CHRISTINA TYSOE

Christina Tysoe
M.Sc. Program
Previous Degree: B.Sc. Biochemistry/Molecular Biology
2011 Cohort

Human pancreatic α-amylase catalyzes the cleavage of starch into small malto-oligosaccharides, which are then further cleaved to glucose within the gut. Unsurprisingly, its activity has been positively correlated to blood sugar levels and its selective inhibition has shown to be highly effective in controlling blood glucose levels in diabetic and obese animals. Recently, a highly selective and potent inhibitor, Montbretin A, was discovered in a high-throughput screen of biological extracts. While this compound exhibits promising characteristics as a diabetes therapeutic, its complex structure and biosynthesis present a challenge for clinical usage. On the basis of recent structure/function studies I aim to design and synthesize an analogue of this compound that offers similar selectivity and potency while proving to be more easily accessible. I will also be working with the peptide-based HPA inhibitor, RAK01, that was discovered in a parallel screen. While the sequence of this peptide is known, important structural details, such as the location of its disulfide linkages and the importance of individual amino acids, remain a mystery. Unfortunately, after its initial isolation from a marine biological extract, acquisition of more material for study has proven challenging. I plan to express RAK01 as a cleavable fusion protein which can then be analyzed to shed light on this inhibitor’s structure and function.

Supervisor: Stephen Withers