Tony Day is a Professor of Biochemistry within the Faculty of Biology, Medicine and Health. He is a member of the Manchester Cell-Matrix Centre, where he is Lead for Translation (since 2016). Tony is also the Chief Scientific Officer (CSO) of Link Biologics Ltd, a University of Manchester spinout company.

During his early career he was based at the University of Oxford where he obtained a BA in Chemistry (1985) and a DPhil in Biochemistry (1988). Between 1988-1998 Tony was a Research Fellow within the Department of Biochemistry, University of Oxford. In 1998 he became a member of MRC Senior Scientific Staff within the MRC's Immunochemistry Unit (Oxford). In October 2005 he took up his current post at the University of Manchester. Tony is located within the Division of Cell-Matrix Biology and Regenerative Medicine as well as being a member of the Lydia Becker Institute of Immunology and Inflammation. He has served as the Academic Lead for the BioMolecular Analysis core facility since 2008.

Tony is a matrix biologist with a major interest in the role of glycosaminoglycan-protein interactions during inflammation and ovulation. For example, he has published seminal papers on hyaluronan-protein interactions, including structural/biophysical studies on the major hyaluronan (HA) receptor CD44 and the inflammation-associated protein TSG-6, providing important insights into the molecular basis of hyaluronan recognition by proteins. Moreover, Tony has made a major contribution to understanding the biochemistry of how TSG-6 mediates the covalent modification of HA with heavy chains (HC) of the inter-alpha-inhibitor family of proteoglycans and the role of this process in cumulus expansion (essential for ovulation). His insights into the formation and composition of HC•HA complexes are helping to define novel inflammatory mechanisms with implications for understanding diverse disease processes including virus-induced lung pathologies. Recent work has determined the canonical structure for HCs and characterized how HC•HA form a crosslinked matrix via their interactions with the octameric protein pentraxin-3.

Underpinned by his >30 years of research on the TSG-6 protein, Tony is developing a biological drug, ‘Link_TSG6’ that has wide applicability for inflammatory and tissue-degenerative diseases. To take this forward, Tony (along with his long-term collaborator Dr. Caroline Milner, and business partner, Reuben Dawkins) founded Link Biologics Ltd, which was spun out from the University in 2021. This was based on pre-clinical data for dry eye disease (DED) and osteoarthritis, conditions that each affect 100s of millions of individuals worldwide.

Tony has published over 200 scientific papers (H-Index 86 on Google Scholar; 74 papers with ≥100 citations) and currently has funding from the BBSRC (sLoLa), Versus Arthritis (programme grant) and the Wellcome Trust (Discovery Award). Tony is on the Senior Advisory Board of Proteoglycan Research (from 2022) and is a member of the Kidney Research UK College of Experts (from 2025). Previously he served on the MRC’s and Versus Arthritis’ College of Experts (2005-2009 and 2016-2022, respectively) and the Editorial Boards of the Journal of Biological Chemistry (2001-2006) and Matrix Biology (2016-2019). Tony is a former member of the Council of the International Society for Matrix Biology (2016-2019), was the Chair of the Gordon Research Conference on Proteoglycans in 2018 and served as President of the International Society for Hyaluronan Sciences (ISHAS) between 2020-2023. Tony was elected to the Academy of Europe in 2012 and the Academy of Medical Sciences in 2025 and was recently awarded the 2025 Rooster Prize by ISHAS for his work on the structure, function and biotechnological applications of hyaluronan-binding proteins.

Research interests: Glycosaminoglycan-protein interactions in inflammatory processes

Tony Day’s main area of interest is the role of glycosaminoglycan-binding proteins in inflammatory disease (e.g. age-related macular degeneration, arthritis and various lung pathologies) and inflammation-like processes (e.g. ovulation). Glycosaminoglycans (GAGs) are linear polysaccharides that are key components of the extracellular matrix as well as being found ubiquitously on cell surfaces. For example, the interactions of hyaluronan (HA) – a high molecular weight GAG – with specific HA-binding proteins (hyaladherins) are responsible for the mechanical and biological properties of cartilage, brain structure (including perineuronal nets), formation of a viscoelastic ‘cumulus’ matrix around the oocyte (required for ovulation/fertilisation) and mediating immune cell trafficking; see https://doi.org/10.1002/pgr2.70007.

