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Supervisory Team

Professor I Greenwood 

Dr Isabelle Irène Salles-Crawley

Title of project

The importance of receptor signalling crosstalk in platelets

Find out more about this opportunity, including how to apply by clicking the headings below to reveal more information.


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Project details 

Platelets are anucleate blood cells that play an essential role in haemostasis (blood clotting). Whereas normal platelet function prevents us from bleeding in response to vascular injury, excessive platelet activation and blood clotting can cause myocardial infarction, stroke or deep vein thrombosis. Antiplatelet agents are widely used to diminish the incidence of these thrombotic disorders. Glycoprotein (GP) Ibα and GPVI are two of the major platelet receptors and are crucial to platelet function. Both receptors specifically interact with their respective ligands (von Willebrand Factor and collagen/fibrin) at sites of blood vessel damage. They also transduce cellular signals via tyrosine phosphorylation-dependent pathways leading to the activation of αIIbβ3 integrin that plays a crucial role in platelet aggregate formation. Although these receptors have different ligands, intriguingly, we recently uncovered a role for the intracellular domain of GPIbα in GPVI-mediated signalling events. This project aims to characterise the molecular mechanisms that underpin the cross-talk between these two platelet receptors. Our understanding of these processes will not only elucidate the mechanisms of platelet activation but may also provide new therapeutic opportunities for the prevention of cardiovascular disease.

We hypothesize that the intracellular tail of GPIbα specifically recruits signalling molecules involved in GPVI-mediated signal transduction in platelets.

The project involves 3 main aims:

1)     Identify the signalling molecules that associate with the tail of GPIbα that are required for GPVI activation in platelets

2)     Characterise GPVI-mediated signalling in GpIbαDsig/Dsig platelets that have a truncated GPIbα lacking the last 24 amino acids of the intracellular tail

Evaluate the importance of VWF-GPIbα signalling in thrombosis and haemostasis
Skills to be acquired

Isolating platelets, perform platelet function tests (flow cytometry, platelet aggregate formation under flow), become familiar with different molecular biology techniques (PCR, protein expression & purification, SDS-PAGE, western-blotting, immunoprecipitation) and fluorescence microscopy (widefield and confocal microscopy).

The student will give oral presentations and will train to answer questions from different audiences. The student will attend the Vascular Biology Research Section monthly meetings and national and international conferences in the field. Finally, the student will acquire scientific writing and critical thinking skills.

Entry requirements

Applicants should normally have an upper second-class honours degree (2:1) of a UK university or an overseas qualification of an equivalent standard obtained after a course of study extending over not less than three years in a university (or educational institution of university rank), in a subject appropriate to that of the course to be followed.

Students whose first language is not English must provide evidence of their skills as per the attached list

A national of a UKVI Majority English Language Speaking Country:(Antigua and Barbuda, Australia, the Bahamas, Barbados, Belize, Canada, Dominica, Grenada, Guyana, Jamaica, New Zealand, St Kitts and Nevis, St Lucia, St Vincent and the Grenadines, Trinidad and Tobago, USA, UK)

Not from majority English country but completed a qualification at least equivalent to UK Bachelor’s level degree according to UK NARIC in one of the below:Antigua and Barbuda, Australia, the Bahamas, Barbados, Belize, Ireland, UK Dominica, Grenada, Guyana, Jamaica, New Zealand, St Kitts and Nevis, St Lucia, St Vincent and the Grenadines, Trinidad and Tobago, USA          

British Council International English Language Testing System (IELTS).  For Postgraduate Research Degrees, SGUL accepts a minimum score of 6.5 overall (with no section less than 6.0)

Pearsons (PTE Academic) Test overall 64 (in all elements)

Cambridge English Advanced at level C1

Cambridge English Proficiency (Certificate of Proficiency in English) at C1 (minimum score of 45)

Funding
The successful applicant will receive a stipend for a three-year period and will have their fees paid for them during this time.  The studentship is open to both Home and Overseas students.  However, please note that,  if the successful candidate is overseas, they will be required to fund the difference between the Home fee rate and the Overseas fee rate.  For 21/22 the Home rate is £4,500 and the Overseas rate is £25,750 (we do not yet have the figures for later years).
How to apply

Please send the completed application form (Word) to researchdegrees@sgul.ac.uk by no later than 5pm on Friday 28th January 2022.  An equal opportunities form (Word) should also be submitted as a separate document.  You should ask your referees to complete the reference form (Word) and to submit them to the same email address by the same time, if possible.

Applications will undergo shortlisting and successful applicants will then be invited to interview over a two week period commencing 7th February 2022.

The successful candidate will be given a verbal offer and once it has been accepted, will be sent a formal offer letter and a registration pack with joining information.  The start date of the studentship will be 1st April 2022.

Unsuccessful candidates will be contacted with their outcomes at the earliest opportunity and will be able to request feedback if required.

 

 

 

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