Background

Qualifications

BSc (Hons) University of Warwick, 1993
MSc University of Newcastle-upon-Tyne, 1994
PhD University of Newcastle-upon-Tyne, 1999

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Research

Research Interests

Our resident gut microbiota, composed of trillions mainly bacterial cells, have co-evolved with us and play an essential role in maintaining normal health and nutrition. Bacterial survival in the gut is dependent on the ability of members of this community to sense and respond rapidly to changes in their dynamic nutrient environment. The major nutrient source for microbes in the distal intestine are plant- and animal-derived polysaccharides from our diets, as the human genome does not encode the enzymes necessary to degrade many of these complex macromolecules.

In my lab we use a range of biochemical, microbiology, genetic and structural techniques to study the molecular mechanisms utilised by our resident gut bacteria to recognise, acquire and degrade complex glycans. The results of this research have applications in a number of areas including the development of biofuels derived from plant cell wall material and in personalised nutrition approaches to optimise microbiota function for the benefit of human health.

Publications

• Bolam DN, van den Berg B. TonB-dependent transport by the gut microbiota: novel aspects of an old problem. Current Opinion in Structural Biology 2018, 51, 35-43.
• Cartmell A, Lowe EC, Baslé A, Firbank SJ, Ndeh DA, Murray H, Terrapon N, Lombard V, Henrissat B, Turnbull JE, Czjzek M, Gilbert HJ, Bolam DN. How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans. Proceedings of the National Academy of Sciences of the United States 2017, 114(27), 7037-7042.
• Glenwright AJ, Pothula KR, Bhamidimarri SP, Chorev DS, Baslé A, Firbank SJ, Zheng H, Robinson CV, Winterhalter M, Kleinekathöfer U, Bolam DN, van den Berg B. Structural basis for nutrient acquisition by dominant members of the human gut microbiota. Nature 2017, Epub ahead of print.
• Rogowski A, Briggs JA, Mortimer JC, Tryfona T, Terrapon N, Lowe EC, Baslé A, Morland C, Day AM, Zheng H, Rogers TE, Thompson P, Hawkins AR, Yadav MP, Henrissat B, Martens EC, Dupree P, Gilbert HJ, Bolam DN. Glycan complexity dictates microbial resource allocation in the large intestine. Nature Communications 2015, 6, 7481.
• Rogowski A, Basle A, Farinas CS, Solovyova A, Mortimer JC, Dupree P, Gilbert HJ, Bolam DN. Evidence That GH115 alpha-Glucuronidase Activity, Which Is Required to Degrade Plant Biomass, Is Dependent on Conformational Flexibility. Journal of Biological Chemistry 2014, 289(1), 53-64.
• Raghavan V, Lowe EC, Townsend GE, Bolam DN, Groisman EA. Tuning transcription of nutrient utilization genes to catabolic rate promotes growth in a gut bacterium. Molecular Microbiology 2014, 93(5), 1010-1025.
• Kovacs K, Willson BJ, Schwarz K, Heap JT, Jackson A, Bolam DN, Winzer K, Minton NP. Secretion and assembly of functional mini-cellulosomes from synthetic chromosomal operons in Clostridium acetobutylicum ATCC 824. Biotechnology for Biofuels 2013, 6, 117.
• Bolam DN, Koropatkin NM. Glycan recognition by the Bacteroidetes Sus-like systems. Current Opinion in Structural Biology 2012, 22(5), 563-569.
• Lowe EC, Baslé A, Czjzek M, Firbank SJ, Bolam DN. A scissor blade-like closing mechanism implicated in transmembrane signaling in a Bacteroides hybrid two-component system. Proceedings of the National Academy of Sciences 2012, 109(19), 7298-7303.
