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Membrane Regulation of Cell Permeability and Protein Function

$479,957FY2011BIONSF

University Of California-Davis, Davis CA

Investigators

Abstract

Intellectual Merit Biological membranes mediate biological activity by providing an interface for cell-surface recognition, signaling, and transport. One cannot understand cellular function without understanding membranes. They are both the gateways into cells and home to a range of proteins with critical functions (pumps, channels, carriers, receptors, enzymes and energy transducers). Prof. Allen is developing rigorous computational approaches, in concert with experiments, to describe the physical rules underlying biological membrane permeability and membrane protein activity. His laboratory is unveiling the mechanisms of membrane deformations and permeation by ions, charged peptides and ionophores for improved understanding of the actions of viral, toxin and antimicrobial peptides, as well as for the development of novel drug delivery and bio-sensing applications. Prof. Allen has also devised a realizable strategy, employing peptides as model trans-membrane protein segments, to calculate the effects of lipid composition and pharmacological agents on protein activation, and is exploring the regulation of ion channel proteins, crucial to our nervous systems. Broader Impacts This project is providing molecular-level understanding for critical biological functions that will assist in future pharmacological and biotechnological innovations. The quantitative descriptions of protein-membrane interactions emerging from this research are needed to understand the distribution, folding and function of membrane-proteins, which make up nearly a third of the human genome and two thirds of all drug targets, as well as the actions of viruses, toxins, antimicrobial agents and nanodevices for drug delivery and to probe cells at the molecular level. Prof. Allen is actively seeking new and exciting ways of harnessing the curiosity and enthusiasm of young and underprivileged students. He is introducing biomolecular simulation into the undergraduate and graduate curriculum, setting up an educational framework for future generations. He is creating his own initiatives, including the training event SYLICCO (SYmposium on Learning and Industry targeting Computational Chemistry Opportunities), for students to learn the skills of computational chemistry and biophysics and lead them to careers in academia and industry. He is providing opportunities for students from disadvantaged backgrounds, including the development of, and participation in regional outreach and high school programs (e.g. COSMOS, Young Scholars, ACS Seed and Explorit). Prof. Allen is committed to enhancing the UC Davis environment for outreach education, taking this NSF funded science to the grass roots of the community to provide students with exciting opportunities in biomolecular science. This project is funded jointly by the Cellular Process Cluster and the Biomolecular Dynamics, Structure, and Function cluster.

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