This project is in competition for funding from the NERC Great Western Four+ Doctoral Training Partnership (GW4+ DTP) for entry in October 2023. The GW4+ DTP consists of the Universities of Bath, Bristol and Exeter and Cardiff University plus five prestigious Research Organisation partners.
Lead Supervisor: Neil Brown & Hans Nuetzmann, University of Bath, Milner Centre for Evolution (MCE), Dept. Life Sciences
Co-Supervisor: Helen Fones & Ivana Guedlj, University of Exeter, Biosciences
Co-Supervisor: Martin Urban & Kim Hammond-Kosack, Rothamsted Research
Project Background: Fungal pathogens cause deadly human infections, destroy our crops, poison our food with harmful toxins, while also threatening wild-life and ecosystem health. Despite our best efforts, fungal pathogens cause the loss of ~10% of our crops, contaminate ~25% of food with toxins, decimate native tree populations, and cause human infections that have extremely high mortality rates. Worryingly, our ecosystems and society have become more vulnerable, as we witness a rise in fungal disease outbreaks and the evolution of more aggressive, antifungal-resistant, pathogens.
We rely on just a few classes of antifungal drugs to secure our safe food supply and to cure human infection. This has created a perfect storm for the evolution of antifungal resistance (AFR), as many of the major fungal pathogens of people and plants are present on our farms. Exposing pathogens to agricultural antifungals is believed to drive the evolution of cross-resistance to similar antifungals in hospitals, termed environmentally acquired resistance. Examples include Aspergilli and Fusaria which cause toxic cereal rots and life-threatening pulmonary, skin and eye infections, where antifungal resistance has been reported to contribute to poor treatment outcomes. But what is driving this increased threat of environmentally acquired resistance? Is it changes to our environment or altered agricultural practices? Where and when are these cross-over pathogens acquiring AFR on our farms? How do these adaptations impact on pathogen aggressiveness?
Our research will answer these important questions, helping us determine what environments and agricultural practices are driving the evolution of antifungal-resistant aggressive pathogens, and where and when these evolutionary reservoirs occur on our farms. This knowledge will support the development of improved farming practices to mitigate the risk of environmentally acquired resistance, protecting the shelf-life of our limited antifungal drugs, to the benefit of our crops, animals, ecosystems, and human health.
Project Aims and Methods: This PhD will adopt two work packages (WP) to understand what is driving the evolution of troublesome pathogens, and where this is occurring in our farming environments. WP1: We will use directed-evolution techniques to evolve Aspergillus and Fusarium species to environmental stresses which replicate climate change and agricultural intensification (i.e. temperature, humidity, salt, and pH stress) in the presence of differing levels of agricultural antifungals. Evolved and non-evolved strains will harbour constitutive GFP or RFP markers to facilitate comparative assays. Minimum inhibitory concentration (MIC) will be used to evaluate adaptations to different stresses along evolutionary time, and how this confers cross-resistance to clinical antifungals. Competition, fitness cost and plant pathology experiments will be used to model how these adaptations may influence fungal aggressiveness and population structure. We will use genomics and epigenetic (bisulfite) sequencing to identify genetic changes acquired through exposure to stress and antifungals, in multiple fungal lineages with phenotypic adaptations. Finally, CRISPR-Cas9 genome editing will be used to confirm these genetic adaptations confer phenotypic adaptations that enhance environmental stress tolerance and AFR evolution. WP2: We will sample distinct arable environments (crops, soils, residues) throughout annual farming cycles to create a collection of Aspergillus and Fusarium species. This will be used to monitor how pathogen abundance and AFR profiles change in response to altered practices and the environment. Sequencing and comparative genomics will be used to identify the genetic basis of adaptation in natural pathogens, which will be correlated with our lab-evolved strains. IMPACT: The knowledge generated in these WPs will enable us to determine which scenarios are driving the rise in troublesome pathogens on our farms. Does the use of irrigation in agriculture, which increases soil salinity, drive soil dwelling fungi to evolve stress tolerance mechanisms that promote AFR to both agricultural and clinical antifungals? Or, will future climates increase the rate at which AFR evolves? This knowledge will enable the design of better farming practices, to ensure the protection of crop, ecosystem, and human health.
Candidate requirements: Good knowledge/experience in microbiology and molecular biology, with a demonstrable interest in fungi and/or agricultural science. Bioinformatics skills would be advantageous.
Applicants must have, or be about to obtain, a UK Honours degree 1st or 2.1, or international equivalent.
Non-UK applicants must meet the programme’s English language requirement by 01/02/2023 (unless you will be awarded a UK degree or degree conducted in English before your PhD start).
Project partners: Our multidisciplinary collaboration between the Universities of Bath and Exeter with Rothamsted Research will exploit our strengths in evolutionary biology, plant pathology, bioinformatics, and mathematical modelling, utilising the state-of-the-art research facilities across the three institutions. The supervisors have an excellent record in delivering world-class science and supportive environments, where the student will benefit from undertaking research and training at each institution.
Training: Drs Brown & Nuetzmann (MCE, Bath) will provide training in evolutionary mycology and fungal genetics (CRSIPR-Cas9). Dr Fones & Prof Gudelj (Exeter) will support the identification of pathogens on the farm, and the modelling of evolved pathogen competitive fitness. Dr Urban & Prof Hammond-Kosack (Rothamsted) will support bioinformatics analyses and training to work in a CAT-3 plant pathology facility.
Enquiries and Applications:
Informal enquiries to Dr Neil Brown [Email Address Removed]
Formal applications via application form for PhD in Biology
Identify your application as for NERC GW4+ DTP competition in Section 3 Finance (question 2). Quote the project title and supervisor’s name in ‘Your research interests’.
More information about applying for a PhD at Bath may be found on our website.
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