AZ Funded Non Clinical PhD Studentship - Macrophage-induced cytokines and cell cycle state in cancer and inflammatory diseases

Applications are invited for 4-year PhD studentship based in the Department of Medicine and the new AstraZeneca Discovery Centre (DISC) at Cambridge. The student will be working on a collaborative project jointly supervised by Prof Ravi Gupta and Dr. Daniele Corridoni at AstraZeneca offering the unique opportunity to work across the two sites, aiming to train independent, innovative scientists capable of pursuing translational research.

The project, entitled Macrophage-induced cytokines and cell cycle state in cancer and inflammatory diseases. is in the field of macrophages and their role in cancers and inflammatory diseases such as IBD that has generated much excitement in both academia and industry.

Project abstract: Macrophages have diverse phenotypes and functions depending partly on the microenvironment they reside in and play important roles in a range of conditions such as inflammatory arthritis, wound healing, cancer and infectious diseases. The biology behind heterogeneity in macrophage phenotypes is incompletely understood and the therapeutic potential of new insights into macrophage biology is enormous. We have built a body of work on the impact of cell cycle transitions on macrophage biology and identified that low oxygen conditions drive macrophages from G0 to G1 via a HIF2 directed transcriptional program with activation of the MEK/ERK proliferation pathway. We find secretion of IL1b, a pro-metastasis and pro-tumour molecule, is upregulated. This is pertinent given tumour associated macrophages are in a hypoxic environment. These observations are consistent with our data showing 'quiescent' G0 macrophages residing are highly sensitive to TLR4 activation compared to
those in G1. A recent paper linked blockade of macrophage inflammation mediated by ETS2 in inflammatory bowel disease using a cell cycle inhibitor (Nature 2024), though the mechanism remains unexplained. We will deploy a range of techniques to address the link between cell cycle regulation, tumourigenesis and inflammation. Our data could potentially be leveraged to modulate innate immune responses in diseases through drugs that modulate the cell cycle.

Full details of the University's entrance requirements and scholarships are specified on the following link: https://www.postgraduate.study.cam.ac.uk/.

Please ensure that you outline how you match the criteria for the post and why you are applying for this role on the online application form.

Please include details of your referees, including email address and phone number, one of which must be your most recent line manager.