DrTamasKorcsmaros

We developed and currently maintain four resources that fill important gaps in the landscape of bioinformatics tools, and used by 1000s of researchers each month: 1) SignaLink; 2) Autophagy Regulatory Network; 3) NRF2ome; and 4) SalmoNet. SignaLink is an ELIXIR UK Roadmap resource and part of a UKRI-BBSRC e-Infrastructure National Capability. We co-developed OmniPath, which is the most comprehensive intra- and intercellular signalling network resource available. We recently introduced CytokineLink to study the role of cytokines in inflammatory and infectious diseases. These resources and accompanied pipelines are underpinning our future research projects.

For details on our resources, check our group website.

For details on our research project, check our group website.

In brief, our research projects, we are particularly interested in two key intestinal epithelial cell types, Paneth cells and goblet cells, producing antimicrobial peptides and the mucus layer, respectively, and shaping the microbiome and regulating how our cells are interacting with it. One of the key cellular processes in contributing to these functions is autophagy. Building on the achievements of my previous fellowship in Norwich, which included multiple systems-level and experimental studies on autophagy regulation, our multidisciplinary group combines computational approaches (network biology and AI) and experimental technologies (organoids and multi-omics) to investigate how autophagy is regulated in Paneth and goblet cells upon exposure to external stimuli from other host cells or microbes, and to decipher how host mutations often associated with IBD affect these intercellular and inter-kingdom cross-talks. We base our work on the multi-omics analysis of gut organoids, co-cultured with other host cells or relevant probiotic microbes such as Bifidobacterium. This approach provides a holistic, systems-level view of disease-related processes in the gut and will complement existing programs focusing on immune-therapies against digestive diseases. Another key approach we will consider is the patient-specific nature of these observations. We plan to understand the differences between IBD patient subpopulations by defining patient groups at risk of Paneth cell or goblet cell dysfunctions. Characterising patient group-specific alterations in interactions between host cells or between host cells and the microbiome; with a particular focus on interactions related to autophagy will lead us to provide the foundations of novel microbial and drug therapies.

With these projects we are addressing the complex questions of how key cells important for the intestinal homeostasis are regulated by other host cells or by gut microbes, how this regulation is changing upon IBD, and how we can use the identified knowledge to suggest novel therapeutic approaches for improving gut health.

Vision: With the combination of systems biology, microbiome phenotyping and precision medicine resources, we are going to understand better the patient specific nature of host-microbe interactions in the gut, and identify effective therapeutical options preventing the onset of IBD or relapse.

Aim: In order to achieve this vision, we base our work on multiple gut organoid models and their multi-omics analysis to create computational network models of gut systems, including Paneth cells and goblet cells interacting with other host cells or with microbial products, and then validate the predictions in a patient-specific organoid testing system.