Biological Sciences: Fully Funded EPSRC and Swansea University PhD Scholarship: Unearthing fungal chemodiversity (RS271) Closing date: 11 January 2023
Key Information
Funding providers: Engineering and Physical Sciences Research Council (EPSRC) DTP and Swansea University’s Faculty of Science and Engineering. Subject areas: Biological chemistry, Microbiology, natural products
Project start date:
- 1 October 2023 (Enrolment open from mid-September)
Project supervisors:
- Dr Claudio Greco
- Professor Dan Eastwood
Aligned programme of study: PhD in Biological Sciences
Mode of study: Full-time
Project description:
One of the biggest threats to global health and food security of our time is antibiotic resistance (AMR) causing existing antibiotics to become ineffective as a treatment for humans and livestock. In order to tackle the AMR crisis, new antibiotics need to be discovered and a large proportion of antibiotics originate from fungi, bacteria and plants as natural products. These, also called secondary metabolites, are produced by organisms as they provide an ecological and physical advantage to better survive in their habitat. Filamentous fungi are a long-time source of bioactive compounds used by agrochemical, food, and pharmaceutical industries.
Bioinformatic analyses of fungal genomes have revealed that fungi contain a large number of gene clusters which appear to encode pathways for secondary metabolites, yet their chemical products are unknown making them inaccessible for drug discovery studies. Improvement in our understanding of how this gene clusters are regulated and functional analysis using heterologous expression systems could lead to the discovery of new natural products, and these may include new classes of antibiotic.
The overarching aim of this study is to investigate novel bioactive molecules and the biosynthetic gene clusters that regulate their production in several different fungi. In this multidisciplinary project, microbiological, bioinformatic and chemical techniques will be used to discover new natural products and investigate their biological and ecological activities. The project has three main objectives.
OBJECTIVE 1. Optimise the heterologous host A. oryzae NSAR1 for the expression of several unique biosynthetic gene clusters (BGCs) identified. A. oryzae NSAR1 is already used widely as a heterologous expression strain. Any new metabolite will be characterised using a range of analytical techniques and screened for bioactivities.
OBJECTIVE 2. Bioinformatics and metabolomics analysis of two newly isolated fungal species will enable the identification of bioactive metabolites. Chemical analysis will characterise the structure of new compounds.
OBJECTIVE 3. Development endogenous transformation and functional analysis will investigate the link between the new compounds to their BGCs. This method will be used to investigate the biosynthesis of these compounds and will be used to generate new derivatives for bioactivity studies.
Techniques that will be undertaken during the project:
- Microorganism fermentation
- Genetic manipulation
- Natural product purification through preparative HPLC
- LC-MS/MS for metabolite profiling and dereplication
- Structural elucidation with MS and NMR techniques
- Antimicrobial activity assays, including MIC determination
- Bioinformatics
References
- Greco et al. (2019) Curr. Opin. Microbiol. 51:22
- Williams et. al.(2016) Angew. Chem. Int. Ed. 55:6784
- Greco et al. (2019) Chem. Sci. 10:2930
Eligibility
Candidates must normally hold an undergraduate degree at 1st or 2.1 level in Chemistry, Biology, Biotechnology or a related subject, or a master’s degree with a minimum overall grade at ‘Merit’ (or Non-UK equivalent as defined by Swansea University), and have some experience relevant to the project.
English Language requirements: If applicable – IELTS 6.5 overall (with at least 6.0 in each individual component) or Swansea recognised equivalent. This scholarship is open to candidates of any nationality.
NB: If you are holding a non-UK degree, please see Swansea University degree comparisons to find out if you meet the eligibility. If you have any questions regarding your academic or fee eligibility based on the above, please email pgrscholarships@swansea.ac.uk with the web-link to the scholarship(s) you are interested in.
Funding
This scholarship covers the full cost of tuition fees and an annual stipend at UKRI rate (currently £17,668 for 2022/23).
Additional research expenses will also be available.
How to Apply
To apply, please complete your application online with the following information:
- Course choice – please select Biological Sciences / PhD / Full-time / 3 Year / October In the event you have already applied for the above programme previously, the application system may issue a warning notice and prevent application, in this event, please email pgrscholarships@swansea.ac.uk where staff will be happy to assist you in submitting your application.
- Start year – please select 2023
- Funding (page 8) –
- ‘Are you funding your studies yourself?’ – please select No
- ‘Name of Individual or organisation providing funds for study’ – please enter ‘RS271 – PhD BioSci’
*It is the responsibility of the applicant to list the above information accurately when applying, please note that applications received without the above information listed will not be considered for the scholarship award.
One application is required per individual Swansea University led research scholarship award; applications cannot be considered listing multiple Swansea University led research scholarship awards.
We encourage you to complete the following to support our commitment to providing an environment free of discrimination and celebrating diversity at Swansea University:
- Equality, Diversity and Inclusion (EDI) Monitoring Form (online form)
As part of your online application, you MUST upload the following documents (please do not send these via email):
- CV
- Degree certificates and transcripts (if you are currently studying for a degree, screenshots of your grades to date are sufficient)
- A cover letter including a ‘Supplementary Personal Statement’ to explain why the position particularly matches your skills and experience and how you choose to develop the project.
- Two references (academic or previous employer) on headed paper or using the Swansea University reference form. Please note that we are not able to accept references received citing private email accounts, e.g. Hotmail. Referees should cite their employment email address for verification of reference.
- Evidence of meeting English Language requirement (if applicable).
- Copy of UK resident visa (if applicable)
Informal enquiries are welcome, please contact Dr Claudio Greco (Claudio.greco@swansea.ac.uk).
*External Partner Application Data Sharing – Please note that as part of the scholarship application selection process, application data sharing may occur with external partners outside of the University, when joint/co- funding of a scholarship project is applicable.