Investigating neutrophil heterogeneity in ANCA-associated vasculitis

Stipend: Standard Research Council London Rate + Tuition Fees (Home rate) for 3 years. A consumables budget is also provided.

Applications are invited for a 3-year PhD studentship based in the Centre for Inflammatory Disease at Imperial College London. The aim of the studentship is to investigate the role of neutrophil heterogeneity in the pathogenesis of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), the most common cause of crescentic glomerulonephritis.

About the Project

In this post you will work on an exciting research project investigating neutrophil heterogeneity in ANCA associated vasculitis (AAV). AAV are a group of systemic autoimmune diseases in which neutrophils are both target of the autoantibody and mediators of vascular injury. Neutrophils are classically thought to be a homogenous short-lived population with limited transcriptional activity. However recent studies have led to increasing appreciation of neutrophil heterogeneity in health and disease, including the presence of low-density granulocytes, first described in SLE and since recognised in several inflammatory and immune conditions, including AAV. The overarching aim of this project is to understand how functional and biophysical differences in neutrophil subsets contribute to disease pathogenesis and differing clinical phenotypes, organ tropism, and treatment response in AAV.

Key aims are to:

(i) Identify the biophysical and functional properties of neutrophil subsets in patients with AAV

(ii) Determine if these neutrophil subsets can be induced by ANCA stimulation in vitro

(iii) Characterise neutrophil subsets at sites of tissue inflammation in AAV

The student will use biophysical and functional assays to assess responses of healthy neutrophils treated with ANCA, alongside neutrophils from patients with active and quiescent AAV.  As part of this project the PhD student will receive extensive training in a broad range of molecular biology techniques, neutrophil and other primary human cell culture, co-culture assays, multiparameter flow cytometry, cell sorting, confocal fluorescence microscopy, and real-time deformability cytometry, a novel technique for the assessment of biophysical properties of cells. Immunostaining and spatial molecular imaging will also be explored.

Candidates are encouraged to contact Dr Maria Prendecki ([Email Address Removed]) to discuss their application.

How to Apply

This is a 3 year, full-time, fully-funded studentship, funded by the Auchi renal research fund. The studentship will commence in October 2023. Applicants must hold a first or upper second-class honours degree (or equivalent overseas qualification) in a relevant area of biology, biochemistry, or physiology from a recognised academic institution. Completion of a Masters degree by the start date of the PhD is desirable but not essential.

Applicants are requested to send a full CV (including the names and email addresses of two academic referees), and personal statement detailing why you are interested in the research project (maximum 1 side A4, font size 12 Arial) to Edward Wallace ([Email Address Removed]). The successful candidate will be asked to complete an electronic application form at Imperial College London to allow their qualifications to be reviewed by College Registry.