Pathogenic fungi are responsible for about 1.5 million deaths worldwide per annum and fungi also cause the spoilage of about 25% of the world’s crops. We wish to determine structures of selected GPCRs and other membrane proteins from pathogenic fungi to provide a platform for structure-guided drug design for the development of specific targeted anti-fungal reagents.

The project will start with the identification of potential target membrane proteins such as GPCRs that are involved in the pathogenicity of fungi, using both literature sources and the knowledge of collaborators involved in fungal research. Targets will be overexpressed and purified, with structures determined by single-particle cryo-EM and image processing. The successful candidate will be expected to become proficient in all steps of this process, and we already have extensive experience in the lab for all the steps. We have already developed methodology for using G proteins to stabilise the active state of a yeast GPCR (see references below) and there will also be the opportunity for generating nanobodies as required for the stabilisation of specific conformational states or complexes.

References

Velazhahan, V., Ma, N., Vaidehi, N., Tate, C.G. (2022)
Activation mechanism of the class D fungal GPCR dimer Ste2
Nature 603(7902): 743-748

Velazhahan, V., Ma, N., Pándy-Szekeres, G., Kooistra, A.J., Lee, Y., Gloriam, D.E., Vaidehi, N., Tate, C.G. (2021)
Structure of the class D GPCR Ste2 dimer coupled to two G proteins
Nature 589(7840): 148-153