Molecular basis of biological mechanisms. (360G-Wellcome-102572_Z_13_Z)

BK polyomavirus is the etiological agent in a number of diseases in the immunosuppressed such as: polyomavirus associated nephropathy in kidney transplant patients, haemorrhagic cystitis in bone marrow recipients and HIV-associated salivary gland disease. Despite this, there are currently no effective anti-viral agents targeting this virus. High-resolution structural information on the native virion and the conformational changes it undergoes during host cell infection are currently lacking. Using state of the art cryo-electron microscopy techniques I will achieve the following goals: 1) Determine the structure of native BKPyV capsid and packaged dsDNA genome 2) Characterise structural changes within the capsid of BKPyV during host cell infection 3) Determine the asymmetric structure of the minor capsid proteins VP2 and VP3 4) Use structure based drug design to identify inhibitors of cell entry and structurally characterise their mode of binding By successfully achieving these research objectives, we will gain significant insights into the various structural configurations adopted by this clinically relevant pathogen during host cell infection and in doing so create a platform for structure based drug design of novel antivirals.