Opportunities to join the lab.
Funded by the Wellcome Trust
The Hardwick lab was recently awarded an 8 year grant to study mechanisms of cell division and aneuploidy in Cryptococcus.
Please contact kevin.hardwick@ed.ac.uk with your CV if you are interested in post-doctoral or graduate RA positions.
PhD studentships
Structure-driven dissection of kinases and phosphatases in the fungal pathogen Cryptococcus neoformans
Cryptococcus neoformans is an understudied fungal pathogen with an unusual life cycle, forming polyploid Titan cells during infection in a bid to evade the immune system. It kills hundreds of thousands of immune-compromised AIDS patients each year, mainly in Africa. Mps1 and Bub1 are central players in the mitotic spindle checkpoint and strong, candidate drug targets. You will express, purify, crystallise and solve the structures of the highly conserved kinase domains of CnBub1, CnMps1 and other kinases and PPases. Their structures will be used to screen for and identify small molecule inhibitors. CRISPR-mediated genome engineering will be employed to determine the consequences of specific point mutations in conserved motifs/domains. How do they impact viability, polyploidy, Titan cell formation and infectivity? Small molecule inhibitors will be screened for that produce similar loss of function phenotypes. Longer term these inhibitors should prove useful in combination therapy treatments, alongside anti-microtubule drugs.
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