The molecular determinants of the aggregation and toxicity of peptides and proteins

Title of project or programme

Title of PI

Principal Investigators of project/programme grant

Title	Forname	Surname	Institution	Country
Dr	Damian	Crowther	University of Cambridge	UK

Address of institution of lead PI

Institution	University of Cambridge
Street Address	The Old Schools, Trinity Lane
City	Cambridge
Postcode	CB2 1TN

Country

United Kingdom

Source of funding information
Medical Research Council
Total sum awarded (Euro)
1826882.79
Start date of award
01-03-2008
Total duration of award in months
60
The project/programme is most relevant to

Alzheimer’s disease and other dementias
Neurodegenerative disease in general

Keywords

Research abstract in English
This proposal brings together a group of people with a wide range of skills from the Departments of Chemistry, Physics, Nanoscience, Genetics and Medicine to investigate the fundamental causes of a range of diseases that are caused by protein misfolding and aggregation. Our project is based on three key advances that have occurred in Cambridge, the first is the understanding that the potential to form amyloid fibrils is a common, if not fundamental, property of all proteins. The second is the discovery that we can accurately predict the aggregation propensity of proteins knowing only their amino acid sequences. The third advance has been the development of Drosophila models of protein aggregation diseases. We will focus on understanding the fundamental mechanisms that underlie a range of protein misfolding disorders and use our range of skills to carefully observe protein aggregation in the test tube, interpret the data using sophisticated computer algorithms and use Drosophila model systems to provide further insights into pathological significance. We will extend our preliminary studies on the Abeta peptide and investigate other proteins implicated in neurological disorders and so formulate a quantitative model that describes the molecular determinants of peptide and protein aggregation and toxicity. Such a powerful understanding of fundamental disease mechanisms will provide us with new opportunities and strategies for therapeutic intervention.
Lay summary

In which category does this research fall?

Basic research

The molecular determinants of the aggregation and toxicity of peptides and proteins

Investments > €500k
United Kingdom
Alzheimer’s disease & other dementias|Neurodegenerative disease in general
2011