Final Report Summary - MPFP (Membrane protein dynamics and interactions)
Membrane proteins are important for virtually all aspects of life, but are difficult to study experimentally due to their physical properties related to their location in membranes. This grant was used to recruit the membrane protein expert Professor Judith Klein-Seetharaman, from the University of Pittsburgh, USA and retain her in the Division of Metabolic and Vascular Health at the University of Warwick. She used the funds to establish an interdisciplinary research program combining computational and experimental studies, looking at membrane proteins from both, structural and systems biology point of views. In the structural biology project, she investigated membrane protein folding by characterizing denatured states of the model system and G protein coupled receptor mammalian rhodopsin in molecular detail, in comparison to the archaebacterial membrane protein, sensory rhodopsin, in a collaboration with the University of Cambridge. Second, conformational changes in the interferon gamma receptors were studied using circular dichroism, fluorescence spectroscopy and cysteine biochemistry. Third, interactions of proteins with lipids were studied in detail, and unique properties of lipid binding sites on proteins were structurally characterized. Uniquely, protein dynamics was also identified to play a major role in binding. Fourth, lipid-lipid interactions were quantitatively modelled and biophysically characterized in a new collaboration within the Division. In the systems biology project, the predicted human membrane receptor interactome was experimentally validated in a new collaboration with the Chemistry department. Thus, the intended goal of knowledge transfer from her USA research to the University of Warwick was successful at all levels, from initiation of new collaborations in the UK and within the University and Division, to publication of exciting scientific results. Beyond immediate research activities, she also conducted broader impact, education and outreach activities, ranging from disseminating her work in lecture series, conferences, a website, journal publications and through design and implementation of a Master class to conducting outreach activities in local schools and Science Fairs (Skirting Science, Big Bang Fairs) and by founding a local, active chapter for the national organization, ScienceGrrl, to promote women in science.