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Postdoctoral Positions in Disease-Associated Defects in RNA Metabolism

Postdoctoral positions are available to study the mechanism by which
nonsense codons elicit mRNA decay in mammalian cells. Nonsense codons,
caused by either frameshift or nonsense mutations, are responsible for
an estimated one-third of inherited genetic diseases. If the resulting
premature termination of translation can be abrogated even slightly so
as to increase the amount of full-length protein synthesized, then the
abnormal phenotypes of many diseases can be abrogated. Therefore, an
understanding of nonsense-mediated decay (NMD) is critical to the
development of clinically useful therapies.

Currently, we are interested in understanding how nuclear pre-mRNA
processing and other nuclear events influence mRNP structure in ways
that impact cytoplasmic mRNA translation and, in so doing, NMD. Studies
will focus on various splicing and translational factors that we have
already found influence, respectively, mRNP structure and NMD in order
to establish how these factors interact and function (see, e.g., Sun
and Maquat, 2000, RNA 6:1-6; Le Hir et al., 2000, Genes & Dev. 14:1098-
1108; Sun, Moriarty, and Maquat, 2000, EMBO J, 19:4734-4744).
Interestingly, some of the translational factors derive from
alternatively spliced pre-mRNAs so that different isoforms may have
different interactive capabilities and, therefore, different roles in
NMD. Having demonstrated that NMD involves a PI 3-kinase-related kinase
signaling pathway, we are currently pursuing studies of the putative
kinase and its modifiers. We are also interested in understanding why
certain nonsense-containing mRNAs are immune to NMD decay as well as
the mechanisms that specify two distinct cellular sites for NMD.

Significant projects are available in molecular biology, biochemistry
and cell biology. Successful candidates will join a well-equipped group
of interactive lab members with diverse backgrounds and expertise in
newly remodeled labs. The University of Rochester is unique for its
sizeable community of RNA researchers and its interest in clinical
approaches to modify disease-associated gene expression by modifying
RNA metabolism.

Be sure to mention you saw this job at Post-Docs.com when you apply.

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