NWO Open Competition Domain Science-M2 funding for joint research on sugar barcodes instructing intestinal immune cells
Research news item
The Dutch Research Council (NWO) has awarded funding in the Open Competition Domain Science-M (ENW-M2) round for the joint project ‘Biosynthetic sugar barcodes to instruct intestinal immune cells’. This innovative project brings together two interdisciplinary research institutes to study molecular processes in the human gut. The project team led by biochemist Christian Büll from the Institute for Molecules and Materials (IMM) of the Radboud University, and immunologist Jochem Bernink from Amsterdam UMC, will study how complex sugar molecules called glycans influence the immune system of the intestine and play a role in inflammatory bowel diseases. “This grant enables us to study a fundamentally new concept of how complex sugar molecules are recognized by the immune system in the human gut ”, Büll says.
Inflammatory bowel disease
Inflammatory Bowel Disease (IBD) is becoming an increasing medical, economic, and societal burden in the Netherlands and worldwide. With limited effective treatments available, there is an urgent need to better understand the mechanisms that regulate intestinal health. While most research focuses on genetic and environmental factors, little is known about other internal signals that maintain immune balance in the intestine. A promising but understudied factor in intestinal immunity is the role of complex sugar molecules that reside on mucins—large proteins that form the protective mucus layer in the intestine. These sugars create unique molecular pattern, like barcodes, which carry crucial biological information that can be read by the immune system. However, how these sugar barcodes function and influence the immune responses remains largely unknown.
Mucin sugar barcodes
The project aims to explore how mucin sugar barcodes interact with immune cells in the gut, particularly innate lymphoid cells (ILCs) that are highly important for a balanced intestinal immune system. How the mucin sugar barcodes help maintaining a healthy immune system and how changes in the sugar pattern may lead to IBD will be addressed. The research team will apply innovative techniques to create different mucin sugar barcodes in the lab to see how immune cells react to them. They will also look at what factors control these sugar pattern and test whether adding ‘healthy’ barcodes to inflamed bowel tissue can reduce inflammation. The fundamental knowledge generated in this joint project can open new avenues for IBD treatment, offering innovative strategies to restore intestinal health and prevent disease progression. “This project will hopefully lead to a better understanding of the molecular signals that regulate the intestinal immune system and spark novel options for IBD treatment and gut health”, Bernink says.
Biomolecular Chemistry
In 2022, Büll started his own research group at the Biomolecular Chemistry department, focusing on unraveling the mechanisms of cellular glycosylation and biological interactions with glycans. Büll currently studies the complex biosynthesis of glycans in the intestine and aims to apply this knowledge to produce glycoproteins with novel functionalities. These kind of molecules can be applied to modulate the intestinal immune system and the intestinal microbiome. The department of Biomolecular Chemistry focuses on understanding autoimmune diseases like rheumatoid arthritis and Sjögren’s syndrome, emphasizing the role of B cells and the impact of post-translational modifications such as glycosylation on immunological self-tolerance. The research group is part of IMM.
About NWO Open Competition Science-M Domain
NWO Open Competition Domain Science-M (ENW-M) grants are intended for curiosity-driven scientific research of high quality. The grant offers researchers the opportunity to develop original, innovative, high-risk ideas and realize scientific innovations that can form the basis for the research themes of the future.
Contact information
Christian Bull, christian.bull [at] ru.nl (christian[dot]bull[at]ru[dot]nl)
