Identifying and modulating aggregation propensity in bio-pharmaceuticals (i-CASE)

Biography

I’m working in the Radford and Brockwell labs funded on a BBSRC CASE award in partnership with UCB. I joined Leeds having completed my BSc at Newcastle University.

My Project

My main research focus is protein aggregation with a focus on biopharmaceuticals. Biopharmaceuticals are an important class of therapeutics owing to their high specificity and effectiveness. However, a main problem facing biopharmaceuticals is their propensity to form aggregates, which can occur at any stage during the developmental pipeline. This can be problematic as it can increase cost and time to market, as well as induce adverse immune responses in patients that could potentially be fatal. Therefore, a main challenge facing the biopharmaceutical industry is the ability to identify aggregation-prone sequences as early as possible. My project involves the use of an in vivo assay to detect and quantify aggregation-prone sequences using a simple readout of antibiotic resistance by exploiting TEM-1 β-lactamase. This will be combined with directed evolution methods to evolve less aggregation-prone proteins as well as identify problematic regions of the protein that may contribute to its aggregation behaviour. I will then use various biochemical and biophysical methods to study these proteins and try to elucidate the mechanisms of aggregation as well as explore the relationship between protein sequence and aggregation.