Developing a new class of anti-amyloid experimental therapeutics in diabetes

The research project revolves around characterising the conformations of Amylin (IAPP) suspected of being involved within the pathology of Type II Diabetes. The research will begin with acquainting the research student with the instrumentation employed to effectively understand the dynamic pre-fibrillar conformers of amylin that can form under various solvents and differing conditions to gain an appreciation of the intrinsic nature of the disordered protein and the different structures it adopts on both fibrillar and non-fibrillar pathways.

Once the conformations of aggregation and non-aggregation intermediates have been identified, work will proceed to identify how to direct Amylin from the supposed pathological aggregation pathway toward the non-aggregation pathway via the analysis of potential small molecule binding partners (which may be designed utilising organic synthesis approaches at the bench), peptides (which may be cultivated using synthetic biology methods) and other entities utilising MS techniques.

This research will ideally pave the way toward novel inhibitors for aggregation intermediates identified as the cytotoxic agents implicated in the pathology of Type II Diabetes firstly with in vitro promise. After assessing the promising compound(s) pharmacokinetic/pharmacodynamic parameters and druggability as well as any potential for secondary pharmacology, there may be potential to move forward to testing the compound in vivo using a transgenic murine strain expressing human Amylin, where a Type II Diabetic phenotype may be induced in control and compound treated batches to assess the effects of the novel inhibitor.