This 3.5 year studentship is part of research within the Healthy Lifespan Institute (HELSI) at The University of Sheffield. HELSI is dedicated to the understanding and prevention of multimorbidity (the presence of two or more chronic health conditions that create disability and reduce quality of life). We are taking a unique multidisciplinary approach that spans biological and social sciences to create new practices, policies and products that target multiple conditions and help people live longer, healthier and more independent lives.
Students within the Healthy Lifespan Institute are valued and active members of the Institute and vital in contributing to our aims and helping to effect real change. You will be part of a wider multidisciplinary network of PhD students (see here) and will have the chance to influence and lead Institute activity, seminars and events, and meeting leaders in the field.
Chronic organ dysfunction is the most common cause of morbidity among aging individuals. This process can be simply characterised as the organ not performing its expected function. Generally, the process of organ dysfunction begins slowly, but it is often progressive leading to organ failure where normal homeostasis cannot be maintained without clinical intervention. Chronic organ dysfunction puts stress on other systems often causing a cascade effect (e.g. disorders of the heart stress the lungs and kidneys). A key feature of organ dysfunction is the loss of organ fluid haemostasis, where normally, vascular/lymphatic endothelial cells play key roles in the maintenance of vascular/organ homeostasis by regulation of vessel permeability. A key regulatory of this endothelial barrier function is the hormone adrenomedullin (AM).
AM is a multifunctional peptide that is secreted from a large range of organs/tissues, including endothelial cells of both the vascular and lymphatic systems. It plays a key role in maintenance of fluid balance and so proper organ function. AM dysregulation has been shown to be associated with multiple organ dysfunctions such as congestive heart failure, chronic kidney disease and many more. Mice lacking AM and some of its receptors display deleterious changes in the both vascular and lymphatic endothelial cells and severe organ fibrosis with marked oxidative stress and accelerated vascular senescence. Other genetic changes appear to confer improvements in ageing processes in mice.
AM mediates its function through two distinct receptors known as the AM1R and AM2R. The specific roles of these receptors in aging and particularly aging of endothelial cells is not well-understood, so its role in organ dysfunction is also yet to be resolved. Our group has developed agents which can selectively modulated these two receptors. These tools provide a unique opportunity to dissect the AM signalling system in the context of endothelial cell aging. Using these tools, we will test the hypothesis:
AM signalling through its two receptors alters with age in vascular and lymphatic endothelial cells
To test this hypothesis, the student will become proficient in primary cell culture, using immunohistochemistry, qPCR and cell-based assays to determine changes in AM1 and AM2 receptor functions with cell age. The student will also work closely with colleges within the department of chemistry to assess novel tools to target the AM signalling system.
The student will be based primarily in the Department of Oncology and Metabolism and supervised by Dr Gareth Richards and co-supervised by Prof Ilaria Bellantuono, Prof Tim Skerry and Prof Joe Harrity from the Department of Chemistry. All of the supervisors are experts in their field, and have a track record of supervising PhD students successfully and publishing data from PhD student projects in good journals. Former graduates have gone on to careers in science in academic and industrial research and teaching in the UK and abroad.
Candidates must have:
● Upper second class honours degree (2.1) or above in biological science, and ideally some demonstrable laboratory based experience in the area of cell biology.
● Candidates will be expected to provide a convincing justification as to why they would like to undertake the project in their application statement, demonstrating any research knowledge and, if applicable, any experience relevant to the project.
● Candidates should be home based students to qualify for full support. (Overseas students are eligible but must be able to top up the tuition fee requirement for international students)
Complete a Postgraduate Research application form here. Please state the title of the studentship, the main supervisor and select Department of Infection, Immunity & Cardiovascular Disease as the department.
If you have any queries, please contact Gareth Richards, Department: Oncology and Metabolism, Faculty: FMDH, E-mail: [Email Address Removed]