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CAREER: Quantitative analysis of translational regulation

$400,000FY2007ENGNSF

University Of Illinois At Urbana-Champaign, Urbana IL

Investigators

Abstract

Christopher Rao 0644744 High-throughput sequencing has revealed numerous patterns and variations in the genomic architecture of diverse species of bacteria, though this information still cannot be directly compiled into mechanistic models of gene regulation. The objective of this research is to develop computational tools for identifying the general mechanisms involved in translational regulation. Translation plays an integral role in gene regulation yet computational tools for analysis are far less mature than their counterparts in transcription. The specific aims of these experiments are: (1) to determine how the sequence and structure of the translation initiation region affects protein synthesis; (2) to characterize how the active movement of ribosomes facilitates translational coupling between adjacent genes; and (3) to develop stochastic models for simulating translation and mRNA remodeling at single-base regulation in order to make predictions about specific genes and operons. If successful, the proposed research will result in new computational tools for identifying mechanisms involved in translational regulation directly from DNA sequence. These tools will facilitate the development of quantitative models of gene regulation and also lead to rational approaches for the design of synthetic gene circuits. This integrated research and education plan will train both undergraduate and graduate students in the use of computational tools to solve problems in molecular biology. Students will be exposed to a combination of theory, algorithms, and experimentation, providing them with the interdisciplinary training necessary to solve an increasing number of problems in medicine and biotechnology

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