Dr Max Crispin

Dr Max Crispin

Fellow and Tutor in Biochemistry

Dr Max Crispin, MBiochem, DPhil, MRSC.

I am based in the Oxford Glycobiology Institute within the Department of Biochemistry. My research interests lie in the development of carbohydrate-based vaccines against HIV and the development of therapeutic antibodies.  I am interested in how the carbohydrates attached to proteins (glycosylation) can be controlled and how such techniques can be exploited in the development of vaccines and therapeutics. For example, we have recently demonstrated a new approach for enhancing therapeutic antibodies against cancer (Baruah et al. J. Mol. Biol. 2012).  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 (Doores KJ et al. Proc Natl Acad Sci USA. 2010 and Bonomelli et al. PloS One 2011). We have been investigating using microbial mimics of this shield to elicit antibodies that can protect against the virus (Dunlop et al. Glycobiology 2010).

Teaching:

I oversee the teaching and admission of biochemistry students at Oriel. My teaching is generally focused in the areas listed. In addition, we often host 4th year MBiochem students in our laboratory several of whom have been co-authors to the papers listed below.

  • Biological Chemistry
  • Immunology & Virology
  • Glycobiology
  • Structure and Function of Macromolecules
  • Data Analysis and Interpretation
  • Biotechnology

Publications:

The carbohydrate shield of HIV and vaccine design

  • Pejchal R et al. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science. 2011 Nov 25;334(6059):1097-103. Epub 2011 Oct 13.
  • Bonomelli C, Doores KJ, Dunlop DC, Thaney V, Dwek RA, Burton DR, Crispin M, Scanlan CN. The glycan shield of HIV is predominantly oligomannose independently of production system or viral clade. PLoS One. 2011;6(8):e23521.
  • Doores KJ, Bonomelli C, Harvey DJ, Vasiljevic S, Dwek RA, Burton DR, Crispin M, Scanlan CN. Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens. Proc Natl Acad Sci USA. (2010) 107(31):13800-5. Read more here.
  • Harvey DJ, Sobott F, Crispin M, Wrobel A, Bonomelli C, Vasiljevic S, Scanlan CN, Scarff C, Thalassinos K, Scrivens JH. Ion Mobility Mass Spectrometry for Extracting Spectra of N-Glycans Directly from Incubation Mixtures Following Glycan Release: Application to Glycans from Engineered Glycoforms of Intact, Folded HIV gp120. Journal of the American Society of Mass Spectrometry. (2011) In press. 
  • Dunlop DC, Bonomelli C, Mansab F, Vasiljevic S, Doores KJ, Wormald MR, de Sa Palma A, Feizi T, Harvey DJ, Dwek RA, Crispin M, Scanlan CN. Polysaccharide mimicry of the epitope of the broadly neutralising anti-HIV antibody, 2G12, induces enhanced antibody responses to self oligomannose glycans. Glycobiology. (2010) Jul;20(7):812-23. Read more here. 
  • Scanlan CN, Ritchie GE, Baruah K, Crispin M, Harvey DJ, Singer BB, Lucka L, Wormald MR, Wentworth PJ Jr, Zitzmann N, Rudd PM, Burton DR, Dwek RA. Inhibition of mammalian glycan biosynthesis produces non-self antigens for a broadly neutralising, HIV-1 specific antibody. J. Mol. Biol. (2007) 372(1):16-22
  • Saphire EO, Stanfield RL, Crispin M, Morris G, Zwick MB, Pantophlet RA, Parren PW, Rudd PM, Dwek RA, Burton DR, Wilson IA. Crystal structure of an intact human IgG: antibody asymmetry, flexibility, and a guide for HIV-1 vaccine design. Adv. Exp. Med. Biol. (2003) 535:55-66.

