Characterisation of an endotoxin-sensing molecular switch

This project is one of ten (10), four-year PhD Studentships funded by Medical Research Scotland (http://www.medicalresearchscotland.org.uk/funding.htm) and delivered jointly by the named University and Company. The Studentship will provide the first-class academic and commercial training needed to equip the successful student for a science career in an increasingly competitive market.

Characterisation of a molecular switch: how does Factor C recognise, and change shape in response to endotoxin? Towards a sensitive synthetic endotoxin test – delivered by the University of Glasgow and Marine Biotech Limited (http://www.marinebiotechlimited.com).

Academic Supervisors: Dr Brian Smith & Dr Sharon Kelly; Company Supervisor: Alex Muhlholzl

This project, in collaboration with Marine Biotech Limited, will examine the molecular recognition events that underlie the recognition of bacteria by Factor C, the initiator of the Horseshoe Crab’s innate defence system, using structural biology and biophysical techniques. Horseshoe crab blood components are used for the compulsory safety testing of all pharmaceutical injectable products and medical devices. Horseshoe crabs have developed a way of dealing with bacterial infection by recognising endotoxins at the infection site. A protein called Factor C recognises endotoxin and elicits a chain of events which leads to inactivation of the bacteria as well as wound healing. We wish to understand in molecular detail how Factor C recognises endotoxins specifically. This knowledge could be used to develop a synthetic testing system based on Factor C to provide a robust endotoxin detection test. Such properties could also form the basis for development of future therapeutics in endotoxin-compromised patients.
The successful applicant will be a highly qualified and motivated graduate with a life sciences or chemistry degree and relevant experience. They will be trained in molecular biology, recombinant protein expression and purification, structural biology and biophysical techniques. In addition they will have the opportunity to spend a proportion of their time working on-site with the Marine Biotech Limited team gaining experience in commercial biotechnology entrepreneurship. The right applicant will be well placed to join Marine Biotech Limited at the end of their PhD and to develop their business and biology skills in a commercial environment.