About the Project
3-year NHLI-funded PhD studentship – commencing JAN 2021
Applications are invited for a 3-year PhD studentship under the supervision of Dr Maria Prendecki, Dr Katharine Lodge, Dr Andrew Cowburn, and Professor Edwin Chilvers in the area of neutrophil biology.
Background
The anti-neutrophil cytoplasm (ANCA) associated vasculitides (AAV) are systemic auto-immune diseases characterised by inflammation of small blood vessels. Neutrophils play a key role in the pathogenesis of AAV; they are both the target of the autoantibody and mediators of vascular injury. Areas of inflamed vasculature are also characteristically hypoxic, a stimulus which we have shown enhances the tissue damage capacity of neutrophils. Real Time-Deformability Cytometry (RT-DC) is an exciting novel technique which allows us to quickly and accurately identify mechanical cell signatures (e.g. cell size, deformability and roughness). These morpho-rheological changes are predicted to have profound implications for neutrophil transit through the vascular system. The goal of this project is to characterise the currently unknown morpho-rheological signature of AAV neutrophils and to understand how ANCA and/or hypoxia influence the mechanical properties of neutrophils to cause vascular damage.
The project
The student will use RT-DC and RNA-sequencing techniques to compare the morpho-rheological phenotype and transcriptional responses of healthy neutrophils, treated with ANCA and/or incubated under hypoxia, with neutrophils from active and quiescent AAV patients, and from patients with viral or bacterial infections. These experiments will be used to identify the mechanical properties distinct to AAV neutrophils that contribute to endothelial damage. Potential disease-modifying targets will then be modulated in cellular and animal models of autoimmune vasculitis, aiming to reduce or prevent neutrophil-mediated vascular injury. This project will provide in depth training in neutrophil and endothelial cell biology, mechanical cell phenotyping and autoimmune disease, using cutting-edge techniques, and is a project with high translational potential.
You will be working as part of a research team at the internationally-renowned National Heart & Lung Institute, Imperial College London, led by Dr Maria Prendecki, Dr Katharine Lodge, Dr Andrew Cowburn, and Professor Edwin Chilvers.
Please direct any enquiries to Dr Maria Prendecki, [Email Address Removed].
How to Apply
Applicants must hold a first or upper second-class honours degree or UK equivalent
in a relevant area of biology, biochemistry, or physiology from a recognised academic institution.
To apply please send to NHLI’s PGR Office [Email Address Removed]
• a CV with your grades clearly listed
• a one-page personal statement, identifying your suitability for the described project
• the names and addresses of at least two academic referees
The closing date for applications is 30th November 2020
Please note that candidates must fulfil College admissions criteria.
Funding Notes
This position is available as a fully funded PhD studentship, including 3 years of tuition fees (Home/EU candidates) and provides a 3-year, tax-free stipend at the standard Research Council London rate.
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