Therapeutic antibodies

  • Baruah K, Bowden TA, Krishna BA, Dwek RA, Crispin M, Scanlan CN. Selective Deactivation of Serum IgG: A General Strategy for the Enhancement of Monoclonal Antibody Receptor Interactions. J Mol Biol. 2012 Apr 5. [Epub ahead of print].
  • Crispin M, Bowden TA, Coles CH, Harlos K, Aricescu AR, Harvey DJ, Stuart DI, Jones EY. Carbohydrate and Domain Architecture of an Immature Antibody Glycoform Exhibiting Enhanced Effector Functions. J. Mol. Biol. (2009) 387(5):1061-6.
  • Harvey DJ, Crispin M, Scanlan C, Singer BB, Lucka L, Chang VT,  Radcliffe CM, Thobhani S, Yuen CT, Rudd PM. Differentiation between isomeric triantennary N-linked glycans by negative ion MS/MS and confirmation of  glycans containing galactose attached to the bisecting (b1-4 GlcNAc) residue in N-glycans from IgG. Rapid Comm. Mass Spectrom. (2008). 22(7):1047-1052.

Glycoprotein engineering and structural biology

  • Goodfellow JJ, Baruah K, Yamamoto K, Bonomelli C, Krishna K, Harvey DJ, Crispin M, Scanlan CN, Davis BG. An endoglycosidase with alternative glycan specificity allows broadened glycoprotein remodelling. J. Am. Chem. Soc. 2012. In press.
  • Yu C, Crispin M, Sonnen AFP, Harvey DJ, Chang VT, Evans EJ, Scanlan CN, Stuart DI, Gilbert RJC and Davis SJ. Use of the a-mannosidase I inhibitor kifunensine allows crystallization of apo CTLA-4 homodimer produced in Chinese hamster ovary cells. Acta Crytstallographica F (2011) 67(Pt 7):785-9.
  • Davis SJ and Crispin M. Solutions to the Glycosylation Problem for Low- and High-Throughput Structural Glycoproteomics. In Functional and Structural Proteomics of Glycoproteins by R. Owens & J. Nettleship (Eds.) 2010. ISBN: 978-90-481-9354-7. 
  • Crispin M, Bowden TA, Scanlan CN. Structure and Biosynthesis of Glycoprotein Carbohydrates. In Comprehensive Biotechnology by M. Butler et al. (Eds) (2011).  
  • Crispin M, Chang VT, Harvey DJ, Dwek RA, Evans EJ, Stuart DI, Jones EY, Lord JM, Spooner RA, Davis SJ. A human embryonic kidney 293T cell line mutated at the Golgi a-mannosidase II locus. J. Biol. Chem. (2009) 284(32):21684-95.
  • Crispin M, Stuart DI, Jones EY. Building meaningful models of glycoproteins. Nat. Struct. Mol. Biol. (2007) 14(5):354.
  • Chang VT, Crispin M, Aricescu AR, Harvey DJ, Nettleship JE, Fennelly JA, Yu C, Boles KS, Evans EJ, Stuart DI, Dwek RA, Jones EY, Owens RJ, Davis SJ. Glycoprotein structural genomics: solving the glycosylation problem. Structure. (2007) 15(3):267-73.
  • Nettleship JE, Aplin R, Radu Aricescu A, Evans EJ, Davis SJ, Crispin M, Owens RJ. Analysis of variable N-glycosylation site occupancy in glycoproteins by liquid chromatography electrospray ionization mass spectrometry.  Anal. Biochem. (2007) 361(1):159-51. 
  • Crispin M, Aricescu AR, Chang VT, Stuart DI, Jones EY, Dwek RA, Davis SJ, Harvey DJ.  Disruption of a-mannosidase processing induces non-canonical hybrid-type glycosylation. FEBS Letters. (2007) 581(10):1963-8.
  • Crispin M, Harvey DJ, Chang VT, Yu C, Aricescu AR, Jones EY, Davis SJ, Dwek RA, Rudd PM. Inhibition of hybrid- and complex-type glycosylation   reveals the presence of the GlcNAc transferase I-independent fucosylation pathway. Glycobiology. (2006) 16(8):748-56.

