Project background:
We recently discovered that about one third of reliably inferred human alternative isoforms may not be expressed as protein. Using EST sequences to infer splicing patterns of known genes, we found that alternative splicing frequently induces premature termination codons in the resulting mRNA transcripts. These mRNAs are thus candidate targets for degradation via nonsense-mediated mRNA decay (NMD), a cellular surveillance mechanism that detects and degrades mRNA transcripts with premature termination codons. Additionally, we found that many of the human alternative protein isoforms in the SWISS-PROT database may not be expressed as protein. Instead, since they derive from mRNA transcripts with premature termination codons, it is likely that these transcripts are degraded by NMD before efficient translation.

Although remarkable progress has been made in the last several years in understanding the cell biology of NMD, many questions remain. We would like to complement and extend our computational results with experiments to address questions about the role and mechanism or alternative splicing coupled with NMD.

Project description:
Our computational screens and pilot experimental work have identified thousands of human alternative isoforms that are likely targets of NMD. We would like to pursue this result in several ways. The postdoc will work with our lab and collaborating labs to experimentally verify and extend this result. The postdoc will use microarrays to test these results globally and more focused assays to directly investigate the fates of select mRNAs.

We would also like to understand the biological implications of coupling alternative splicing and NMD. In many cases, this coupling is unrecognized and potentially very significant. The postdoc will be responsible for designing and implementing experiments that further explore the biology downstream of alternative splicing coupled with NMD.

Finally, we would like to know more about how cells regulate this coupling. To explore this, the postdoc will design and implement experiments that determine the factors involved in specific splicing decisions. Using in vivo and in vitro splicing assays, the sequence elements and trans factors involved will be identified and classified.

The postdoc will be involved in one or more of these aims, along with ongoing computational analyses, according to his/her interests and experience.

Position requirements:
Candidate should have Ph.D. in molecular biology or related field with a strong publication record and strong professional references. The ideal candidate will be an expert experimentalist in some area of RNA biology. Some experience in computational biology is desirable, and an interest in learning more is essential. As this position will involve working with both experimentalists and computational biologists, communication skills and the demonstrated ability to work independently will be weighted heavily.

Salary:
Commensurate with qualifications and experience, within the UC Berkeley postgraduate researcher range of $31,044 - $64,020.

The Berkeley academic environment
The Brenner lab is an interdisciplinary research group, at the University of California, Berkeley, one of the world’s premiere research universities. We are associated with the Department of Plant and Microbial Biology, the Department of Bioengineering, the Department of Molecular and Cell Biology, the Biophysics Graduate Group, and Lawrence Berkeley National Lab. Key collaborators for this project include Donald Rio and Alan Frankel. The University of California, Berkeley is committed to diversity in its staff, faculty, and student body, and invites all qualified people to apply, including minorities and women, veterans and individuals with disabilities.

Interested applicants should send CV, letters of reference, and statement of interest to jobs@compbio.berkeley.edu

For more information, see http://compbio.berkeley.edu/ http://compbio.berkeley.edu/people/ed/rust/