• Wellcome Trust Centre for Cell-Matrix Research, Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Michael Smith Building, Oxford Road

    M13 9PT Manchester

    United Kingdom

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Personal profile

Biography

Tony Day is a Professor of Biochemistry within the Faculty of Biology, Medicine and Health, The University of Manchester, UK. He is part of the leadership team of the Wellcome Trust Centre for Cell-Matrix Research (Lead for Translation) and a member of the Lydia Becker Institute of Immunology and Inflammation. 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 a matrix biologist with a major interest in the role of glycosaminoglycan-protein interactions during inflammation and ovulation. 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. This has provided important insights into the molecular basis of hyaluronan recognition by proteins and underpins the development of TSG-6 as a biological drug.

Tony has published over 180 scientific papers (H-Index 68 on Google Scholar; 43 papers with citations ≥100) and currently has funding from the BBSRC, Fight for Sight, the Macular Society, MRC, Versus Arthritis and the Wellcome Trust. He is a member of Versus Arthritis’s College of Experts (2016-present) and previously served on the MRC's College of Experts  (2005-2009) and the Editorial Boards of the Journal of Biological Chemistry (2001-2006) and Matrix Biology (2016-2019). Tony was elected to the Academy of Europe in 2012, is a former member of the Council of the International Society for Matrix Biology, was Chair of the Gordon Research Conference on Proteoglycans in 2018 and is President of the International Society for Hyaluronan Sciences.

Research interests

Glycosaminoglycan-protein interactions in inflammatory processes

My main area of interest is the role of glycosaminoglycan-binding proteins in inflammatory disease (e.g. arthritis and age-related macular degeneration) and inflammation-like processes (e.g. ovulation). Glycosaminoglycans (GAGs) are linear polysaccharides that are key components of 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 properties of cartilage and blood vessel walls, the formation of a viscoelastic “cumulus” matrix around the oocyte that is required for ovulation/fertilisation as well as mediating immune cell trafficking. One of the long-standing aims of our research is to determine the structural basis and molecular regulation of HA-protein interactions. We have already made significant progress on this, for example, through X-ray crystallographic and NMR analysis of TSG-6, a secreted protein often associated with inflammation, and CD44, the major cell surface receptor for HA. We are also using biophysical techniques such as AUC, SEC-MALLS and SAXS to help characterise multi-molecular hyaladherin/HA complexes and provide models for non-HA-binding proteins that are implicated in HA matrix organisation, e.g. PTX3. In addition to HA, TSG-6 binds to sulphated GAGs (i.e. chondroitin-4-sulphate, dermatan sulphate (DS), heparan sulphate (HS) and heparin) as well as a growing list of proteins (e.g. CXCL8, inter-α-inhibitor (IαI) and RANKL) where these interactions underpin a wide range of different functional activities. For example, TSG-6 catalyses the covalent transfer of heavy chains from IαI onto HA to form HC•HA complexes that are essential for the formation/stability of the cumulus matrix and where this modification of HA can also occur at sites of inflammation; our recent studies have shown that PTX3 plays a critical role in cross-linking these HC•HA complexes to form a stable network. Furthermore, TSG-6 has been shown to be a potent inhibitor of neutrophil migration (via its binding to CXCL8), protect cartilage in models of inflammatory arthritis and has been implicated in the regulation of bone turnover (e.g. inhibiting osteoclast-mediated bone resorption). 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. Another key area of interest is the investigation of 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 (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 of CFH to sulphated GAGs, e.g. HS and DS present in the Bruch’s membrane of the human retina, which is the site of AMD pathology. In addition, we have recently found that this 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.

For further details see http://www.wellcome-matrix.org/research_groups/tony-day.html

Overview

Inflammation is part of our body’s natural defence against infection and is required to successfully heal wounds. However, if inflammation continues unchecked (and becomes chronic) then damage to our tissues occurs; for example, as is seen in the joints of individuals with arthritis. It is our aim to better understand the molecular processes that occur during inflammatory diseases. This includes investigating the role of the innate immune system in a major form of blindness (AMD) and how a protective mechanism, triggered by acute inflammation, may serve to prevent cartilage and bone breakdown. A major focus for our studies is a type of sugar that is found on all cell surfaces and in the extracellular matrix of every tissue. These so called, GAGs, determine the location and functions of protein molecules and therefore play a key role in human biology and disease. We are also studying the role of GAGs and GAG-binding proteins in mammalian ovulation – a process that has some things in common with inflammation – in order to understand whether defects in ECM formation underlie infertility in humans. For further details see: http://www.wellcome-matrix.org/research_groups/tony-day.html

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being
  • SDG 10 - Reduced Inequalities

Education/Academic qualification

Master of Arts, Oxford University

… → 1989

Doctor of Philosophy, Oxford University

19851988

Bachelor of Arts, Chemistry, Oxford University

19811985

Research Beacons, Institutes and Platforms

  • Manchester Regenerative Medicine Network
  • Lydia Becker Institute
  • Christabel Pankhurst Institute

Keywords

  • Inflammation
  • Extracellular Matrix
  • protein biochemistry
  • glycosaminoglycans
  • osteoarthritis
  • osteoporosis
  • age-related macular degeneration
  • ovulation
  • structural biology

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