The project combines molecular biology and neuroscience to investigate the role of neural stem cells and new neurons in regulation of body weight. To study changes in neural networks, cell dynamics and proliferation, you will learn the cutting-edge technologies, including patch-seq (a combination of patch-clamp electrophysiology and single-cell RNA sequencing, scRNAseq), calcium imaging, and live cell imaging.
Obesity remains one of the biggest medical and socioeconomic challenges. It increases the risk of depression and cancer and it is the second leading cause of disability. In the UK, 64% of adults and 22% of children are overweight or obese. 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. There is a clinical need for new safer neuro-active anti-obesity medications.
We have developed a lipidized analogue of the neuropeptide Prolactin Releasing Peptide, called LiPrRP. It reduces weight gain in a mouse model of diet-induced obesity (DIO), it accumulates in the brain, and stimulates appetite-controlling neurons in the hypothalamus. In addition, LiPrRP increases survival of new hypothalamic neurons generated from the resident neural stem cells in the process of adult neurogenesis. LiPrRP is scheduled for clinical trials in 2021-22. However, cellular, and molecular mechanisms of action of LiPrRP need to be fully understood.
Our lab has expertise in neuroscience, physiology, stem cell biology and obesity research. In this project you will receive training in advanced molecular and cellular techniques. You will determine how LiPrRP influences physiology and gene expression of hypothalamic neurons, glia, and stem cells. To obtain multi-dimensional data on individual cells, you will utilize the cutting-edge patch-seq method. This powerful technology allows recording of a cell before its cellular content is collected for subsequent analysis. This data will help determine how LiPrRP affects function and gene expression of individual cells. Finally, you will use time-lapse imaging of neural stem cells to elucidate how LiPrRP influences cell dynamics, self-renewal, and cell proliferation.
You will benefit from excellent research support including the Genomic Research Hub and Medicines Discovery Institute. In addition, we collaborate 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. These collaborations expand the technical possibilities of our lab and offer a possibility for overseas scientific stays.
*Please note this project can be completed as an MPhil or a PhD*
A 1st or Upper 2nd class UK honours degree or equivalent. Please visit School of Biosciences Postgraduate Research for more details.
For those whose first language is not English, IELTS with an overall score of 6.5 with 5.5 in all subskills, or equivalent. Please see our English Language Requirements guidance for more details.
How to Apply
To submit a formal application via Cardiff University’s online application service, click the 'Institution Website' button on this advert; in the ‘Apply’ box at the top-right of the page, select Qualification (Doctor of Philosophy/Master of Philosophy), Mode of Study (Full Time) and Start Date (this can be flexible as it is a self-funded project). This will take you to the application portal.
Candidates must submit the following:
• Supporting statement
• Qualification certificates
• Proof of English language (if applicable)
In the research proposal section of the application, specify the project title and supervisors of the project. In the funding section, specify that you will be self-funding. If you are applying for more than one Cardiff University project with the same entry intake, please note this in the research proposal section as the form only allows you to enter one title.