MRC Protein Phosphorylation and Ubiquitylation seminar

Dr Joana Neves, Senior Lecturer in Mucosal Immunology, Kings College London, will give a talk on  “Complex organoid models to study gut cell interactions in health and disease”.

Your host will be Mahima Swamy.

Abstract

Intestinal homeostasis is dependent on appropriate interactions between various compartments including immune, mesenchymal, neural, epithelial and bacteria cells. Disrupt of these interactions can have local and systemic consequences and has been associated with the development of several diseases including, Inflammatory Bowel Disease (IBD), cancer and Parkinson Disease. Using intestinal organoids as a starting point, we built complexity into this model by adding other cellular components to be able to study these interactions in health and disease.  

Our studies on cultures of intestinal organoid with Innate Lymphoid Cells (ILC), a key mucosal immune player, demonstrated that epithelial cells provide a complex niche capable of supporting the final maturation of tissue specific ILC subsets. In addition, we showed that human gut ILC1 drive intestinal and extracellular matrix remodelling through production of TGFβ. This indicates the potential impact of ILC1 accumulation in IBD patients in driving intestinal cancer and fibrosis, two sequelae of IBD. We also identify a new module of interaction between ILCs and the intestinal epithelium: goblet cells provide Notch ligands that are essential for maintenance of NC3R+ ILC3 and for their production of IL-22. In turn, ILC3 drive intestinal epithelial cells towards a secretory phenotype.  

More recently, developed human neuron - intestinal organoid co-cultures to study the potential role of these interactions in the initiation of Parkinson disease. 

Taken together, our work provides unprecedented insight into in situ ILC maturation and function. Moreover, it introduces an organoid platform that provides exquisite control over both environmental stimuli and host genetics, making it powerful tool for dissecting immune, epithelial, stromal and neural interactions in health and disease. 

Biography  

Joana F Neves is a Senior Lecturer in Mucosal Immunology, group leader at King’s College London and 2023 Lister Institute of Preventive Medicine Prize winner.  

Joana did her PhD in immunology at Queen Mary University of London before moving to the Brigham and Women’s Hospital and Harvard Medical School to study immunological responses in colitis.  

In 2014, Joana joined King’s College London where she held a Marie Sklodowska Curie fellowship and a RCUK/UKRI Rutherford Fund fellowship before establishing her research group and becoming a Lecturer.  

Venue

Small Lecture Theatre: Medical Sciences Institute, School of Life Sciences