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

Non-funded PhD: Dr Ingmar Schoen

Dr Ingmar Schoen, Molecular and Cellular Therapeutics has two non-funded PhD opportunities available in the area of platelet research.

The Project one: ‘Does a mechanical feedback in platelets control thrombus growth?’

Platelets are small anucleate cells in the blood stream. Upon vascular injury, they adhere to vessel walls and aggregate to seal the lesion. At the same time, they secrete factors that positively enhance aggregation. It is poorly understood what limits this positive feedback loop. Getting a better understanding of this elemental process will open up the development of more efficient strategies against thrombosis.

Based on recent work by others and our own lab, we hypothesize that the sensing of mechanical properties by platelets co-regulates their aggregation response depending on their location within the developing thrombus. The successful candidate will learn bioengineering and advanced microscopy methods to establish an in vitro assay to study platelet aggregation on compliant substrates with tunable stiffness. Advanced image and data analysis, complemented by computational modelling, will be used to derive thrombus architecture and the functional state of individual platelets therein. Using various specific agonists and inhibitors, contributions from platelet adhesion, contractility, and from classical activation pathways to thrombus formation will be disentangled. The final goal is to link specific thrombus dynamics and architectures with pathological situations. The major clinical focus will be on patients that suffered a stroke and patients that take anti-platelet medication. 

The successful candidate should have a strong background in bioengineering or a natural sciences degree and is highly motivated to engage in interdisciplinary work. 

Keywords: Biomechanics, microfluidics, advanced microscopy

Research themes: Vascular biology, Biomaterials, Platelet biology, Vascular diseases

 

Project two: ‘Nanoscopy of granule secretion in platelets’

Platelets are the smallest blood cells that aggregate at injury sites to stop bleeding. As an important part of their function, platelets secrete substances in response to external signals. Recent data implied that secretion requires a functional actin cytoskeleton, but it remained unclear whether actin polymerization or rather actomyosin contractility may be involved. The structural regulation of the exocytosis of internal granules is not well understood. Experimental investigations of this process are difficult because of the small size of platelets (~3 µm) and the even smaller size of granules (100-500 nm). The dedicated super-resolution microscopy (SRM) expertise in the SchoenLab, which is unique in whole Ireland, enables us for the first time to investigate the coordination of specific molecules during this fundamental process.

The aim of this PhD project is to decipher the unclear role of the platelet’s cytoskeleton in granule secretion. The successful candidate will learn and develop labelling strategies of the secretion machinery in human platelets for super-resolution microscopy, perform STORM and PAINT measurements of platelet ultrastructure, and utilize advanced data analysis and particle averaging strategies to derive structural models of exocytic intermediate states. The final goal is to link specific perturbations and malignancies of the cytoskeleton and the exocytic machinery to 

We are seeking for candidates with a strong background in molecular biology and fluorescence microscopy or a training in biophysics. The successful candidate should be highly motivated to engage in interdisciplinary work and committed to scientific research.

Keywords: Super-resolution microscopy, exocytosis, thrombosis

Research themes: Vascular biology, Biomechanics, Imaging and Microscopy

 

Specification

This is an unfunded project. Prospective students with their own funding or those interested in jointly applying for funding are welcome to contact the PI (mentor), Dr Ingmar Schoen for further information. The candidate should have a strong background in bioengineering or a natural sciences degree and is highly motivated to engage in interdisciplinary work.

Mentors Dr Ingmar Schoen