Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

FUNDED PhD: Dr Ingmar Schoen - Thrombosis and Vascular Biology

The aim of this PhD project is to better understand the heterogeneity within the platelet population.

Project title

Contribution of platelet biomechanics to the functional diversity of platelets

Project description

Platelets are small anucleate cells in the blood stream. They have important functions in haemostasis by adhesion to the injured vessel wall and to each other, as well as by secrection of coagulatory factors. How these mechanical and biochemical functions are linked on the level of single platelets has remained elusive due to the lack of appropriate technologies to study single platelets.

Our current understanding of platelet function is largely based on bulk measurements. In recent years however, evidence has accumulated that distinct subsets of platelets have distinct functions. Anti-platelet treatments to manage the risk for thrombosis or severe bleeding thus may need to be targeted to a specific subpopulation.

Recently developed high-throughput fluorescence and traction force microscopy techniques open up exciting new avenues to study the relevant processes on the single cell level.

The aim of this PhD project is to better understand the heterogeneity within the platelet population. The primary emphasis will be on platelet contractility and related features (such as cytoskeletal morphology). The secondary aim is to correlate biomechanical with biochemical functions (such as platelet granule secretion or PS exposure) on the level of single platelets. 

The successful candidate will learn traction force microscopy and other techniques to measure platelet contractile forces and to correlate these with underlying protein expression levels or secretory activity. To this end, she/he will establish a protocol to functionalise and pattern surfaces for cell adhesion, develop appropriate labelling strategies to measure the expression of specific markers in platelets, and pursue high-throughput platelet aggregometry assays. Moreover, advanced image and data analysis will be employed to extract differences in platelet behaviour based on ligand identity or different stimulants, or between platelets from healthy donors and from patients with diagnosed platelet disorders. The final goal is to establish characteristic metrics to distinguish platelet subpopulations, for discriminating physiological from pathological behaviour. 

This project bridges the fields of molecular cell biology, mechanobiology, biophysics, microscopy, bioengineering, and cardiovascular diseases. It is expected that the successful candidate has a strong background in one of these fields and is willing to cross the borders between disciplines. In our lab, we want to create and foster a friendly, supportive, and productive atmosphere to perform innovative research. An open communication and everyone’s commitment to this goal are very important to us. If you are motivated to join the effort, we are looking forward to your application. 

  • Department: Molecular and Cellular Therapeutics
  • Funding agency: RCSI StAR Programme
  • Tenure: Four years
  • Salary: Stipend of €18,000/year up to a maximum of four years, StAR programme. Fees will be covered by RCSI for exceptional candidates.

Specification

The successful candidate should be able to demonstrate the following:

Essential

  • An Honours Bachelor degree (grade 2.1 or above) in the natural sciences (biology, physics), bioengineering, or interdisciplinary study programmes
  • Open and direct communication
  • A high motivation to develop scientific thinking, experimental and problem-solving skills throughout the duration of the project
  • Ability to work on one’s own initiative and to organise yourself
  • Willingness to work together with scientists from different disciplines
  • English language requirements for candidates who do not speak English as their first language: an IELTS score of 6.5 or above

Desirable:

  • Pre-experience with microscopy techniques, cell culture, or blood handling
  • Programming skills (MATLAB).

 

Application process

Please apply with an up-to-date CV, a 500-word statement outlining your interest in and suitability for the position, and – if possible – contact details of two referees to ingmarschoen@rcsi.ie.

  • Application deadline: Friday, 1 December 2017 and afterwards on a rolling basis
  • Interview date: December 2017/January 2018
  • Start date: 1 February 2018 or later

Mentors Dr Ingmar Schoen