• Nakjang S, Ndeh DA, Wipat A, Bolam DN, Hirt RP. A Novel Extracellular Metallopeptidase Domain Shared by Animal Host-Associated Mutualistic and Pathogenic Microbes. PLoS One 2012, 7(1), 1-18.
• Martens EC, Lowe EC, Chiang H, Pudlo NA, Wu M, McNulty NP, Abbott DW, Henrissat B, Gilbert HJ, Bolam DN, Gordon JI. Recognition and degradation of plant cell wall polysaccharides by two human gut symbionts. PLoS Biology 2011, 9(12), e1001221.
• Bolam DN, Sonnenburg JS. Mechanistic insight into polysaccharide use within the intestinal microbiota. Gut Microbes 2011, 2(2), 86-90.
• Sonnenburg ED, Zheng HJ, Joglekar P, Higginbottom SK, Firbank SJ, Bolam DN, Sonnenburg JL. Specificity of Polysaccharide Use in Intestinal Bacteroides Species Determines Diet-Induced Microbiota Alterations. Cell 2010, 141(7), 1241-1252.
• Montanier C, Flint JE, Bolam DN, Xie HF, Liu ZY, Rogowski A, Weiner DP, Ratnaparkhe S, Nurizzo D, Roberts SM, Turkenburg JP, Davies GJ, Gilbert HJ. Circular Permutation Provides an Evolutionary Link between Two Families of Calcium-dependent Carbohydrate Binding Modules. Journal of Biological Chemistry 2010, 285(41), 31742-31754.
• Montanier C, Money VA, Pires VMR, Flint JE, Pinheiro BA, Goyal A, Prates JAM, Izumi A, Stålbrand H, Morland C, Cartmell A, Kolenova K, Topakas E, Dodson EJ, Bolam DN, Davies GJ, Fontes CMGA, Gilbert HJ. The Active Site of a Carbohydrate Esterase Displays Divergent Catalytic and Noncatalytic Binding Functions. PLoS Biology 2009, 7(3), e1000071.
• Bolam DN, Roberts S, Proctor MR, Turkenburg J, Dodson E, Martinez-Fleites C, Yang M, Davis B, Davies G, Gilbert HJ. The crystal structure of two macrolide glycosyltransferases provides a blueprint for host cell antibiotic immunity. Proceedings of the National Academy of Sciences of the United States of America 2007, 104(13), 5336-5341.
• McCartney L, Blake A, Flint JE, Bolam DN, Boraston A, Gilbert HJ, Knox J. Differential recognition of plant cell walls by microbial xylan-specific carbohydrate-binding modules. Proceedings of the National Academy of Sciences of the United States of America 2006, 103(12), 4765-4770.
• Henshaw J, Horne-Bitschy A, Van Bueren A, Money V, Bolam DN, Czjzek M, Ekborg N, Weiner R, Hutcheson S, Davies G, Boraston A, Gilbert HJ. Family 6 carbohydrate binding modules in β-agarases display exquisite selectivity for the non-reducing termini of agarose chains. Journal of Biological Chemistry 2006, 281(25), 17099-17107.
• Martinez-Fleites C, Proctor MR, Roberts S, Bolam DN, Gilbert HJ, Davies G. Insights into the Synthesis of Lipopolysaccharide and Antibiotics through the Structures of Two Retaining Glycosyltransferases from Family GT4. Chemistry and Biology 2006, 13(11), 1143-1152.
• Blake A, McCartney L, Flint JP, Bolam DN, Boraston A, Gilbert HJ, Knox J. Understanding the biological rationale for the diversity of cellulose-directed carbohydrate-binding modules in prokaryotic enzymes. Journal of Biological Chemistry 2006, 281(39), 29321-29329.
• Najmudin S, Guerreiro C, Carvalho A, Prates J, Correia M, Alves V, Ferreira L, Romão M, Gilbert HJ, Bolam DN, Fontes C. Xyloglucan is recognized by carbohydrate-binding modules that interact with β-glucan chains. Journal of Biological Chemistry 2006, 281(13), 8815-8828.
• Yang M, Proctor M, Bolam DN, Errey J, Field R, Gilbert HJ, Davis B. Probing the breadth of macrolide glycosyltransferases: In vitro remodeling of a polyketide antibiotic creates active bacterial uptake and enhances potency. Journal of the American Chemical Society 2005, 127(26), 9336-9337.