Structure of emerging viruses

  • Bowden TA, Crispin M, Jones EY, Stuart DI. Shared paramyxoviral glycoprotein architecture is adapted for diverse attachment strategies. Biochem. Soc. Trans. (2010) 38(5):1349-55. 
  • Bowden TA, Crispin M, Harvey DJ, Jones EY, Stuart DI. Dimeric Architecture of the Hendra Virus Attachment Glycoprotein: Evidence for a Conserved Mode of Assembly. J Virol. (2010) Jun;84(12):6208-17.
  • Bowden TA, Crispin M, Graham SC, Harvey DJ, Grimes JM, Jones EY, and Stuart DI. Unusual molecular architecture of the Machupo virus attachment glycoprotein. J. Virol. (2009) 83(16):8259-65.   
  • Bowden TA, Crispin M, Harvey DJ, Aricescu AR, Grimes JM, Jones EY, Stuart DI. Crystal structure and carbohydrate analysis of Nipah virus attachment glycoprotein: a template for antiviral and vaccine design. J. Virol. (2008) 82(23):11628-36.

Molecular immunology

  • Harvey DJ, Crispin M, Moffat BE, Smith SL, Rudd PM, Sim RB. Identification of high-mannose and multiantennary complex-type N-linked glycans containing a-galactose epitopes from nurse shark IgM. Glycoconjugate J. (2009) 26(8):1055-64.
  • Tsiftsoglou SA, Arnold JN, Roversi P, Crispin M, Radcliffe C, Lea SM, Dwek RA, Rudd PM, Sim RB. Human complement factor I glycosylation: structural and functional characterisation of the N-linked oligosaccharides.  Biochim. Biophys. Acta. (2006) 1764(11):1757-66.
  • Giabbai B, Sidobre S, Crispin M, Sanchez-Ruiz Y, Bachi A, Kronenberg M, Wilson IA, Degano M. Crystal structure of mouse CD1d bound to the self ligand phosphatidylcholine: a molecular basis for NKT cell activation. J. Immunol. (2005) 175(2):9777-84.
  • Zajonc DM, Crispin M, Bowden TA, Young DC, Cheng TY, Hu J, Costello CE, Rudd PM, Dwek RA, Miller MJ, Brenner MB, Moody DB, Wilson IA. Molecular mechanism of lipopeptide presentation by CD1a. Immunity. (2005) 22(2):209-19.
  • Arnold JN, Radcliffe CM, Wormald MR, Royle L, Harvey DJ, Crispin M, Dwek RA, Sim RB, Rudd PM. The glycosylation of human serum IgD and IgE and the accessibility of identified oligomannose structures for interaction with mannan-binding lectin. J. Immunol. (2004) 173(11):6831-40.
  • Crispin M, Ritchie GE, Critchley AJ, Morgan BP, Wilson IA, Dwek RA, Sim RB, Rudd PM. Monoglucosylated glycans in the secreted human complement component C3: implications for protein biosynthesis and structure. FEBS Lett. (2004) 566(13):270-4.
  • Lukacik P, Roversi P, White J, Esser D, Smith GP, Billington J, Williams PA, Rudd PM, Wormald MR, Harvey DJ, Crispin M, Radcliffe CM, Dwek RA, Evans DJ, Morgan BP, Smith RA, Lea SM. Complement regulation at the molecular level: the structure of decay-accelerating factor. Proc. Natl Acad. Sci. USA. (2004) 101(5):1279-84.
  • Magnadottir B, Crispin M, Royle L, Colominas C, Harvey DJ, Dwek RA, Rudd PM. The carbohydrate moiety of serum IgM from Atlantic cod (Gadus morhua L.). Fish Shellfish Immunol. (2002) 12(3):2092-7.
  • Saphire EO, Stanfield RL, Crispin M, Parren PW, Rudd PM, Dwek RA, Burton DR, Wilson IA. Contrasting IgG structures reveal extreme asymmetry and flexibility. J. Mol. Biol. (2002) 319(1):99-18.

News:

Latest news from Oriel's active biochemistry community.

Contact:

Dr Max Crispin
Oxford Glycobiology Institute
Department of Biochemistry
University of Oxford
South Parks Road
Oxford OX1 3QU
Lab:  01865 275340
Email: Email: max .crispin @ bioch .ox .ac .uk