This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP).
The SWBio DTP is funded by BBSRC and involves a partnership of world-renown universities, research institutes and industry across the South West and Wales. This partnership represents a distinctive group of bioscientists with established international, national and regional networks and widely recognised research excellence. We aim to provide students with outstanding interdisciplinary research training.
Studentships are available for entry in October 2023.
All SWBio DTP projects will follow a structured 4-year PhD programme, combining traditional project-focussed studies with a taught first year which includes directed rotation projects.
Supervisory Team:
Lead supervisor: Dr Javier Gonzalez, University of Bath, Department of Health (email: [Email Address Removed])
Co-supervisors: Prof Gavin Welsh (University of Bristol), Dr Francoise Koumanov (University of Bath) and Dr Emma Vincent (University of Bristol)
The Project:
Red blood cell production (erythropoiesis) is a fundamental process in human health. Red blood cells are required for oxygen transport, which in turn affects physical function during daily activities. The key regulatory hormone which mediates erythropoiesis is erythropoietin (EPO), secreted mainly by the kidney. The most well-known process which stimulates EPO production is oxygen sensing. However, preliminary data suggest that specific metabolites may also stimulate EPO production. If this is the case, this could provide a new strategy to maintain health and physical function with nutritional and/or pharmacological strategies.
The aim of this project is to understand the effect and mechanisms by which key metabolites regulate EPO secretion. To achieve this, the successful student will be provided training in techniques for studying human physiology and metabolism in vivo, cell and organoid culture, and large-scale population cohort data. This will address the aim of the project with triangulation of key techniques and provide the student with a sought-after interdisciplinary skill set to platform to a future scientific career. Specific techniques will include, human indirect calorimetry, nutritional profiling and intervention, exercise testing, blood sampling and biochemistry and measures of red blood cell mass. The student will also become proficient in tissue culture, learning to maintain human kidney cells and organoids and using these to investigate the mechanism underlying EPO production upon betahydroxybutyrate stimulation. This will include exploring the changes in intracellular metabolism in response to betahydroxybutyrate using stable isotope labelling techniques coupled to mass spectrometry. This technique will allow the student to measure intracellular metabolism and pathway flux in real-time, tracking how the metabolic pathways of the cell respond to ketone stimulation. The student will also learn to carry out genetic analyses using large publicly available datasets and the well characterised NURTuRE cohort of CKD patients, which includes whole genome sequencing of the cohort and deep clinical phenotyping. The student will use an applied technique in genetic epidemiology called Mendelian randomization to investigate whether there is a causal relationship between ketones and EPO production.
In summary, this project will provide the student with the means to tackle a research question from multiple angles and upon completion of the PhD leave them with a highly desirable skill set.
Project keywords: human physiology, cell signalling, metabolism, renal physiology.
Requirements:
Applicants should 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 appropriate area of science or technology. Applicants with a Lower Second Class degree will be considered if they also have Masters degree or have significant relevant non-academic experience.
In addition, due to the strong mathematical component of the taught course in the first year and the quantitative emphasis in our projects, a minimum of a grade B in A-level Maths or an equivalent qualification/experience* is required.
* Physics A-level (grade B and above) or units in your degree with a significant mathematical component, e.g. maths, statistics, bioinformatics.
Applicants must ensure they highlight their Maths background within their application and to upload any supporting evidence.
If English is not your first language, you will need to have achieved Academic IELTS 7.0 overall (with no less than 6.5 in any of the four skills). Find details of other acceptable tests and further information on our website.
Enquiries and Applications:
Informal enquiries are welcomed and should be directed to the lead supervisor.
Formal applications should be submitted on the University of Bath’s online application form for a PhD in Biosciences (Biology & Biochemistry). Note: if you are successful, you will be transferred to the PhD in Health (SWBio DTP) programme when we issue an offer of study.
When completing the form, please identify your application as being for the SWBio DTP studentship competition in Section 3 Finance (question 2) and quote the project title and lead supervisor’s name in the ‘Your research interests’ section. You may apply for more than one project within the same application but you should upload a separate (clearly labelled) personal statement for each one, outlining your interest and suitability for that particular project.
See our website for more information about applying for a PhD at Bath.
Equality, Diversity and Inclusion:
We want to support diverse and inclusive work environments. We therefore welcome applications from individuals regardless of their race, ethnicity, sexual orientation, religion, age, gender or disability status.
If you have circumstances that you feel we should be aware of that have affected your educational attainment, then please feel free to tell us about it in your application form. The best way to do this is a short paragraph at the end of your personal statement.
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