Objective The endosomal sorting complex required for transport (ESCRT) is a multi-protein complex, which facilitates many processes in biological cells. In particular, it is central to trafficking of membrane proteins and budding of certain enveloped viruses such as HIV. Recent experimental data show that certain ESCRT proteins that associate with lipid membranes assemble into polymer-like structures. These protein aggregates, or polymers, act to buckle the membrane locally and, in this way, drive the formation of vesicles. However, the mechanism how they do that remains very much unclear. The objective of our project is to explore theoretical models, which could shed light on this important and complicated process. To start the project, we are going to combine continuum and molecular models for lipid membranes and calculate the energy required for membrane budding and vesicle formation. The later energy should be next compared with the energy of binding of the ESCRT proteins to the lipid membranes. The binding energy can be estimated from the detailed structure analysis of ESCRT components. Comparison of the two energy scales should rule out some of the possible mechanisms of vesicle formation driven by ESCRT. In next stages of the project we want to study the energetically possible processes of vesicle formation by simulating the ESCRT components that act to deform the lipid membranes. Since the ESCRT protein aggregates are of a mesoscopic size, their activity and interactions with the membranes will require multi-scale analysis and leave room form methods development. As the ESCRT still is not a well-studied complex, and a lot of new experimental data on its structure and functions are coming out currently, we believe that the outcome of our project will substantially contribute to the understanding of this 'molecular machinery'. Fields of science natural sciencesbiological sciencesmicrobiologyvirologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural scienceschemical sciencespolymer sciencesnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health scienceshealth sciencesinfectious diseasesRNA virusesHIV Keywords ESCRT biological membranes computer simulations endosomes membrane budding molecular biophysics protein-membrane interactions vesicle formation Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-IOF-2008 - Marie Curie Action: "International Outgoing Fellowships for Career Development" Call for proposal FP7-PEOPLE-IOF-2008 See other projects for this call Funding Scheme MC-IOF - International Outgoing Fellowships (IOF) Coordinator MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV EU contribution € 228 642,37 Address HOFGARTENSTRASSE 8 80539 Munchen Germany See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Administrative Contact Andreas Stockhaus (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data