T cell signalling in fibrotic feedback loops

About the project

About the Project Project Title: T cell signalling in fibrotic feedback loops Fibrosis is a pathological feature of many chronic inflammatory diseases, characterized by extracellular matrix (ECM) dysregulation, connective tissue accumulation, and complex immune-stromal feedback loops. Studies of cytotoxic (CD8) T cells in fibrotic tissues have revealed altered phenotypes and suppressed function, and there is evidence to suggest that while functional CD8 T cells can prevent or resolve fibrosis, their dysregulation in the fibrotic environment contributes to tissue decline. We are interested in the signalling mechanisms underlying the fibrosis-associated T cell state, specifically in the context of endometrial fibrosis. Endometriosis is a debilitating condition affecting 10% of women of child-bearing age that has no cure. The fibrotic tissue environment is a key feature of endometriosis and is characterized by particularly high levels of TGFb and dysregulated IL-15, which are known to regulate differentiation state, cytotoxic function, and both antigen-driven and antigen-independent activation of CD8 T cells. This project will examine the endometriosis-associated cytokine milieu, signalling of these cytokines in CD8 T cells, and the molecular mechanisms connecting this signalling to altered differentiation state and function. The project is a collaboration between the Richard Lab at the Babraham Institute and Cyclana Bio. The Richard Lab studies how T cell activity is altered by variations in antigen binding and the microenvironment 1-4 . Cyclana Bio is a biotech company with a mission to develop disease-reversing therapeutics to cure endometriosis. Cyclana also has strong academic roots in ECM biology 5 . The project will leverage the T cell expertise and experimental platforms from the Richard lab alongside endometriosis expertise and novel 3D tissue models developed by Cyclana Bio to examine the consequences of fibrosis-associated cytokine signalling in CD8 T cells. We are particularly focused on gaining mechanistic insight by identifying signalling, epigenetic, transcriptomic, and/or translational mediators of differentiation and functional effects. The student will have the opportunity to work in both industry and academic settings. They will be involved in all aspects of project planning, experimentation and analysis, with support from other team members. At Cyclana, the student will experience a small biotech working environment, contribute to work with clinical samples, and learn to use 3D tissue models with advanced tissue culture and imaging techniques. At the Babraham Institute, the student will benefit from a highly collaborative institute with collective expertise in Immunology, Signalling, and Epigenetics, and will have the opportunity learn a variety of immunological and genomic techniques including functional secretion and cytotoxicity assays, migration assays, signalling measurements, flow cytometry, single-cell and bulk transcriptomics, proteomics, CUT&Tag, CRISPR/Cas9 genome editing, and bioinformatic and statistical analysis of generated data. The student will share their research through publications and presentations at internal meetings and external conferences in both academic and industrial settings. Principal Supervisor Dr Arianne Richard Email address: Arianne.Richard@babraham.ac.uk Fully funded BioSCaPe iDLA Studentship URL link to personal profile page or website: Arianne Richard | Babraham Institute Further details about the BioSCaPe iDLA including how to apply can be found here The applications deadline for all PhD studentships: 8th December 2027 Please note interviews will be held the week commencing 18th January 2027 Students will not be able to take up an award unless they meet all University eligibility criteria and are successful in securing admission to the University. In addition, they will not be able to apply for a visa (if needed) until they hold an unconditional offer from the University. Incomplete applications will not be considered. Bioscience South Cambridge doctoral training Partnership (BioSCaPe) is a transformative PhD programme designed to create the bioscience leaders of tomorrow. Based in the heart of the world-leading Cambridgeshire bioscience cluster, BioSCaPe offers an unparalleled opportunity to combine cutting-edge research with entrepreneurial and leadership skills. BioSCaPe is a partnership between four world-leading research organisations; the Babraham Institute, Wellcome Sanger Institute, MRC Laboratory of Molecular Biology, and the University of Cambridge in collaboration with major industry partners including AstraZeneca, Illumina, Alloy Therapeutics, and others, alongside the Babraham Research Campus and its network of bioscience companies. Starting October 2027, 4-year Research Studentships will be available, leading to a University of Cambridge PhD degree, in the laboratories of Dr Jon Housley, Dr Teresa Rayon and Dr Arianne Richard at the Babraham Institute. Details of the Babraham Institute’s interactive scientific programmes can be found on www.babraham.ac.uk . As a student at the Institute, you will have access to all of the outstanding science facilities , each one providing specialist equipment and expertise to support key research techniques and technologies.

Research areas