Prize Studentship Competition. Please see the department’s web page for application details. The closing date for studentships commencing October 2020 is January 10th 2020. We are currently offering two studentships.
1. Novel approaches to enhance glycan immunogenicity for HIV-1 vaccine design (with R. Moore, B. Davis (Chemistry) & Q. Sattentau).
An HIV-1 vaccine is urgently required to eradicate the HIV-1 pandemic. Currently most effort and optimism is focussed on the production of protective neutralizing antibodies by immunization with HIV-1 envelope glycoprotein (Env)-based immunogens. However, despite recent progress, elicitation of antibodies that can neutralize a majority of circulating viral strains has not been achieved. One challenge is the weak immunogenicity of glycans associated with Env, which are targets of many neutralizing antibodies generated in infected individuals. We have used post-translational mosifications to stabilize Env-based immunogens and in this way have enhanced induction of neutralizing antibodies (1-3). The current project is to use novel site-directed post-translational modification strategies to enhance the immunogenicity of selected glycans as a means to target highly conserved regions of Env. This project will use techniques in molecular and structural biology, glycan biochemistry (in collaboration with the chemistry department) and in vitro and in vivo immunology.
2. Mechanisms underlying the immune enhancing properties of aldehydic protein adducts (with Q. Sattentau).
The non-enzymatic adduction of aldehydic groups to proteins is widespread in both endogenous metabolic processes, and and via environmental exposure, and results in enhanced adaptive immune responses by as yet uncharacterized mechanisms. The immune activation observed after protein oxidation is Th2-biased in nature, and we have linked this to allergy and hypersensitivity (4-6). This project will aim to elucidate the cellular and molecular mechanisms underlying aldehyde-induced activation, and will translate this knowledge to models of autoimmunity. This project will use techniques in molecula and cellular biology, protein biochemistry (in collaboration with the chemistry department), and in vitro and in vivo immunology.
1. Schiffner T, Pallesen J, Russell RA, Dodd J, de Val N, LaBranche CC, Montefiori D, Tomaras GD, Shen X, Harris SL, Moghaddam AE, Kalyuzhniy O, Sanders RW, McCoy LE, Moore JP, Ward AB, Sattentau QJ. 2018. Structural and immunological correlates of chemically stabilized HIV-1 envelope glycoproteins. Plos Pathog. 10: e1006986
2. Schiffner T, de Val N, Russell RA, de Taye SW, de la Pena AT, Ozorowski G, Kim HJ, Nieusma T, Brod F, Cupo A, Sanders RW, Moore JP, Ward AB, Sattentau QJ. 2015. Chemical cross-linking stabilizes native-like HIV-1 envelope glycoprotein trimer antigens. J. Virol. 90: 813
3. Schiffner T, Kong L, Duncan CJ, Back JW, Benschopp JJ, Shen X, Huang PS, Stewart-Jones GB, DeStefano J, Seaman MS, Tomaras GD, Montefiori DC, Schief WR, Sattentau QJ. 2013. Immunefocusing and enhanced neutralization induced by HIV-1 gp140 chemical cross-linking. J. Virol. 87: 10163-72
4. Moghaddam A, Olszewska W, Wang B, Tregoning JS, Helson R, Sattentau QJ, Openshaw PJ. 2006. A potential molecular mechanism for hypersensitivity caused by formalin-inactivated vaccines. Nature medicine 12:905-907.
5. Moghaddam AE, Gartlan KH, Kong L, Sattentau QJ. 2011. Reactive carbonyls are a major Th2-inducing damage-associated molecular pattern generated by oxidative stress. Journal of immunology 187:1626-1633.
6. Moghaddam AE, Hillson WR, Noti M, Gartlan KH, Johnson S, Thomas B, Artis D, Sattentau QJ. 2014. Dry roasting enhances peanut-induced allergic sensitization across mucosal and cutaneous routes in mice. The Journal of allergy and clinical immunology 134:1453-1456.