Alzheimer’s Disease
Alzheimer’s Disease is caused by the aggregation of the beta-amyloid peptide into toxic oligomers. We design and discover new drugs to interfere with beta-amyloid production and deposition, and reduce its toxicity. For example, we have rationally designed modified peptides to act as inhibitors of beta-amyloid aggregation and toxicity. Drugs are tested with a variety of biophysical and toxicity assays in Manchester, and in vivo by collaborators, to characterise in detail how they work. We are currently screening compound libraries to find new drugs.

Proteomics and Metabolomics
We are using qualitative and quantitative proteomics and metabolomics methods to discover how cells are affected by beta-amyloid. We have found dozens of proteins that respond to beta-amyloid, giving new insights into the biology of Alzheimer’s Disease, and new potential biomarkers and drug targets.
Type 2 diabetes appears to be caused by the toxic amylin peptide killing islets cells in the pancreas that make insulin. We are therefore also seeing how the proteome of cultured islets cells is affected by amylin.

De-Immunising GFP
Green Flurorescent Protein (GFP) is very widely used to report on gene expression. Its use is hindered, however, by causing an unwanted immune response in commonly used mouse strains. We are therefore rationally modifying GFP to remove its immunogenicity while maintaining its fluorescent properties.

Protein Vibrational Spectroscopy
Infra-red, Raman and Raman Optical Activity spectra are rich in information about protein structure. We use bioinformatics methods to determine protein structure from these spectra. We have found that secondary structure contents can be determined to unprecedented accuracy.

Drug Target Proteins
Drug discovery typically requires the identification of protein targets capable of eliciting a desired biological response. We are studying drug target proteins to identify properties that are desirable in human drug targets, considering target proteins for different diseases.
Part of this work requires generating non-redundant sets of proteins, where no two proteins have a pairwise sequence similarity above a set threshold. We generate substantially larger sets than previously used, using novel Graph Theory methods.

Alzheimer’s Disease Alzheimer’s Disease is caused by a small protein called beta-amyloid clumping together, becoming toxic and killing brain cells. We design and discover new drugs to reduce the toxicity of beta-amyloid, in collaboration with our spin-out company, Senexis. We are finding out how beta-amyloid kills cells by measuring how the levels of all the proteins inside a cell change when beta-amyloid is added. This will give new targets for future drugs and help with the diagnosis of Alzheimer’s Disease. Type 2 Diabetes Type 2 diabetes appears to be caused by the toxic amylin peptide killing the islets cells in the pancreas that make insulin. We are therefore also seeing how proteins in cells are affected by amylin. De-Immunising GFP Green Flurorescent Protein (GFP) is very widely used to report on when genes are switched on. Its use is hindered, however, by causing an unwanted immune response. We are therefore engineering GFP to remove its immunogenicity while maintaining its colour. Drug Target Proteins Drug discovery typically requires the identification of protein targets capable of eliciting a desired biological response. We are studying drug target proteins to identify properties that are desirable in human drug targets for different diseases.

Introductory Chemistry

Protein Processing in the Cell

Alzheimer's Disease

Prion Diseases

Protein Folding