Korcsmaros Group

Network Medicine & Organoids


Introduction


The Korcsmaros Group combines computational approaches (network biology and AI) and experimental technologies (organoids and multi-omics) to study complex systems in the gut. Our goal is to understand biological systems related to gut homeostasis and to facilitate precision medicine and personalised microbial therapies in the field of inflammatory bowel disease (IBD). Our vision is that with the combination of systems biology 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. To achieve this vision, our aim is to work on the multi-omics analysis of gut organoids to create computational network models of key intestinal cells interacting with other host cells or with microbial products, and then validate the predictions in a patient-specific organoid testing system.


Past Projects


We developed gap-filling network biology resources on signalling pathways and autophagy regulation (such as SignaLink, AutophagyNet, CytokineLink, SalmoNet) that we provide for the community through Cyverse UK. We also developed multiple computational workflows and software platforms to carry out automated analysis of big data in multi-omics and precision medicine (including iSNP, MicrobioLink, and Sherlock). In the past, we worked with various experimental model systems, including C. elegans, human cell lines and mouse organoids, and developed new protocols to investigate gut organoids and host-microbe interactions.

These resources and methods provided the following significant biological insights:

We have summarized in multiple review papers the key aspects and opportunities of the main methodologies we use, including Network Approaches, Organoids, Big Data and IBD, Big Data and autophagy, studying host-microbe interactions with computational and with experimental approaches.


Current and Future Projects

Intestinal homeostasis is maintained by multiple cell types, including 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 our previous achievements and developed approaches, our multidisciplinary group aims 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. This approach provides a holistic, systems-level view of IBD-related processes in the gut, and will complement existing programs focusing on immune-therapies against IBD (ie., Crohn’s disease (CD) and ulcerative colitis (UC)). Another key approach we consider is the patient-specific nature of these observations. We plan to understand the differences between CD/UC patient subpopulations. 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 approaches 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.

We are collaborating with multiple groups to achieve these objectives including groups in our host institute at Department of Metabolism Digestion and Reproduction, Faculty of Medicine, Imperial College London as well as in our affiliated institute in the Quadram Institute. In particular, we have strategic collaborations with the following groups:



Overall pipeline of our methods.

For full-sized version, please click on the image.

Our work has been supported by the NIHR Imperial BRC, institute strategic grants from the Quadram Institute and the Earlham Institute

Recent News

I am honoured to be a new member in the Research Strategy and Funding Committee of @CrohnsColitisUK.
Looking forward to contributing to the work of Crohn's & Colitis UK, and to supporting #IBD patients and research.
https://t.co/5pyDrzWFSu
@ibdseb Thank you @ibdseb! Could not have been possible without a fantastic team and excellent collaborators
🎦 Recording of a talk @ImperialMDR Bioinformatics seminar where I summarized the #PrecisionMedicine, cell-cell & cell-microbe #network projects we have done in #guthealth & #IBD. There is a teaser at the end on the new @ImperialBRC #Organoid Facility. https://t.co/SgDNLgT1HM
We based BioCypher on three important concepts: Modularity, Transparency, and Ontology. You can read the preprint at https://t.co/mWEuWqdULs or read on for a TLDR. BioCypher is open source and welcomes contributions. 🤝

Resources

Omnipath

OmniPath is a database of molecular biology prior knowledge developed in Saez Lab and Korcsmaros Lab.

SignaLink 3.0

SignaLink is an integrated resource to analyze signaling pathway cross-talks, transcription factors, miRNAs and regulatory enzymes.

Autophagy Regulation Network

An integrated resource to analyze regulatory network of autophagy proteins.

Nrf2Ome

Integrated regulatory network of Nuclear Factor (erythroid-derived 2)-like 2 (NRF2).

SalmoNet 2.0

An integrated network resource containing regulatory, metabolic and protein-protein interactions. For 20 Salmonella strains classified as gastro-intestinal or extra-intestinal pathogens.

CytokineLink

A map of cytokine communication for inflammatory and infectious diseases.

Projects

Network Medicine Approaches in IBD

Inflammatory Bowel Disease (IBD) is a disorder of the human gastrointestinal tract characterised by inflammation of the gut mucosal layer and dysbiosis of the microbiome.

Multi-omics Analysis of Intestinal Organoids

In healthy individuals, the gastrointestinal tract relies on highly sophisticated intercellular interactions to sense, adapt and respond appropriately to its cells’ immediate and distant environments.

Analysing Host-Microbiome Interactions

The microbiome plays a vital role in maintaining host systems’ homeostatic (healthy) functions. Disrupting the healthy microbiota – by external (temperature, hygiene, etc.) or internal factors (inflammation, ageing, etc.) – causes a dysbiotic (unhealthy) state.

Mapping Autophagy Regulation in the Gut

Autophagy is a common recycling process in which cells degrade their unnecessary or damaged parts.

Systems-level Projects on COVID19

The SARS-CoV-2 pandemic has mobilised scientists around the globe to research all aspects of the coronavirus virus and the disease it causes (COVID-19).

Affiliations

Faculty of Medicine, Imperial College, London, United Kingdom

Earlham Institute, Norwich Research Park, Norwich, United Kingdom

Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, United Kingdom

Department of Genetics, Eotvos Lorand University, Budapest, Hungary