Do Danger Associated Molecular Patterns (DAMPS) cause dysfunction of pluripotent stem cells differentiation, megakaryocyte maturation or proplatelet formation?
To celebrate the University's research successes, the University of Hull is offering this project supported by a full-time UK/EU PhD Scholarship or International Fees Bursary. It is one of a cluster of projects available as part of a significant investment into new and emerging areas of platelet research at Hull York Medical School's Hull campus
Closing date: - 29th February 2016.
Studentships will start on 26th September 2016
Supervisor: Dr Simon Calaminus (contact [Email Address Removed]) with Professor Khalid Naseem
Cardiovascular diseases are characterised by increased oxidative stress. In these diseases patients have increased circulating levels of oxidised lipids, called lipid peroxides, which are associated with plasma lipoproteins such as low density lipoprotein (LDL). Oxidation of LDL (oxLDL) converts it to a danger associated molecular pattern (DAMP) containing particle, which is highly proinflammatory and induces phenotypic changes in the cells it interacts with. In the blood it causes platelets to become hyperactive which can lead to increased thrombosis.
In addition to its effects within the blood, LDL can penetrate the blood vessel wall and influence cells outside the vascular system. One such cell is the megakaryocyte, which is descended from pluripotent stem cells, and is the precursor of blood platelets. The location of megakaryocyte maturation, development, and eventual initiation of platelet production is the subendothelial matrix, the area in which oxLDL and other DAMPs will be present. The oxidized phospholipids found in oxLDL have genomic effects that induce cell proliferation and increased invasiveness suggesting that accumulation of oxidised lipids in the blood vessel wall could change the phenotypic properties of the megakaryocyte. However the influence of oxidised lipids on megakaryocyte function and platelet function is completely uncharacterised. We hypothesise that elevated levels of oxidised phospholipids will induce alterations in megakaryocyte function, leading to platelet functional changes, which could underlie the hyperactivation of the platelet within patients with cardiovascular disease.
The student will use a wide range of biological assays, including transfection of primary megakaryocytes, spreading and migration assays, western blotting, pro-platelet formation, ploidy analysis via FACS, fluorescence and confocal microscopy in both 2D and 3D environments, to understand the effect of oxLDL on megakaryocyte function. It would suit a student with a background in biology, biochemistry, medicine or pharmacology. The student will join a team of post-doctoral scientists and PhD students who use multidisciplinary approaches to characterising molecular mechanisms regulating platelet and megakaryocyte function.
To apply for this post please click on the Apply button below.
In order to qualify for this scholarship you will require an undergraduate degree with at least a 2.1, or equivalent in a relevant subject.
Full-time UK/EU PhD Scholarships will include fees at the ‘home/EU' student rate and maintenance (£14,057 in 2015/16) for three years, dependent on satisfactory progress.
Full-time International PhD Fee Bursaries will include full fees at the International student rate for three years, dependent on satisfactory progress.
PhD students at Hull York Medical School follow modules for research and transferable skills development and gain a Masters level Certificate, or Diploma, in Research Training, in addition to their research degree.
Successful applicants will be informed of the award as soon as possible and by 30th April 2016 at the latest.