolution of many bacterial genes. This will build on current work in our group on domain distribution in the Venter Institute GOS project (http://collections.plos.org/plosbiology/gos-2007.php) and the deep evolution of protein domains as exemplified by protein kinase-like kinases. This project will collaborate closely with the Venter Institute and the San Diego-based CAMERA metagenomic database (camera.calit2.net), and with local collaborators at UCSD, the Scripps Institute (TSRI) and the Scripps Institute of Oceanography (SIO).

Requirements. This is a challenging project with the potential for a pivotal impact in the analysis of metagenomic sequence and global understanding of microbial evolution and function. Candidates should have a record in development of innovative research approaches, a strong background in deep sequence analysis, phylogeny and a robust working knowledge of statistics. Strong skills in structured programming, algorithm development or refinement, and database interactions will be required. This project is part of a larger group, and so excellent communication, interpersonal, and team skills will be required. While frequently overused in job ads, the attributes of being strongly self-motivated, determined and capable will be critical for this project. In return, we can offer pioneering knowledge of the field, robust support and guidance, a superb working environment, key collaborators and the opportunity to help define the future of genomics and molecular evolution.