This project is a 4 year BBSRC funded PhD studentship to start October 2013, inclusive of a 1 year Masters in Research and a 3 month Professional Internship for PhDs (PIPS) placement at the Darwin Centre of the Natural History Museum. It is a collaboration between the labs of Doryen Bubeck (Division of Molecular Biosciences), Oscar Ces (Chemistry Department), and Xiaodong Zhang (Division of Molecular Biosciences).
Title: Complement-mediated pore formation
The immune complement system in blood kills microbes by making ‘membrane-attack complex’ (MAC) pores in cell membranes. CD59 is a complement regulator that blocks MAC pore formation and protects hosts from bystander damage. Some microorganisms subvert the immune system by hijacking complement regulators to enhance infection. Intermedilysin (ILY) is bacterial toxin that engages CD59 to initiate membrane attachment, the first step in this toxin’s pore formation. The aim of this proposal is to understand a molecular mechanism underlying ILY pore formation and the role CD59 plays in the pathway. Specifically it uses an interdisciplinary approach, integrating structural biology and membrane biophysics, to characterize the assembly of ILY pores in a CD59-decorated liposome model system.
For more details on eligibility and how to apply please see:
Insights into the action of the superfamily of cholesterol-dependent cytolysins from studies of intermedilysin. Polekhina G, Giddings KS, Tweten RK, Parker MW.
Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):600-5.
Mapping the intermedilysin-human CD59 receptor interface reveals a deep correspondence with the binding site on CD59 for complement binding proteins C8alpha and C9. Wickham SE, Hotze EM, Farrand AJ, Polekhina G, Nero TL, Tomlinson S, Parker MW, Tweten RK. J Biol Chem. 2011 Jun 10;286(23):20952-62.