Objective The objective of this proposal is to probe in aqueous solution protein complexes which are both heterogeneous and possess highly variable stoichiometries. The study of heterogeneous protein systems by conventional means is very challenging since most current biophysical methods perform best for pure solutions of isolated components - yet proteins exert in the majority of cases their biological functionality through forming complexes. We propose in this application that the key to study such systems is to operate in much smaller volumes than in conventional biophysical experiments. We will use microfluidics to obtain information about the physical properties of protein complexes in real time through quantitative micron-scale measurements of mass transport of molecular species under the action of diffusion and electric or centrifugal fields. Furthermore, by working in small volumes, we will study nucleation phenomena inherent to many protein self-assembly phenomena on the level of single nucleation events by segregating individual nuclei into spatially distinct compartments. Modern microfabrication techniques that allow for the manipulation of liquids on the picolitre scales required for this project are available and will be exploited, but the potential of this technology to define experimentally highly heterogeneous protein complexes in terms of their key fundamental physical properties, such as the hydrodynamic radius, charge and mass, and shed light on the physical basis of protein self-assembly, have remained unexploited. Using this approach, we will explore biological problems of fundamental and practical importance characterised by heterogeneity, including functional chaperone complexes, formation and detection of amyloid oligomers and studies of complex biomolecular mixtures. This programme will deliver fundamentally new approaches to study heterogeneous protein complexes and will shed light on the physical principles that govern protein self-assembly. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesbiophysics Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-PE3 - ERC Starting Grant - Condensed matter physics Call for proposal ERC-2013-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE EU contribution € 1 499 895,00 Address TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge United Kingdom See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Administrative Contact Renata Schaeffer (Ms.) Principal investigator Tuomas Pertti Jonathan Knowles (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE United Kingdom EU contribution € 1 499 895,00 Address TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Administrative Contact Renata Schaeffer (Ms.) Principal investigator Tuomas Pertti Jonathan Knowles (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data