Overall goals of the proposed research are two in number: (1) to continue the development of mass spectrometry instrumentation, software, and methodology for the identification and sequence analysis of proteins in complex mixtures at the attomole/femtomole level and (2) to employ this technology to solve structural problems at the cutting edge of biological research.
Specific aims i nclude: (1) development of automated mass spectrometry instrumentation for the differential display and quantitation of proteins up- or down-regulated in diseased vs healthy cells, organelles, or tissues; (2) continued development of technology for the selective sequence analysis of phosphorylated peptides and proteins; (3) elucidation of the histone code, the pattern of post-translational modifications on the n-terminal tails of histone proteins that regulate transcription, gene silencing, DNA damage repair, chromosome condensation in apoptosis, chromosome segregation during mitosis,etc; (4) development of technology that facilitates systematic identification of all physiologically relevant substrates and their phosphorylation sites for particular protein kinases on a genome wide scale; (5) identification of protein-protein interaction partners of telomerase, the human reverse transcriptase that maintains chromosome length and allows cancer cells to become immortal; (6) identification of proteins differentially expressed in plasma that can be used to predict onset of myocardial infarction; (7) identification of proteins in cerebrospinal fluid that can be used to predict onset of migraine headaches or to serve as targets for therapeutic intervention; (8) identification of proteins differentially expressed by Pseudomonas aeruginosa when grown under anaerobic (cystic fibrosis) vs aerobic conditions; (9) identification of proteins differentially expressed in the hemolymph of mosquitos before and after infection with malaria parasites; (10) identification of proteins that function as diagnostic markers or druggable targets for acute myeloid leukemias; and (11) identification of phosphorylated proteins in the nucleus and mitochondria of HEK cells before and after treatment with several different drugs.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BECM (01))
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Edmonds, Charles G
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University of Virginia
Schools of Arts and Sciences
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