Protein Dynamics in Complex Environments

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As the protein folding field matures, more complex questions can be tackled. In living organisms, proteins interact with other proteins and nucleic acids, with cellular or extracellular matrices, and with membranes. Fundamental biophysical research is now poised to study this next generation of problems, while maintaining its thrust of using carefully chosen model systems to provide quantitative answers to biological questions. This project will focus on three areas involving biomolecular interactions. A new approach will study the dynamical interplay of folding with protein-protein binding and aggregate formation by designing proteins tethered together so their proximity can be controlled. A second thrust involves the design of membrane protein model systems ranging from simple helices to more complex bundles, to study the interaction of proteins with membranes during folding and insertion. The sequence of processes that lead to stable membrane protein structures will be elucidated in real time. The third area of biomolecular interactions concerns folding of proteins in crowded environments. Proteins dynamics will be studied in highly crowded matrices of proteins and carbohydrates by combining non-fluorescent thermophilic protein matrices with mesophilic probe proteins embedded in the matrix.This research project provides an important link between in vitro and in vivo studies, and a link to computational work on protein-environment interactions relevant to binding, signaling, and survival of proteins in the cell. This is achieved by developing new model systems less complex than the in vivo environment, yet far more complex than in traditional biophysical in vitro studies, and thus within reach of computational biology. Graduate and undergraduate students will receive training at the interface of physics, chemistry and biology, learning by approaches that combine instrumentation, molecular biology, and computational modeling. New US and international collaborations will further enhance the educational value of the research projects. Student-centered research will be complemented by an all-volunteer educational project. The biophysics curriculum at UIUC needs to be re-tooled to meet the needs of students at the interface between biology, instrumentation-oriented physical sciences, and in particular computational modeling, which is now an indispensable part of biophysics. The goal is to create a biophysics and computational biology curriculum for the 21st century, while involving faculty and student volunteers from the ground up. This project is jointly supported by Molecular Biophysics in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences and the Experimental Physical Chemistry Program in the Division of Chemistry in the Mathematical and Physical Sciences Directorate.