membrane proteins which are potential antifungal drug targetsCollege of Health & Life Sciences - Studentships Location: Aston University Main Campus
Basis: Full Time Closing Date: 23.59 hours BST on Sunday 30 April 2023 Reference: R230066 Release Date: Tuesday 07 March 2023
Department: College of Health and Life Sciences
Contract Type: Fixed Term
Basis: Full Time
Closing Date: 30th April 2023
Supervisor: Dr Alice Rothnie
Project Reference: HLSMIBTPMembraneProteins
Key words: Antifungal, membrane protein, SMALP
Applications are invited for a four-year Postgraduate studentship, as part of the MIBTP programme, to be undertaken within the Biosciences Research Group at Aston University. The successful applicant will join an established experimental group working on expression, purification and characterization of membrane proteins which are novel antifungal drug targets. The studentship is offered in collaboration with the company F2G Ltd.
The position is available to start in October 2023.
This studentship includes a fee bursary to cover the home/EU fees rate, plus a maintenance allowance of £16,062 in 2022/3.
Overseas applicants may apply for this studentship but will need to pay the difference between the ‘Home' and the ‘Overseas' tuition fees. Currently the difference between ‘Home' and the ‘Overseas' tuition fees is £10,504 in 2022/3. As part of the application, you will be required to confirm that you have applied for, or, secured this additional funding.
Background to the Project
An estimated 1.5 million people die from invasive fungal infections (IFI) each year. As well as the increasing patient population (currently exacerbated by the influence of COVID-associated IFIs), the problem of increasing resistance to current therapies is worrying. The spread of antifungal resistance has been identified by the WHO and CDC as a serious threat to health. With limited treatment options there is an urgent need for new antifungal drugs acting via novel mechanisms of action. F2G Ltd have several antifungal programmes at different stages that are each believed to target membrane proteins. The phase 3 antifungal compound olorofim acts by inhibiting the mitochondrial membrane protein dihydroorotate dehydrogenase (DHODH). Additionally, a multi-spanning membrane protein has been identified as the target of a preclinical series of antifungals, and a third potential membrane protein target has been found, that requires active protein to progress
Traditionally, membrane proteins have been difficult to work with so that preparation of recombinant versions of potential drug targets for inhibitor screening has not always been possible. However, this collaboration will combine Aston's expertise in membrane protein expression, particularly in yeast, and the use of innovative solubilisation techniques such as SMA lipid particles (SMALPs) to enable these membrane proteins to be purified in their native form, allowing their activity to be studied. The proposed target proteins will be expressed and purified, followed by the development of methods to study the interaction between the transmembrane protein and potential drugs at the molecular level. Assay development of novel membrane protein targets will allow screening for inhibitors that will drive the identification of starting points for the discovery of new drugs.
Oliver JD, Sibley GEM, Beckmann N, Dobb KS, Slater MJ, McEntee L, du Pré S, Livermore J, Bromley MJ, Wiederhold NP, Hope WW, Kennedy AJ, Law D, Birch M.(2016) F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase. Proc Natl Acad Sci U S A. 113(45):12809-12814. doi: 10.1073/pnas.1608304113.
Unger L, Ronco-Campaña A, Kitchen P, Bill RM & Rothnie AJ (2021) Biological Insights from SMA-extracted proteins. Biochem. Soc. Trans 49(3):1349-1359 doi: 10.1042/BST20201067
Ayub H, Clare M, Milic I, Chmel NP, Böning H, Devitt A, Krey T, Bill RM & Rothnie AJ (2020) CD81 extracted in SMALP nanodiscs comprises two distinct protein populations within a lipid environment enriched with negatively charged headgroups. BBA Biomembranes 1862; 183419
The successful applicant should have been awarded, or expect to achieve, a Masters degree in a relevant subject with a 60% or higher weighted average, and/or a First or Upper Second Class Honours degree (or an equivalent qualification from an overseas institution) in Biochemistry, Biological Sciences or related subject. Preferred skill requirements include knowledge/experience of membrane protein expression and purification.
For formal enquiries about this project contact Dr Alice Rothnie by email at [email protected]
Submitting an application
As part of the application, you will need to supply:
Details of how to submit your application, and the necessary supporting documents can be found here.
Please select “Research Biomedical Sciences” from the application form options.
The application must be accompanied by a “research proposal” statement. An original proposal is not required as the initial scope of the project has been defined, candidates should take this opportunity to detail how their knowledge and experience will benefit the project and should also be accompanied by a brief review of relevant research literature.
Please include the supervisor's name, project title and project reference in your Personal Statement.
If you require further information about the application process please contact the Postgraduate Admissions team at [email protected]