Understanding the role of glucose variability in platelet hyperactivity in subject with type 2 diabetes.
Project Details:
Increased cardiovascular disease is the foremost reason of death in patients with type 2 diabetes. Obesity and diabetes are associated with insulin resistance (IR) and a hypercoagulable state, both of which play a role in the pathogenesis of atherothrombosis. Blood platelets play a privotal role in the atherthrombotic process by upholding and promoting vascular inflammation and thrombotic occlusion of key blood vessels. The mechanism linking IR to thrombosis are unclear, but is thought to engage progressive platelet hyperactivity. We hypothesise that dysglycaemia joined; linked with poor glycaemic controils induces platelet hyperactivity. Insulin treatment of patients with diabetes is associated with dysglycaemia, and mainly with hyperglycaemia and hypoglycaemia variability. While chronic states of hyper or hypoglycaemia per se have a sensible effect on platelet activation through a degree of adaptation, we deemed that fast glucose variability such as from hyper to hypoglycaemia and often found in unsuccessfully, poorly controlled diabetic subjects may have a additionally deep effects on platelets leading to accumulative effects.
In this project we will observe the effect of glucose variability on platelet function and thrombosis. Using hyperinsulinaemic euglycaemic clamp established in our laboratory we will reproduce, simulate rapid changes in blood glucose levels in both type 2 diabetes and control subjects. We will examine (i) how rapid changes in glycaemic index alter platelet sensitivity to activators and inhibitors in whole blood, (ii) whether the platelet hyperactivity is because of a primary platelet defect or an alteration in the plasma environment, and (iii) study the role of specific ligands in mediating hyperactivity. These statistics will provide novel information on the prospective role of glucose variability in the pathobiology of diabetes.
This studentship provides an outstanding opportunity to receive training in both clinical simulation of dysglycaemia, basic cell and molecular biology techniques, methods (immunoblotting/, flow cytometry, fluorescence/confocal microscopy, platelet functional assays).
Location:
- The academic work will be based in HYMS Centre for Cardiovascular and Metabolic Research at the University of Hull campus.
Research Culture:
The student will join a research team that develop multidisciplinary approaches to identify, recognize latest means, mechanism regulating platelet function and find out if these newly identified mechanisms can be aims for prevention and treatment of arterial thrombosis associated with metabolic and cardiovascular diseases.
Named Academic:
The primary supervisor for this project is Professor Stephen Atkin (Stephen.atkin@hyms.ac.uk). Keenly interested applicants can informally consult with Professor Atkin about the project.
Financial support:
Each full-time UK/EU PhD scholarship will include fees at the ‘home/EU’ student rate and maintenance (£13,590 in 2012/13) for three years and the international fee bursaries will cover full tuition fees for full time overseas students for three years, depending on satisfactory progress. Financial assistance for conference attendance will also be available. The international fee bursaries will cover full tuition fees for full-time overseas students for three years, depending on satisfactory progress.
Start date:
- This scholarship is expected to start in October 2012.
Qualifications required:
- A 2:1 degree or higher (or equivalent) in a relevant degree subject.
How to apply:
- All applications MUST BE submitted to the HYMS Postgraduate Centre via the online application method:
Please quote ‘HYMSPG/10/1213′ with the scholarship title when applying. In order for the Panel to obtain a sense of your academic background, obligation and interest, you are essential to complete the application form in full and provide a research proposal/outline of academic interest. If you have any queries on how to apply please email postgraduate@hyms.ac.uk.
Interview date:
Interviews for the scholarship will be held as soon as possible after the closing date. Applicants who are shortlisted for interview will be sent details of the date, time and location via email within a week of the closing date. If you are not invited for the interview, it means that your application has not been successful. Please note that we do not offer feedback to applicants who are not called to the interview.
Interview result:
As soon as sensibly feasible after the interviews have taken place HYMS will write to the successful applicant offering him/her the position. Upon receipt of formal written acceptance of the post we will write to inform unsuccessful candidates. At the same time as we try to do this in as effective and efficient way as possible, sometimes the process can take rather longer than is ideal because of the need to recall candidates for a second interview and reconvene interview groups and/or because of schedule, routine disruptions caused by leave and other absences. We express regret for any delay and inconvenience caused in these situations.
Application Deadline: 2 March 2012