19 February 2014, 12pm-1pm, GLT4, Warwick Medical School Building, University of Warwick
Title: 'Tinker Tailor Soldier Cell – The Role of Complex Carbohydrates in Host-Pathogen Interactions and Inflammatory Control'
Glycomics - the study of complex carbohydrates and their functions within biological systems, represents a major facet of post-genomic investigation. Many dangerous pathogens possess complex carbohydrate structures on their surfaces. Examples include viral glycoproteins such as HIV-gp120, bacterial peptidoglycans & lipopolysaccharides, and fungal cell wall glucans. Furthermore, pathogens express carbohydrate-binding proteins (known as lectins) that facilitate adhesion to host tissues and modulation of host immune responses. Similarly, mammals express a large array of carbohydrates and lectins that serve very broad physiological functions, including immunity.
A shared feature of chronic infectious diseases such as HIV and TB is the ability to exploit protein-carbohydrate interactions in order to sustain within-host survival in the face of efforts by the immune system to clear pathogens and restore tissues. Similar failure or subversion of host glycoimmunology may also contribute to other chronic infections such as the diabetic foot syndrome. This setting of prolonged attack/counterattack and persistent inflammation/tissue damage is reminiscent of the unhappy Cold War described very well in espionage novels!
Recent advances in glycomics and the development of sequence-controlled glycopolymers raise new possibilities for the understanding and engagement of oligosaccharides and lectins of the human immune system - with future benefits in inflammation and infection control. Solution NMR studies indicate the highly dynamic nature of an important human lectin, DC-SIGNR, and the power of this technique to resolve protein-carbohydrate and protein-polymer interactions at the atomic level. Meanwhile, advanced star-shaped glycopolymers designed for high affinity binding to the leukocyte lectins have been shown to bind to human monocyte-derived dendritic cells and influence cytokine production.
Dan's research carried out as part of the PhD degree (awarded in 2000 from Imperial College) involved the genetics of autoimmune disease and the role of innate immune mechanisms in autoimmunity and inflammation. This work was carried out with Marina Botto and Mark Walport. Postdoctoral work at the Oxford Glycobiology Institute with Kurt Drickamer involved the post-genomic study of protein-oligosaccharide interactions within the immune system, especially those encountered in HIV infection. Subsequent work with Bob Sim at the MRC Immunochemistry Unit in Oxford involved the investigation of the immune system in prion diseases such as scrapie and BSE. Several significant publications have emerged from these collective studies, including papers in Science and Nature Medicine.