A 2026 Crick PhD project with Zaeem Cader & James MacRae.

Project background and description

The incidence of autoimmune and chronic inflammatory diseases is increasing worldwide. For example, inflammatory bowel disease (IBD) now affects nearly 1 in 100 people in the UK and lacks curative treatment options [1]. Our previous work [2,3], along with several lines of genetic, epidemiological, and histopathological evidence emphatically point towards altered lipid metabolism as a critical driver of this disease. This is particularly relevant for Crohn’s disease, a major form of IBD characterised by transmural inflammation of the gut.

A striking feature of Crohn’s disease is the encasement of affected areas in a pathological fat layer known as ‘creeping fat’ [4]. Crohn’s is further associated with the development of organised clusters of immune cells (tertiary lymphoid follicles) that are themselves surrounded by fat adipose tissue. Likewise, mesenteric lymph nodes (key sites within the gut that maintain immune tolerance) are surrounded by perinodal adipose tissue. The composition, regulation, and functional role of the lipids at these sites is unknown. Importantly, we are yet to understand how these lipids contribute to the initiation and propagation of intestinal inflammation in Crohn’s disease.

This exciting inter-disciplinary PhD project will bring together technological and biological expertise to tackle this challenging, clinically-important question, with an equal split between immunological and analytical aspects of the study. The student will characterise the lipid architecture of the gastrointestinal tract, while using sophisticated metabolic labelling to assess lipid and redox metabolism. This will include harnessing the latest, state-of-the-art mass spectrometry (MS) instrumentation to establish new tools for unprecedented detailed characterisation of oxylipids – a lipid class of critical importance in gut health and immunological function. The project will use primary cell culture and immuno-competent organoid systems to functionally investigate how different lipid species and altered lipid composition affects immune cells and explore the biological mechanisms of lipid-immune interactions. The student will also use in vivo models of Crohn’s disease to experimentally test how lipids stemming from mesenteric lymph nodes and gut-associated lymphoid tissue shape immune responses to dietary and microbial antigens. This could potentially be further expanded to include patient samples. These approaches will bring new depth to our understanding of this debilitating disease and our findings could have broad ramifications for our understanding on the influence of diet on immune function. 

Zaeem Cader is a Clinician Scientist Group Leader at the Crick with a particular focus on immunometabolism and is a clinical expert in IBD. James MacRae is head of The Crick’s Metabolomics Science Technology Platform, where he uses a variety of MS instrumentation and is developing bespoke techniques to explore metabolism and lipid biology [5]. This project will allow the PhD student to gain expertise in the biology and physiology of immune and metabolic responses, particularly in relation to IBD. They will learn the fundamental MS techniques underpinning metabolomics and lipidomics and will drive development of novel technologies.

Candidate background

Candidates should have good knowledge of biology, biochemistry, and analytical chemistry. Knowledge of immunological disorders would be beneficial, but not essential. This project would suit highly motivated candidates wishing to learn and develop new MS techniques that enable impactful research into IBD. Pre-existing experience in standard laboratory protocols would be advantageous. Candidates will receive appropriate training and will be expected to work both independently and as part of a team.

References