We will combine molecular biology and neuroscience to investigate the role of neural stem cells and new neurons in regulation of body weight and anti-obesity therapeutics. You will learn the cutting-edge technologies, including patch-seq (a combination of patch-clamp electrophysiology and single-cell RNA sequencing, scRNAseq), multielectrode array recording, calcium imaging, and live cell imaging. Obesity remains one of the biggest medical and socioeconomic challenges. It increases the risk of depression (1) and cancer (2) and it is the second leading cause of disability (3). Treatment of obesity should involve anti-obesity drugs; unfortunately, several anti-obesity drugs originally approved for clinical use were later rejected for severe side effects (4-6). There is a clinical need for new safer neuro-active antiobesity medications. We have developed a lipidized analogue of the neuropeptide Prolactin Releasing Peptide (PrRP), called LiPR. It reduces weight gain in a mouse model of diet-induced obesity (DIO) (7, 8) by stimulating appetite-controlling neurons in the hypothalamus (9). In addition, LiPR increases survival of new hypothalamic neurons generated from the resident neural stem cells in the process of adult neurogenesis. LiPR is scheduled for clinical trials in 2022-23. However, its mechanisms of action of LiPR need to be fully understood. The key research question is what genes and physiological processes are downstream of LiPR in hypothalamic cells. In this project you will receive training in advanced molecular and cellular techniques to address following objectives.
You will determine how LiPR influences physiology and gene expression of hypothalamic neurons, glia, and stem cells. Using multi-electrode arrays and calcium imaging, you will determine how LiPR affects excitability of hypothalamic neuronal networks. To obtain multi-dimensional data on individual cells, you will utilize the cutting-edge patch-seq method (10, 11). This powerful technology allows recording of a cell before its cellular content is collected for subsequent analysis. This will determine how LiPR affects function and gene expression of individual cells. Finally, you will use time-lapse imaging of neural stem cells to elucidate how LiPR influences cell dynamics. The supervisory team has shared and complementary expertise in neuroscience and obesity research, notably PrRP (12) making us ideal mentors for this project.
We will combine our expertise in physiology and stem cell biology (13) (Petrik Lab, Cardiff), glia and metabolism (14, 15) (Ellacott Lab, Exeter) and bioinformatics (16)(Zhou Lab, Cardiff) to complement the research plan. Your interests and preliminary data will allow you to steer the project in specific directions. For example, you can emphasize RNAseq over screening of neuronal networks. Or, if you are more interested in physiology, the calcium imaging and electrophysiology can be emphasized over RNAseq.
You will benefit from excellent research support including the Genomic Research Hub and Medicines Discovery Institute (Cardiff) and the Center for Excellence in Diabetes Research (Exeter). In addition, we collaborate with Webber Lab (UK Dementia Research Institute, Cardiff) on omics approaches and bioinformatics, with Maletinska Lab (Institute of Organic Chemistry and Biochemistry, Czech Republic) on protein modifications and biochemistry, and with Sierra and Encinas Labs (Achucarro Basque Center for Neuroscience, Spain) on inflammation, microglia, and stem cell biology.
Applications open on 2nd September 2022 and close at 5.00pm on 2nd November 2022.
About the GW4 BioMed2 Doctoral Training Partnership
The partnership brings together the Universities of Bath, Bristol, Cardiff (lead) 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, with opportunities to participate in interdisciplinary and 'team science'. The DTP already has over 90 studentships over 6 cohorts in its first phase., along with 20 students in its second phase.
Residency: The GW4 BioMed2 MRC DTP studentships are available to UK and International applicants. Following Brexit, the UKRI now classifies EU students as international unless they have rights under the EU Settlement Scheme. The GW4 partners have all agreed to cover the difference in costs between home and international tuition fees. This means that international candidates will not be expected to cover this cost and will be fully funded but need to be aware that they will be required to cover the cost of their student visa, healthcare surcharge and other costs of moving to the UK to do a PhD. All studentships will be competitively awarded and there is a limit to the number of International students that we can accept into our programme (up to 30% cap across our partners per annum).
Academic criteria: Applicants for a studentship must have obtained, or be about to obtain, a UK degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.
English requirements: If English is not your first language you will need to meet the English language requirements of the university that will host your PhD by the start of the programme. Please refer to the relevant university for further information.
How to Apply
A list of all the projects and how to apply is available on our website at gw4biomed.ac.uk. You may apply for up to 2 projects.
Please complete an application to the GW4 BioMed2 MRC DTP for an ‘offer of funding’. You may also need to make an application for an 'offer to study' to your chosen institution(s) – further details are on the website.
Please complete the online application form by 5.00pm on Wednesday, 2nd November 2022. If you are shortlisted for interview, you will be notified by Friday 16th December 2022. Interviews will be held virtually on 25th and 26th January 2023.
For informal enquiries, please contact [Email Address Removed]
For project related queries, please contact the respective supervisors listed on the projects.