Professor Max Crispin MBiochem, DPhil, MRSC, FRSB

Professor of Glycobiology

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Professor Max Crispin joined Biological Sciences from the Glycobiology Institute at the University of Oxford. He runs the Glycoprotein Therapeutics Laboratory which is predominantly focussed on developing anti-viral vaccines and new antibody-based therapies against cancer.

Understanding the structure and function of glycoproteins and how they can be engineered offers exciting routes to the development of new vaccines and therapeutics

Career History

Sept 2017-present: Professor of Glycobiology. University of Southampton, UK.

Oxford Glycobiology Institute, University of Oxford

May 2013-Aug 2017: Principal Investigator, Glycoprotein Therapeutics Laboratory.
Dec 2011-Aug 2017: University Research Lecturer.
Feb 2009-May 2013: Senior Research Associate, Laboratory of Dr Chris Scanlan.

Corpus Christi College, Oxford

Sep 2014-Aug 2017: Stipendiary Lectureship in Biochemistry, Director of Studies (Biochemistry).

Oriel College, Oxford

Feb 2017-Aug 2017: Senior Dean.
Sep 2014-Aug 2017: Against Breast Cancer Senior Research Fellow.
Sep 2008-Aug 2014: Fellow and Tutor in Biochemistry.
Sep 2007-Aug 2008: Lecturer in Biochemistry, Director of Studies (Biochemistry).

Division of Structural Biology, University of Oxford

Feb 2006-Feb 2009: Post-doc, Laboratories of Prof. E.Y. Jones FRS & Prof. D.I. Stuart FRS.

Academic Qualifications

2001-2005: DPhil in Biochemistry. University of Oxford, UK.

Research

Publications

Contributions

Enterprise

Contact

Research interests

Aim of research

In the Glycoprotein Therapeutics Laboratory we exploit the glycan modifications of proteins in the design of vaccines candidates and glycoprotein-based therapeutics. We have a particular interest in vaccine design against the Human Immunodeficiency Virus (HIV) and in the development of novel antibody-based cancer therapeutics. This involves understanding how glycans impact on protein and viral function, how they are structured, and how we they can be manipulated for therapeutic applications.

HIV immunogen design

Our work towards an HIV vaccine is based on targeting the carbohydrate coat of HIV that shields the virus. We have shown that this shield is different from normal “self” carbohydrates and is remarkably constant despite huge variation in the underlying protein. We have been investigating using microbial mimics of this shield to elicit antibodies that can protect against the virus.

Antibody therapeutics

Antibodies are incredibly versatile therapeutics and can exhibit both pro- and anti-inflammatory properties. For this reason, they are being applied to the treatment of conditions ranging from cancers to autoimmune disorders. Anti-cancer antibodies often rely on the recruitment of the immune system to cancerous cells through a constant region of the antibody termed the Fc region. We have structurally characterized how different glycans can impact on Fc structure and how they can be manipulated to fine-tune antibody effector functions. In addition, we are developing bispecific antibodies and a new approach for enhancing therapeutic antibodies against cancer that involves deactivating competing endogenous antibodies that can limit the potency of anti-cancer antibodies. We are very proud to be sponsored by Against Breast Cancer.

The fine structure of the glycan shield of the viral spike of a recombinant mimic of the Human Immunodeficiency Virus (HIV). — Glycan shield of the viral spike of a recombinant mimic of HIV

The fine structure of the glycan shiled of the viral spike of a recombinant mimic of the Human Immunodeficiency Virus (HIV). The glycans act to sheiled the virus from the host immune response but can be targeted by some individuals who develop broadly neutralysing antibodies. Therefore, much effort is being made in trying to develop vaccines candidates that contain glycans that mimic those found on the virus. The high density limits the natural processing of glycans from oligomannose structures (green) to complex-type glycans (pink). Left: The processing state of the individuals has been depicted on a model of the glycosylated trimeric spike. Middle: The trimeric structure limits processing and leads to an elevation of oligomannose-type glycans at the protomer interface. Right: the ‘mannose patch’ of HIV can be described as being composed of both an ‘intrinsic mannose patch’ where oligomannose glycans appear even when monomeric subunits are expressed in isolation, and a ‘trimer-associated mannose patch’ that is driven by the trimer structure.

