Temporal and spatial effects on expression and function

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DESCRIPTION (provided by applicant): Despite their importance in nearly all biological processes, the impacts of spatial and temporal effects on gene expression, protein abundance, and protein modification are greatly underrepresented in genome-wide analyses. This proposal is aimed at the development and implementation of new experimental and computational tools capable of measuring and modeling spatial and temporal biological data, focusing on the poorly studied relationship between the cell cycle and mitochondrial function in the model organism, S.cerevisiae. The research plan focuses on experimental systems for the large-scale measurement of mutant phenotype and genetic linkage, whole-genome RNA expression analysis using a system of RNA abundance, quantitation on an absolute scale, and mass spectrometry-based identification of proteins and protein modification states present in subcellular organelles. The computational analysis of this data will include the transcriptional regulatory network under these conditions, a model of yeast metabolism, and the relationship between evolution and organelle function. All of the techniques and methodologies developed in this study are designed to be genome-wide, high-throughput, cost-effective, and readily transferable to other systems. In addition to developing much needed technologies and computational tools, this project will also contribute important biological results that will further our understanding of previously characterized genes and pathways that are likely to be relevant to human disease. The candidate's long-term career goal is the establishment of an academic research laboratory focusing on the analysis of biological problems using a combination of functional genomics and computational modeling of biological processes. The Genome Scholar phase of the award will be used to improve computational skills and to acquire experience in the use of protein mass spectrometry. The Faculty Transition phase of the award will be used to establish a multidisciplinary environment for the conduct of genomics research.