This project is one of a number that are in competition for funding from the ‘GW4 BioMed MRC Doctoral Training Partnership’ which is offering up to 18 studentships for entry in September 2020.
The DTP brings together the Universities of Bath, Bristol, Cardiff and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities.
Lead supervisor: Dr Neil Brown, Department of Biology & Biochemistry, University of Bath
Co-supervisors: Prof Jean van den Elsen (Bath), Prof Karen Edler (Bath) and Prof Christiane Berger-Schaffitzel (Bristol)
Fungi threaten our health, killing thousands every year. New ways to stop the spread of fungal pathogens must be found.
Fungal receptors are targets for disease control, due to their fungal-specificity, exposed cell-surface location and importance in coordinating fungal biology. But we do not know how these vital receptors bind their ligands to regulate their dynamic structures and interactions with membrane lipids and proteins, controlling cell signalling. These deficiencies impede the development of receptor-targeting drugs. How will we address these shortcomings? Initially we will focus on fungal receptors that regulate sex in the human pathogen and harmful toxin-producer, Aspergillus nidulans. Fungal sex is central to disease, providing a means of dispersal, stress survival and genetic variation that contributes to the rise in drug resistance.
We aim to develop a cutting-edge nanotechnology to study fungal receptors in their native membrane environment. Fungal receptors will be excised from the membrane in styrene maleic acid lipid nanoparticles, preserving their native membrane complexes. This will be used in combination with a new native gel electrophoresis separation system (SMA-PAGE), mass spectrometry, immunoblotting, crystallography and Cryo-EM to 1) measure protein quaternary structure, 2) identify novel receptor interactions with ligands, proteins and lipids, and 3) yield intact receptor complexes for biophysical or structural studies. This will deliver the first insights into how dynamic receptor structures and their complex lipid-protein interactions regulate function. CRISPR-Cas9 fungal gene editing will be used to disrupt receptor-interactions, demonstrating their importance to receptor function.
Collectively, this multidisciplinary project will provide the students with excellent training in advanced chemical nanotechnology, structural biology, fungal molecular genetics and gene editing.
The translational impact of this research will deliver a platform to develop novel antifungal drugs to impede the rise and spread of fungicide-resistant pathogens.
Applicants for a studentship must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an area appropriate to the skills requirements of the project.
IMPORTANT: In order to apply for this project, you should apply using the DTP’s online application form: https://cardiff.onlinesurveys.ac.uk/gw4-biomed-mrc-doctoral-training-partnership-student-appl
You do NOT need to apply to the University of Bath at this stage – only those applicants who are successful in obtaining an offer of funding form the DTP will be required to submit an application to study at Bath.
More information on the application process may be found here: https://www.gw4biomed.ac.uk/doctoral-students/
APPLICATIONS CLOSE AT 17:00 ON 25 NOVEMBER 2019.