Details of Grant 

EPSRC Reference:	EP/D002753/1
Title:	Refolding Versus Aggregation in Simple Polypeptides
Principal Investigator:	Curtis, Dr R
Other Investigators:
Researcher Co-Investigators:	Dr JE Magee
Project Partners:
Department:	Chem Eng and Analytical Science
Organisation:	University of Manchester, The
Scheme:	First Grant Scheme Pre-FEC
Starts:	07 October 2005	Ends:	06 October 2007	Value (£):	119,536
EPSRC Research Topic Classifications:	Biophysics Chemical Biology Protein folding / misfolding
EPSRC Industrial Sector Classifications:	No relevance to Underpinning Sectors
Related Grants:
Panel History:
Summary on Grant Application Form
Proteins, the molecules which are the building blocks of living cells,can sometimes stick together in lumps which do not dissolve in water,called aggregates. Some diseases (most famously Mad Cow Disease , orBSE) are thought to be caused by a special kind of aggregate (called afibril) appearing in a living cell. Aggregates are also a problem whenusing a genetically modified bacteria to make a protein (for instance,making insulin-like proteins to help diabetics), where getting theprotein out of aggregates into a useful form can bedifficult. Understanding how aggregates form is therefore very usefulfor biotechnology companies and important for public health, as wellas helping us understand the way that proteins act.It is thought that whether an aggregate will form depends on how sticky a protein molecule is. If it is too sticky, it will fold upon itself, with the sticky surfaces attached to each other on theinside, leaving nothing for other protein molecules to stick to. If itis not sticky enough, it will not stick to other protein moleculeslong enough to form an aggregate. If it does form an aggregate, howsticky it is may change what kind of aggregates are made. Fibrils aremade of precisely arranged networks of protein molecules; if themolecules are very sticky, when they make an aggregate, they will notbe able to move around a lot, and may not be able to rearrange intothe right shape for a fibril.In this project, we will look at how the shape that a protein moleculetakes affects how it can stick to other protein molecules. We willalso look at how protein molecules in aggregates stick to eachother. To do these things, we will use experiments to look at a verysimple type of protein molecule, as well as computer simulations usingboth a simplistic and a detailed model computer for proteins. From theresults, we will try to find principles that link the shape of amolecular to whether a molecule makes aggregates, and use theseprinciples to design mathematical models for how aggregates form.
Key Findings
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Potential use in non-academic contexts
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Further Information:
Organisation Website:	http://www.man.ac.uk