Immune System Regulated Metabolism Across Diseases

Bringing together some of the strongest groups from both York and Maastricht by bringing together  infectious disease and spatial transcriptomics research at York with imaging mass-spectroscopy and cancer research at Maastricht. This project established molecular imaging as a strong pillar for the imaging theme of the York-Maastricht Partnership’s first funding call.  

The project began in November 2019, and was also supported by significant industry contribution from Nanostring, an additional strength which highlights that there are opportunities in research translation as well as cutting-edge research.

The 3 year project’s aim was to try and understand the similarities between the cellular environment in both cancer and infectious disease, as it had become clear that the way our body fights cancers and infections are somewhat similar

Paul Kaye, Professor of Immunology at the University of York, commented “The exciting thing about the YMP project is that we’ve brought together two technologies, one based at each university that allows us to study   very complex cell interactions in space. Being able to see how cells talk to each other and talk to their neighbours without having to disassociate their tissues will provide novel insights into disease mechanism”.

Ron Heeren, Professor of Molecular Imaging at Maastricht University added “In addition to doing state-of-the-art science together, the YMP project brought us additional insights. We learned from each other's operational use of imaging facilities in doing truly interdisciplinary research. We have taken optimal advantage from the available unique infrastructure at both institutions to move science forward. Something which would not have been possible without the YMP funding”.

At the University of York they are trying methods which allow them to specifically look at how genes are expressed to enable the production of proteins that drive aspects of the immune response. One of the critical aspects of that immune response and how it is modulated during disease is to understand changes in the lipid composition of cells and so the mass spectrometry based imaging technologies at the University of Maastricht are used to examine the lipid composition of the same cell populations that York is looking at using their genetic analysis. What they hope to achieve is to bring the two sets of data together to understand how we go from gene expression into protein expression and how that modifies the lipid micro environment to change the immune response to infection and cancer.

Using this innovative approach has enabled them to use the same sample and very, very small amounts of material from a biopsy of any particular patient which really enhances the reproducibility of the study and the statistical power that we get from the data that is generated.

They have also extended their collaboration to colleagues at the Institute of Tropical Medicine in Belgium and through them they are working with colleagues in Ethiopia, so they now have global reach into disease endemic countries and are using these combined technologies to examine how different forms of infectious disease develop in Ethiopia. This was the impetus for another grant award of almost  a million euros from the Dioraphte Foundation, a Dutch foundation supporting research on skin disease.

Although the project’s full impact is yet to be seen, they have started to learn about the different processes that are taking place in tissues, and are starting to map those immune responses that drive those tissue responses. The group has to date published a methodological review and also the first description of the lipid composition of liver granulomas during Leishmania infection. 

It will be exciting to see how this research develops and the impact it could have on public and individual health could be huge.