Mucin (or mucin-like) proteins are proteins decorated with complex sugar structures (glycans), and form the basis of protective mucus layers in the gut and lungs. In the gut, mucins provide a substrate for the gut microbiome, which also uses them as a nutrient source, whilst in other tissues they act as signalling structures for immune cells. Sialic acid, a sugar at the end of glycans, plays a particularly important role in this. This thesis describes how the incorporation of sialic acid into glycans can be tracked within the cell, and how its production can be inhibited (locally). In addition, research has been conducted into how bacteria and immune cells recognise and utilise mucin proteins. For example, new proteins have been identified that bacteria use to recognise and degrade intestinal mucins, and investigations have been carried out into how the recognition of mucins by immune cells can be influenced by modifying the glycans. Research was also conducted into how a recently described cancer-associated sialic acid-recognising immune receptor recognises tumour cells, and what methods exist to disrupt this process through new therapies. This thesis demonstrates the importance of glycans on mucins for health, immunity and disease, and how they could potentially be used as therapeutic targets.
Daniel Hornikx (Nijmegen, 1996) graduated in Biology from Radboud University in 2020. During his Master’s degree in Medical Biology, he specialised in human biology. During his placements, he studied, amongst other things, the role of bacteria in the development of colorectal cancer and investigated ways to reduce inflammation associated with osteoarthritis. It was here that he first encountered glycosylation and the role of mucins in (gut) health. After completing his Master’s degree (2022), Daniël began his PhD at the Department of Biomolecular Chemistry, where, under the supervision of Dr Christian Büll, Dr Martin Jaeger and Prof. Ger Pruijn, he conducted research into mucin proteins and O-glycosylation. As part of this, he worked as a visiting researcher in the gastroenterology and internal medicine laboratories at Radboudumc. He is now continuing his career at ETH Zurich (Switzerland), where he is conducting research into mucin-degrading proteins from bacteria.