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The regulation of platelet function - towards new strategies to prevent thrombosis


   School of Biological Sciences


Reading United Kingdom Biochemistry Cell Biology Endocrinology Health Informatics Medicine Pathology

About the Project

Project Overview:

Platelets perform a pivotal role in the regulation of haemostasis, a physiological response to injury that prevents excessive bleeding. They also play a central role in thrombosis, the inappropriate formation of blood clots in the circulation that lead to heart attacks and strokes. Considerable progress has been made in increasing our understanding of the signal transduction mechanisms that positively regulate the function of these cells at sites of tissue damage, and negatively regulate their function in the undamaged circulation. A particular interest of the host our laboratory is understanding the complex interplay between activatory and inhibitory signalling mechanisms in platelets. It is believed that the fine balance between these dynamic mechanisms regulates the threshold stimulus strength required for thrombus formation, and limits the size of a developing thrombus, thereby localising platelet function to sites of injury where sub-endothelial collagen is exposed.   

A PhD project is available to study a newly- discovered cell communication mechanism that is utilised by platelets to regulate haemostasis and is also implicated in thrombotic disease. This study will focus on the signals that are present in the damaged and undamaged circulation, the receptors that they bind to on platelets and related cells, the channel-like proteins that through which the newly discovered communication mechanisms work, and the signal transduction mechanisms that ultimately control the functions of these cells in health and disease. This PhD will be in a clinically- important area of biomedical research and will provide specialist training in cardiovascular biology, a broad training in cell biology approaches and the translation of fundamental biomedical science into new preventative or therapeutic strategies. 

 

School of Biological Sciences, University of Reading:

The University of Reading, located west of London, England, provides world-class research education programs. The University’s main Whiteknights Campus is set in 130 hectares of beautiful parkland, a 30-minute train ride to central London and 40 minutes from London Heathrow airport. 

 Our School of Biological Sciences conducts high-impact research, tackling current global challenges faced by society and the planet. Our research ranges from understanding and improving human health and combating disease, through to understanding evolutionary processes and uncovering new ways to protect the natural world. In 2020, we moved into a stunning new ~£60 million Health & Life Sciences building. This state-of-the-art facility is purpose-built for science research and teaching. It houses the Cole Museum of Zoology, a café and social spaces.

In the School of Biological Sciences, you will be joining a vibrant community of ~180 PhD students representing ~40 nationalities. Our students publish in high-impact journals, present at international conferences, and organise a range of exciting outreach and public engagement activities.

During your PhD at the University of Reading, you will expand your research knowledge and skills, receiving supervision in one-to-one and small group sessions. You will have access to cutting-edge technology and learn the latest research techniques. We also provide dedicated training in important transferable skills that will support your career aspirations. If English is not your first language, the University's excellent International Study and Language Institute will help you develop your academic English skills.

The University of Reading is a welcoming community for people of all faiths and cultures. We are committed to a healthy work-life balance and will work to ensure that you are supported personally and academically.

Eligibility: 

Applicants should have a good degree (minimum of a UK Upper Second (2:1) undergraduate degree or equivalent) in Biomedical Sciences, Biological Sciences or a strongly-related discipline. Applicants will also need to meet the University’s English Language requirements. We offer pre-sessional courses that can help with meeting these requirements. 

 

How to apply: 

Submit an application for a PhD in Biological Sciences at http://www.reading.ac.uk/pgapply 

 

Further information: 

http://www.reading.ac.uk/biologicalsciences/SchoolofBiologicalSciences/PhD/sbs-phd.aspx 

 


Funding Notes

If you have the correct qualifications and access to your own funding, either from your home country or your own finances, your application to work with this supervisor will be considered.

References

Gaspar, R.S., Sage, T., Little, G., Kriek, N., Pula, G. Gibbins, J.M. (2021) Protein disulphide isomerase and NADPH oxidase 1 cooperate to control platelet function and are associated with cardiometabolic disease risk factors. Antioxidants, 10, 497.
Holbrook, L-M, Keeton, S.J., Sasikumar, P., Nock, S., Gelzinis, J., Brunt, E., Ryan, S., Pantos, M.M., Verbetsky, C.A., Gibbins, J.M. and Kennedy, D.R. (2020) Zafirlukast is a broad-spectrum thiol isomerase inhibitor that inhibits thrombosis without altering bleeding times. Brit J Pharmacol, 178, 550-563.
Sahli, K.A., Flora, G.D., Sasikumar, P., Maghrabi, A.H. Holbrook, L-M, AlOuda, S.K., Elgheznawy, A., Sage, T., Stainer, A.R., Adiyaman, R., AboHassan, M., Crescente, M., Kriek., N., Vaiyapuri, S., Bye, A.P., Unsworth, A.J., Jones, C.I., McGuffin, L.J., and Gibbins, J.M. (2020) Structural, Functional and Mechanistic Insights Uncover the Fundamental Role of Orphan Connexin62 in Platelets. Blood: 137, 830-843.
Unsworth, A.J., Bye, A.P., Sage, T., Gaspar, R.S., Eaton, N., Drew, C., Stainer, A., Kriek, N., Volberding, P.J., Hutchinson, J.L., Riley, R., Jones, S., Mundell, S.J., Cui, W., Falet, H. and Gibbins, J.M. (2021) Anti-platelet properties of Pim kinase inhibition is mediated through disruption of thromboxane A2 receptor signalling. Haematologica. 107, 1968-1978.
Bye, A.P. Unsworth, A.J., Desborough, M.J., Hildyard, C.A.T., Appleby, N., Bruce, D., Kriek, N., Nock, S.H., Sage, T., Hughes, C.E., and Gibbins, J.M. (2017) Severe platelet dysfunction in NHL patients receiving ibrutinib is absent in patients receiving acalabrutinib. Blood Adv, 1, 2610-2623.



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