Over the last 30 years, the Day lab have made significant progress in determining the structural basis and molecular regulation of HA-protein interactions. For example, we have used NMR spectroscopy and X-ray crystallography to determine the structures of the Link module of TSG-6, a secreted protein often associated with inflammation, and the HA-binding domain of CD44, the major cell surface receptor for HA. Recently we have determined the crystal structure for a prototypical heavy chain (HC1) from the inter-alpha-inhibitor (IaI) family of proteoglycans and the structure of pentraxin-3 using a combination of cryo-EM, crystallography and molecular modelling. Along with biophysical analyses this has provided insight into how HCs, which become covalently attached to HA via the enzymatic activity of TSG-6, interact with pentraxin-3 to form crosslinked matrices (e.g., in the context of ovulation). Work is now in progress to understand the role of covalent HC•HA complexes in the formation of either pathogenic or protective extracellular matrices in the context of various lung conditions, such as viral and nematode infections, and asthma.

As well as HA, TSG-6 binds to sulphated GAGs (i.e. chondroitin-4-sulphate, dermatan sulphate (DS), heparan sulphate (HS) and heparin) and to a growing list of proteins, including chemokines and growth factors, where these interactions underpin a wide range of different functional activities; see https://pubmed.ncbi.nlm.nih.gov/29362135/. For example, TSG-6 is a potent inhibitor of neutrophil migration (via its binding to CXCL8), protects cartilage in models of arthritis (suppressing aggrecanase and collagenase activities) and has been implicated in the regulation of bone turnover. Thus, TSG-6 is likely an endogenous protector of joint and bone function during inflammation making it an attractive target for the development of novel treatments for musculoskeletal disease. Importantly, most of TSG-6’s ligand interactions are mediated via its Link module domain and work over many years has shown that ‘Link_TSG6’ has great potential to be developed as a protein biological drug for inflammatory and tissue-degenerative diseases. In this regard, Link Biologics Ltd was spun out from the University of Manchester in 2021, with dry eye disease (DED) and osteoarthritis as its lead indications, entering into a >£200m partnership with Théa Open Innovation in 2023; see https://linkbiologics.co.uk/. Currently, Tony spends a significant proportion of his time in his role as CSO of Link Biologics.

Tony also has a long-term interest in studying other GAG-protein interactions. This has included investigating the role of complement factor H (CFH) in Age-related Macular Degeneration (AMD), which is the predominant cause of blindness in the industrialised world; the Y402H polymorphism in the CFH gene (on chromosome 1), first described by Tony in 1988, has been implicated as a major risk factor for developing AMD. We have shown that this Tyr to His coding change has a large effect on the binding specificity of CFH to sulphated GAGs, e.g. HS and DS present in the Bruch’s membrane (a penta-laminar ECM) of the human retina, which is a site of AMD pathology. In addition, we have found that there is a large reduction in the amount of HS present in the Bruch's membrane as a consequence of normal ageing. The poorer binding of the disease-associated 402H variant could lead to chronic local inflammation (due to complement dysregulation), contributing directly to the development and/or progression of AMD. More recently we have identified HC3 of the IaI family as the most upregulated protein in Bruch’s membrane in the context of early AMD for donors with high Chromosome 1 risk. Work is ongoing to understand the structural and functional role of HC3 in this common debilitating disease.

The Day lab, in collaboration with Judi Allen (University of Manchester), has also been investigating the GAG-binding properties of chitinase-like proteins (CLPs), which are often upregulated during inflammation and play an important role in the type-2 immune response, e.g., during nematode infections. These ~40-kDa proteins have evolved from chitinase enzymes but have lost their catalytic activity. Work is ongoing to better understand how CLPs contribute to tissue repair through their interactions with components of extracellular matrix.

For further details see https://www.manchester-matrix.org/people/tony-day/