Project period: February – May 2016 

This community previously received Initiator Funding for the project: GW4 Bio X

GW4 community leads

University of Bath: Christopher R Pudney (PI), Ventsi Valev 
University of Cardiff: Dafydd Jones 
University of Exeter: Christian Soeller 

Project overview

We aim to tackle the most fundamental challenge in modern protein science by developing a way to see changes in protein structure and flexibility inside cells. 


It is now common to be able to determine the structure of proteins. However, proteins are highly dynamic and flexible. This flexibility defines much of what they can do and is important for disease states. 

There has been some progress in understanding protein flexibility, but these studies are made on the lab bench rather than on proteins inside cells. There is evidence that the environment inside cells influences the structure and flexibility of proteins. This means that the biomedical relevance of such lab bench studies are questionable as they likely do not represent the natural situation in the body. 

We want to be able to see changes in protein flexibility and structure inside cells. To do this we will build on recently developed microscopy approaches and advances in optical physics to deliver a truly unique technology. Once we have demonstrated the technology we will be able to use it to identify new drug targets and to develop more effective pharmaceuticals. 

Project summary 

The community continued to grow during their Accelerator award, incorporating 7 research groups. The community used the award to fund lab-based research, to establish accurate quantitation of the formation of early stage protein aggregates using a labelling approach compatible with whole cell microscopy experiments. They demonstrated that this approach is able to capture the very earliest stages of protein association and where these aggregates are sub-visible, i.e. the toxic species. The community submitted a paper on their research and applied for grant applications to continue the collaborations instigated during this award.