The principal research aim of the Sutton group is to understand the molecular basis of allergy and asthma and to discover and exploit new targets for therapeutic intervention. The antibody IgE plays a key role, and its specific cell-surface receptors are part of a larger network of protein-protein interactions. Using X-ray crystallography and a variety of other biophysical techniques, the group is currently investigating the structures and functions of the components of the “IgE network” and the complexes that they form. A programme to identify small molecule inhibitors of these protein-protein interactions is also underway.
We have always had a broader interest in antibody structure and function, studying antibodies involved in auto-immune disease, and tracing the evolution of antibody structure through structural and functional analysis of avian IgY, the evolutionary precursor of mammalian IgG and IgE.
Another long-standing interest of the group is in the structures and mechanisms of action of enzymes responsible for antibiotic resistance, and here again, X-ray crystallographic studies are central to our research.
The X-ray studies are conducted both in-house and at the synchrotron Diamond Light Source.
The Sutton group is part of the Asthma UK Centre in Allergic Mechanisms of Asthma, and in addition to Programme Grant funding from both MRC and The Wellcome Trust, the group has been supported for many years by Asthma UK and has also received funding from BBSRC and EPSRC.
People
Postdoctoral Research Associate
Emeritus Professor of Molecular Biophysics
Professor for Antimicrobial Therapy
Projects
Antibody-receptor interactions in allergy and asthma
IgE antibodies play a central role in allergic diseases such as asthma, and their interactions with the cell surface receptors FcεRI and CD23 (FcεRII) mediate the presentation of allergens to the immune system, trigger hypersensitivity reactions, and regulate the production of IgE. We are studying the structures of these molecules and their interactions by a combination of X-ray crystallography, site-specific mutagenesis and a variety of physical techniques including surface plasmon resonance analysis of protein-protein interactions. By studying the way in which anti-IgE antibodies, including the clinically approved Omalizumab, bind to IgE-Fc, we are discovering dynamic and allosteric properties of IgE that may be exploited for therapeutic intervention. We are also investigating the structural basis of allergen recognition by IgE, including the possibility of unconventional, “superantigen-like” interactions, as well as the structure and function of the IgG4 antibodies that are produced in immunotherapy and act as natural blocking antibodies for the response to allergens. (Collaborators: Professor Hannah Gould, Professor Jim McDonnell and Dr Andrew Beavil (Randall Centre for Cell & Molecular Biophysics); also various members of the Asthma UK Centre in Allergic Mechanisms of Asthma).
Structure and mechanism of antibiotic resistance enzymes
One of the principal mechanisms by which bacteria acquire resistance to β-lactam antibiotics (penicillins, cephalosporins and carbapenems) is the production of enzymes that hydrolyse these compounds, and we have studied the metallo-β-lactamases that now pose such a serious threat to the efficacy of many β-lactams. We have also studied acetyl-transferase enzymes from Pseudomonas aeruginosa and other bacterial species, which are involved in other mechanisms of antibiotic resistance such as biofilm formation. Most recently we have solved the structure of a bacterial enzyme that can counter biofilm formation and offer a new route to recover the efficacy of conventional antibiotics. (Collaborator: Professor Annalisa Pastore, King's).
Evolution of antibody structure
We are studying the structure and function of avian IgY antibodies, as well as the most primitive antibody, IgM, to understand the evolution of mammalian IgG and IgE. An ancestor of present-day chicken IgY was the evolutionary precursor of IgG and IgE, which differentiated their structures and functions following a gene duplication event that did not occur in the avian lineage. Since IgY displays IgG-like properties despite its IgE-like architecture, by studying IgY we hope to learn about the particular determinants of IgE structure that are responsible for its unique functional properties associated with allergy. We are also studying IgE from the most primitive mammals such as the platypus to further trace the evolution of this key antibody molecule and to understand the emergence of its activities in allergic disease.
Publications
People
Postdoctoral Research Associate
Emeritus Professor of Molecular Biophysics
Professor for Antimicrobial Therapy
Projects
Antibody-receptor interactions in allergy and asthma
IgE antibodies play a central role in allergic diseases such as asthma, and their interactions with the cell surface receptors FcεRI and CD23 (FcεRII) mediate the presentation of allergens to the immune system, trigger hypersensitivity reactions, and regulate the production of IgE. We are studying the structures of these molecules and their interactions by a combination of X-ray crystallography, site-specific mutagenesis and a variety of physical techniques including surface plasmon resonance analysis of protein-protein interactions. By studying the way in which anti-IgE antibodies, including the clinically approved Omalizumab, bind to IgE-Fc, we are discovering dynamic and allosteric properties of IgE that may be exploited for therapeutic intervention. We are also investigating the structural basis of allergen recognition by IgE, including the possibility of unconventional, “superantigen-like” interactions, as well as the structure and function of the IgG4 antibodies that are produced in immunotherapy and act as natural blocking antibodies for the response to allergens. (Collaborators: Professor Hannah Gould, Professor Jim McDonnell and Dr Andrew Beavil (Randall Centre for Cell & Molecular Biophysics); also various members of the Asthma UK Centre in Allergic Mechanisms of Asthma).
Structure and mechanism of antibiotic resistance enzymes
One of the principal mechanisms by which bacteria acquire resistance to β-lactam antibiotics (penicillins, cephalosporins and carbapenems) is the production of enzymes that hydrolyse these compounds, and we have studied the metallo-β-lactamases that now pose such a serious threat to the efficacy of many β-lactams. We have also studied acetyl-transferase enzymes from Pseudomonas aeruginosa and other bacterial species, which are involved in other mechanisms of antibiotic resistance such as biofilm formation. Most recently we have solved the structure of a bacterial enzyme that can counter biofilm formation and offer a new route to recover the efficacy of conventional antibiotics. (Collaborator: Professor Annalisa Pastore, King's).
Evolution of antibody structure
We are studying the structure and function of avian IgY antibodies, as well as the most primitive antibody, IgM, to understand the evolution of mammalian IgG and IgE. An ancestor of present-day chicken IgY was the evolutionary precursor of IgG and IgE, which differentiated their structures and functions following a gene duplication event that did not occur in the avian lineage. Since IgY displays IgG-like properties despite its IgE-like architecture, by studying IgY we hope to learn about the particular determinants of IgE structure that are responsible for its unique functional properties associated with allergy. We are also studying IgE from the most primitive mammals such as the platypus to further trace the evolution of this key antibody molecule and to understand the emergence of its activities in allergic disease.
Publications
Our Partners
Biotechnology & Biological Sciences Research Council
The Engineering and Physical Sciences Research Council (EPSRC)
Group lead
Emeritus Professor of Molecular Biophysics