InstructApplications are invited for a 3-year PhD fellowship to join the laboratory of Carlo Petosa at the Institute for Structural Biology (IBS) in Grenoble, France in the autumn of 2019.
Invasive fungal infections are a major global health concern, causing over a million deaths per year. Because of the limited number of antifungal drugs and the emergence of drug-resistant strains there is an urgent need to develop new therapeutic strategies. We recently identified an epigenetic reader domain, the bromodomain from the fungal transcription factor Bdf1, as a potential new target for antifungal therapy (Mietton et al., 2017), opening up exciting new possibilities for developing epigenetic drugs to combat fungal infection. More recently, we identified another epigenetic player, the RSC complex, as a potentially superior antifungal target. The RSC complex is a 16-subunit, 1 MDa assembly that mediates chromatin-related processes by sliding or ejecting nucleosomes. Several RSC subunits are essential for viability or proper fungal growth and contain druggable ligand-binding pockets, including six bromodomains.
Our long-term goal is to structurally and functionally characterize the RSC complex in Candida albicans, a major human fungal pathogen, and to identify small-molecule inhibitors for translational development into an antifungal drug. Towards this end, the present project aims to characterize the C. albicans RSC complex in terms of subunit composition and biochemical activity and determine its 3D structure using cryo-electron microscopy and crystallography. The project is a collaboration of four partner labs with complementary expertise in fungal genetics and epigenetics, proteomics, biochemistry and structural biology.
For more information and to apply, click here.
