Dr. Jody Mason, Department of Biology and Biochemistry, University of Bath
Tuesday 26th September, 1.00 p.m., Stacey Lecture Theatre 1
My group focus on design of peptide-based antagonists with high affinity and specificity for inhibiting protein-protein interactions. While forces driving stability are now well understood, much less is known about designing for target specificity. We use Protein-fragment Complementation Assays (PCAs) and alternative systems combined with semi-rational design to select functionally active antagonists of Jun and Fos peptides that can inhibit the oncogenic Activator Protein-1 transcriptional regulator. We have devised a Competitive and Negative Design Initiative (CANDI) technique to increase target-specificity in the PCA system by expressing potential off-targets during selection. Data generated has allowed us to predict coiled coil stability and specificity, and consequently to generate heterospecific coiled coil sets using only on the primary sequence as a design guide. Our screening approach is also being applied to a range of other therapeutically relevant systems that include β-amyloid and α-synuclein implicated in the pathogenesis of Alzheimer’s and Parkinson’s diseases respectively.