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Discovery of novel antibiotic natural products from spider fungi (GANESANA_U23SF)


   School of Pharmacy


About the Project

Antimicrobial resistance is a major healthcare challenge globally. Our approach to solving this global crisis is to hunt for novel natural products from microorganisms as leads for drug discovery. We have the largest European collection of the rare Gibellula fungus, which in the wild grows exclusively by colonizing spiders, killing them, and using the cadavers as hosts. In this project, you will culture Gibellula strains in the laboratory and isolate and purify biologically active natural products from the fungi. We will employ two strategies in parallel: a) Fermentation under varying conditions and addition of small molecule elicitors to induce biosynthetic gene clusters, and b) Whole genome sequencing and expression of biosynthetic gene clusters in heterologous hosts. From these experiments, extracts will be prepared and subjected to bioassay-guided separation with antibacterial, antifungal and antiparasitic assays. Components of interest will be purified, their structures elucidated, and biological activities profiled in detail. The project will provide knowledge and training in the latest methods in natural products chemistry, microbiology, genomics, and antibiotic discovery.


Funding Notes

This PhD project is offered on a self-funding basis. It is open to applicants with funding or those applying to funding sources. Details of tuition fees can be found at View Website
A bench fee is also payable on top of the tuition fee to cover specialist equipment or laboratory costs required for the research. Applicants should contact the primary supervisor for further information about the fee associated with the project.

References

i) Aldholmi, Mohammed et al. “Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis.” Angewandte Chemie (International ed. in English) vol. 61,23 (2022): e202203175. doi:10.1002/anie.202203175
ii) Aldholmi, Mohammed et al. “Epigenetic modulation of secondary metabolite profiles in Aspergillus calidoustus and Aspergillus westerdijkiae through histone deacetylase (HDAC) inhibition by vorinostat.” The Journal of antibiotics vol. 73,6 (2020): 410-413. doi:10.1038/s41429-020-0286-5

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