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MetzgerJM_TownsendD

Research Abstracts Online
January 2009 - March 2010

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University of Minnesota Twin Cities
Medical School
Department of Integrative Biology and Physiology

PI: Joseph M. Metzger
Co-PI: DeWayne Townsend

Phylogenetic Analysis of Thin Filament Isoforms

Molecular Modeling of the Troponin Complex

These researchers are using MSI resources for two projects. The first deals with thin filament proteins; different isoforms of these proteins within the context of the heart result in marked differences in the contractile performance. Previous research has shown that critical regulatory domains of these proteins are of utmost importance in influencing this function. The researchers are studying the phylogenetic relationship between isoforms of these proteins across species to understand the relative homology between these isoforms across organisms. This will provide crucial insight into the importance of specific amino acids thus establishing a basis for the conservation or lack of conservation of certain domains throughout evolutionary history. This project uses sequence alignment and phylogenetic trees generated using software available at MSI.

The second, related, project investigates the marked differences in contractile performance of different isoforms like those in the project above. Research has shown that critical regulatory domains of these proteins are of utmost importance in influencing this function. In collaboration with Yuk Sham, Center for Drug Design, these researchers have done molecular dynamics simulations to define the potential interaction interface differences between two different troponin molecules. Further work will be to substitute residues within this interaction domain to characterize the effect on interaction in these simulations. These studies will lead to functional experiments in the future.

Group Members

Joshua Martindale, Research Associate
Nathan Palpant, Graduate Student
Brian Thompson, Research Associate