PhD Studentship : Engineering Biology: Fully Funded PhD Studentship in Unlocking Fungal Biosynthetic Potential to Combat Antimicrobial Resistance

Antimicrobial resistance (AMR) is one of the most pressing global threats to human health, agriculture, and food security. The misuse and overuse of antibiotics have accelerated the natural evolutionary process of resistance, rendering many existing treatments ineffective. To combat this crisis, there is an urgent need to discover new bioactive compounds, particularly antibiotics, many of which originate from fungi, bacteria, and plants as secondary metabolites (SMs). These natural products provide ecological advantages to the organisms that produce them and often possess potent antimicrobial properties. Fungi are a rich source of such compounds, with notable examples including penicillin, lovastatin, and ciclosporin. Advances in genome sequencing and bioinformatics have revealed that fungal genomes contain numerous biosynthetic gene clusters (BGCs) capable of producing novel SMs. However, many of these clusters remain silent under standard laboratory conditions. Techniques such as heterologous expression, where gene clusters are transferred to a host strain like Aspergillus oryzae NSAR1, have proven effective in activating these cryptic pathways. A promising but understudied fungal candidate is Escovopsis weberi, isolated from the leaf-cutter ant ecosystem. This filamentous fungus thrives in a highly competitive microbial environment and produces SMs with antifungal and antibacterial properties. Genomic analysis suggests that E. weberi harbours many unexplored BGCs. However, the lack of genetic tools and detailed chemical profiling has hindered progress.

This multidisciplinary research project aims to address AMR by developing tools to unlock the biosynthetic potential of E. weberi. Using microbiological, chemical, and genetic techniques, different biosynthetic gene clusters will be expressed in the host organisms to produce novel compounds. Fungal extracts will be analysed using liquid chromatography-mass spectrometry (LC-MS/MS), and promising compounds will undergo purification, structural elucidation via MS and NMR, and antimicrobial screening. Biosynthetic pathways consist of several protein domains, encoded in both linear and non-linear manners, to form an assembly line that produces the natural product of interest. Biosynthetic pathways that produce promising compounds will therefore be interrogated via protein studies to probe their biomolecular assembly to fully understand these biosynthetic pathways. Students will gain hands-on experience in microbial fermentation, genetic engineering, natural product chemistry, bioinformatics, protein purification and conducting protein assays.

The project will be conducted in collaboration between Swansea University’s Department of Biosciences and the University of Bristol’s School of Chemistry. This is an excellent opportunity for students interested in microbiology, biotechnology, chemical biology, and drug discovery to engage in cutting-edge research addressing a major global health challenge.

Our aim as the SWBio DTP is to support students from a range of backgrounds and circumstances. Where needed, we will work with you to take into consideration reasonable project adaptations (for example to support caring responsibilities, disabilities, other significant personal circumstances) as well as flexible working and part-time study requests, to enable greater access to a PhD.  All our supervisors support us with this aim, so please feel comfortable in discussing further with the listed PhD project supervisor to see what is feasible.

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