Research group

Molecular and Cellular Biosciences

Affiliate research group

Institute for Life Sciences (IfLS)

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Articles

Book Chapters

Letters/Editorials

Marjoram, D., Cruz-leal, Y., Bernardo, L., Le, N. P. L., Crispin, M., Yu, X., ... Lazarus, A. H. (2017). Immunoglobulin G Fc glycans are not essential for antibody-mediated immune suppression to murine erythrocytes. Blood, 130(26), 2902-2905. DOI: 10.1182/blood-2017-06-793729
Crispin, M. (2015). Breaking the allergic response by disrupting antibody glycosylation. Journal of Experimental Medicine, 212(4), 433. DOI: 10.1084/jem.2124insight2
Crispin, M., Yu, X., & Bowden, T. A. (2013). Crystal structure of sialylated IgG Fc: Implications for the mechanism of intravenous immunoglobulin therapy. Proceedings of the National Academy of Sciences of the United States of America, 110(38). DOI: 10.1073/pnas.1310657110
Dalziel, M., Crispin, M., & Dwek, R. A. (2013). Directing stem cell differentiation with antibodies. Proceedings of the National Academy of Sciences of the United States of America, 110(44), 17608-17609. DOI: 10.1073/pnas.1317614110
Crispin, M. (2013). Therapeutic potential of deglycosylated antibodies. Proceedings of the National Academy of Sciences of the United States of America, 110(25), 10059-10060. DOI: 10.1073/pnas.1307776110
Bowden, T. A., Crispin, M., Jones, E. Y., & Stuart, D. I. (2010). Correction: Shared paramyxoviral glycoprotein architecture is adapted for diverse attachment strategies (Biochemical Society Transactions (2010) 38, 5 (1349-1355)). Biochemical Society Transactions, 38(6), 1723. DOI: 10.1042/BST0381723
Crispin, M., Stuart, D. I., & Jones, E. Y. (2007). Building meaningful models of glycoproteins [1]. Nature Structural & Molecular Biology, 14(5), 354. DOI: 10.1038/nsmb0507-354a

Reviews

Watanabe, Y., Bowden, T. A., Wilson, I. A., & Crispin, M. (2019). Exploitation of glycosylation in enveloped virus pathobiology. Biochimica et Biophysica Acta (BBA) - General Subjects. DOI: 10.1016/j.bbagen.2019.05.012
Seabright, G., Doores, K. J., Burton, D. R., & Crispin, M. (2019). Protein and glycan mimicry in HIV vaccine design. Journal of Molecular Biology. DOI: 10.1016/j.jmb.2019.04.016
Allen, J. D., Sanders, R. W., Doores, K. J., & Crispin, M. (2018). Harnessing post-translational modifications for next-generation HIV immunogens. Biochemical Society Transactions, 46(3), 691-698. DOI: 10.1042/BST20170394
Crispin, M., Ward, A. B., & Wilson, I. A. (2018). Structure and immune recognition of the HIV glycan shield. Annual Review of Biophysics. DOI: 10.1146/annurev-biophys-060414-034156
Dalziel, M., Beers, S., Cragg, M., & Crispin, M. (2018). Through the barricades: overcoming the barriers to effective antibody-based cancer therapeutics. Glycobiology, 28(9), 697-712. DOI: 10.1093/glycob/cwy043
Behrens, A. J., & Crispin, M. (2017). Structural principles controlling HIV envelope glycosylation. Current Opinion in Structural Biology, 44, 125-133. DOI: 10.1016/j.sbi.2017.03.008
Dalziel, M., Crispin, M., Scanlan, C. N., Zitzmann, N., & Dwek, R. A. (2014). Emerging principles for the therapeutic exploitation of glycosylation. Science, 343(6166), [1235681]. DOI: 10.1126/science.1235681
Bowden, T. A., Crispin, M., Jones, E. Y., & Stuart, D. I. (2010). Shared paramyxoviral glycoprotein architecture is adapted for diverse attachment strategies. Biochemical Society Transactions, 38(5), 1349-1355. DOI: 10.1042/BST0381349

Professional Affiliations

Professor Adjunct, Department of Immunology and Microbiology, The Scripps Research Institute, California, USA
Fellow of the Royal Society of Biology
Supernumerary Fellow, Oriel College, Oxford.

Professor Crispin founded Immago Biosystems Ltd with Chris Scanlan in 2013. They invented a method to boost the cell killing activity of antibody-based cancer therapeutics. This has subsequently been shown to be effective in a variety of model systems including in human sera (ex vivo). Immago was subsequently acquired by Hansa Medical in 2016.

Professor Crispin performs consultancy for a range of biotechnology and legal firms principally in the area of glycoprotein-based therapeutics.

Professor Max Crispin
School of Biological Sciences
Faculty of Environmental and Life Sciences
Life Sciences Building 85
University of Southampton
Highfield Campus
Southampton
SO17 1BJ

Room Number: 85/3047

Professor Max Crispin's personal home page

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