MSc/PhD: Non-thrombotic functions of platelets

This project is an examination of the platelet secretome and its impact on wound healing and angiogenesis.

Project description

Circulating platelets in the blood play well-characterised, critical and complex roles in the regulation of thrombosis in response to injury and tissue-damage. Platelets contain dense granules and alpha-granules that each release their contents into the extracellular milieu, in response to local activation. The dense granules release ADP/ATP and pyrophosphate.

In contrast, the alpha granules store more than 300 active substances including cytokines, mitogens, pro- and anti-inflammatory factors and other bioactive molecules that are essential regulators in the complex microenvironment of the growing thrombus. In addition to their characterised role in the regulation of thrombosis, these bioactive agents also contribute to physiological processes such as wound-healing, angiogenesis and the pathophysiology of a number of diseases.

Platelet-rich plasma (PRP) is an easily-harvested resource from patients, and can be assessed as a potential diagnostic resource. In addition, it has recently been used as adjunctive therapy in a variety of different surgical scenarios, such as orthopedics and ophthalmology, where it serves as a growth factor pool for enhancing wound-healing and improving tissue regeneration. It also accelerates skin wound healing by promoting re-epithelialization

To date, there are a number of unanswered questions relating to the nature, functions and pathological relevance of the platelet's storage contents:

  • Does the platelet release response vary from person to person?
  • What are the contents (proteome) of the stored platelet contents?
  • Do the platelet storage contents vary from person to person?
  • Do the platelet storage contents vary in disease states?
  • Can the platelet contents serve as a predictive window for a therapeutic response?
  • Can autologous platelets provide a personalized source of wound-repair cytokines?
  • Can exogenous platelet releasate be used as a generic wound-healing resource?

Work in our lab has shown that the release of dense granule contents can vary from donor to donor by a factor of >10-fold; allowing us to stratify normal healthy donors into high responders and low responders. We have also demonstrated that platelets become hyper-responsive during pregnancy, responding to lower doses of naturally-occurring agonists and releasing a greater quantum of content from their dense granules.

This project will:

  1. Explore the impact of platelet alpha-granule releasates from normal healthy donors (both high and low-responders) in wound-healing and angiogenesis models.
  2. Examine the nature of the releasate components / fractions from platelet alpha-granules, that optimally impact on wound-healing and angiogenesis.
  3. Assess if natural food supplements such as vitamin D, or lifestyle indicators such as stress, can modulate the synthesis and release of critical cytokines in platelets.

Tenure: Four year PhD; or can be separated into shorter, distinct projects for an MSc.

Expected start date: October 2021

Note: Fees and laboratory costs are funded but no student stipend is available currently.

Specification

Minimum requirements: 

  • PhD: Upper second class (2.1) honours degree (or equivalent) in a relevant subject
  • MSc: Lower second class (2.2) honours degree (or equivalent) in a relevant subject

Desirable candidate specifications include:

  • An understanding of basic statistical analysis for quantitative studies would be an advantage

Application process

To apply, please complete the online application form in full.

Applications must include:

  1. Completed application form
  2. English language requirements – click here for more information

Deadline: 31 August 2021 at 17:00 

Please note:

  • Unfortunately, we are unable to provide individual feedback to applicants.
  • Shortlisted candidates will be invited for interview.
  • At this stage only successful candidates will be contacted to submit, CV, transcripts and other relevant documentation.
  • Only their referees will also be contacted at this stage for a reference.
  • It is the candidate’s responsibility to ensure the application form is completed in full on time. Late and/or incomplete applications will not normally be assessed.