HIV-1, Tuberculosis, Malaria and Hepatitis C Virus

Pathogen Co-infection: HIV-1, Tuberculosis, Malaria and hepatitis C virus

Supervisors: Professor Jane McKeating and Dr Peter Balfe.

Funder: EU FP7

Application deadline: 4th January 2013

PathCo will investigate the key role of pathogen evasion and dysregulation of host immune responses in co- infection associated morbidity.

This project will focus on in vitro and ex vivo co-infection model systems to study HCV-pathogen interactions, with the specific objectives of improving our understanding of pathogen co-infection effect(s) on host innate and adaptive immune responses. We will use new approaches to dissect pathogen interactions: ranging from the genesis of fluorescent labelled viruses to state- of-the-art tissue explant culture systems and novel humanized mouse models.

Studies of infected individuals will define pathogen-specific effects on host immune responses and consequences for disease progression.

Specific research projects include: 1. The role of HIV-1 infection and associated inflammation on HCV replication. 2. Identifying the common pathways defining Malaria and HCV liver tropism. 3. Generation of humanized mouse model systems supporting pathogen co-infection 4. The effect(s) of HIV-1 infection on HCV specific host immune responses.

PathCo brings together powerful multidisciplinary technologies that will improve our understanding of the complex interactions between infectious agents and the host immune response that will significantly improve the management of co-infection associated HCV disease.

The PhD place will be a 4 year appointment commencing October 2013 and is open to all EU nationals.

Enquiries to be directed to [email protected]

Applications to include a CV and covering letter/e-mail to [email protected]

References: Brimacombe, C., Grove, J., Meredith, L., Hu, K., Syder, A.J., Flores, M.F., Timpe, J., Krieger, S.E., Baumert, T.F., Tellinghuisen, T.L., Wong-Staal, F., Balfe, P., and McKeating, J.A. (2011). Neutralizing antibody resistant hepatitis C virus cell-to-cell transmission. J.Virol, 85: 596-605.

Syder, A.J., Lee, H., Baumert, T.F., Grove, J., McKeating, J.A., Macdonald, J., Chow, S., Chang, J., McKelvy, J., and Wong-Staal, F. (2011). Small molecule scavenger receptor B1 antagonists are potent HCV entry Inhibitors. J. Hepatology,54: 48-55.

Stamataki, Z., Shannon-Lowe, C., Shaw, J., Mutimer, D., Rickinson, A. B., Gordon, J., Adams, D. H., Balfe, P. & McKeating, J. A. (2009). Hepatitis C virus association with peripheral blood B lymphocytes potentiates viral infection of liver-derived hepatoma cells. Blood 113, 585-593.

Timpe, J. M., Stamataki, Z., Jennings, A., Hu, K., Farquhar, M. J., Harris, H. J., Schwarz, A., Desombere, I., Roels, G. L., Balfe, P. & McKeating, J. A. (2008). Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies. Hepatology 47, 17-24.