• Flint JE, Bolam DN, Nurizzo D, Taylor EJ, Williamson M, Walters C, Davies G, Gilbert HJ. Probing the mechanism of ligand recognition in family 29 carbohydrate-binding modules. Journal of Biological Chemistry 2005, 280(25), 23718-23726.
• Flint J, Taylor E, Yang M, Bolam DN, Tailford L, Martinez-Fleites C, Dodson E, Davis B, Gilbert HJ, Davies G. Structural dissection and high-throughput screening of mannosylglycerate synthase. Nature Structural and Molecular Biology 2005, 12(7), 608-614.
• Tunnicliffe R, Bolam DN, Pell G, Gilbert HJ, Williamson M. Structure of a mannan-specific family 35 carbohydrate-binding module: Evidence for significant conformational changes upon ligand binding. Journal of Molecular Biology 2005, 347(2), 287-296.
• Boraston A, Bolam DN, Gilbert HJ, Davies G. Carbohydrate-binding modules: Fine-tuning polysaccharide recognition. Biochemical Journal 2004, 382(3), 769-781.
• McCartney L, Gilbert HJ, Bolam DN, Boraston A, Knox J. Glycoside hydrolase carbohydrate-binding modules as molecular probes for the analysis of plant cell wall polymers. Analytical Biochemistry 2004, 326(1), 49-54.
• Flint JE, Nurizzo D, Harding S, Longman E, Davies G, Gilbert HJ, Bolam DN. Ligand-mediated dimerization of a carbohydrate-binding module reveals a novel mechanism for protein-carbohydrate recognition. Journal of Molecular Biology 2004, 337(2), 417-426.
• Pires V, Henshaw J, Prates J, Bolam DN, Ferreira L, Fontes C, Henrissat B, Planas A, Gilbert HJ, Czjzek M. The crystal structure of the family 6 carbohydrate binding module from Cellvibrio mixtus endoglucanase 5A in complex with oligosaccharides reveals two distinct binding sites with different ligand specificities. Journal of Biological Chemistry 2004, 279(20), 21560-21568.
• Carvalho A, Goyal A, Prates J, Bolam DN, Gilbert HJ, Pires V, Ferreira L, Planas A, Romão M, Fontes C. The family 11 carbohydrate-binding module of Clostridium thermocellum Lic26A-Cel5E accommodates β-1,4- and β-1,3-1,4-mixed linked glucans at a single binding site. Journal of Biological Chemistry 2004, 279(33), 34785-34793.
• Henshaw J, Bolam DN, Pires V, Czjzek M, Henrissat B, Ferreira L, Fontes C, Gilbert HJ. The family 6 carbohydrate binding module CmCBM6-2 contains two ligand-binding sites with distinct specificities. Journal of Biological Chemistry 2004, 279(20), 21552-21559.
• Bolam DN, Xie H, Pell G, Hogg D, Galbraith G, Henrissat B, Gilbert HJ. X4 modules represent a new family of carbohydrate-binding modules that display novel properties. Journal of Biological Chemistry 2004, 279(22), 22953-22963.
• Pell G, Williamson M, Walters C, Du H, Gilbert HJ, Bolam DN. Importance of hydrophobic and polar residues in ligand binding in the family 15 carbohydrate-binding module from Cellvibrio japonicus Xyn10C. Biochemistry 2003, 42(31), 9316-9323.
• Nagy T, Nurizzo D, Davies G, Biely P, Lakey JH, Bolam DN, Gilbert HJ. The α-Glucuronidase, GlcA67A, of Cellvibrio japonicus utilizes the carboxylate and methyl groups of aldobiouronic acid as important substrate recognition determinants. Journal of Biological Chemistry 2003, 278(22), 20286-20292.
• Abou-Hachem M, Karlsson EN, Simpson PJ, Linse S, Sellers P, Williamson MP, Jamieson SJ, Gilbert HJ, Bolam DN, Holst O. Calcium binding and thermostability of carbohydrate binding module CBM4-2 of Xyn10A from Rhodothermus marinus. Biochemistry 2002, 41(18), 5720-5729.
• Charnock S, Bolam DN, Nurizzo D, Szabó L, McKie V, Gilbert HJ, Davies G. Promiscuity in ligand-binding: The three-dimensional structure of a Piromyces carbohydrate-binding module, CBM29-2, in complex with cello-and mannohexaose. Proceedings of the National Academy of Sciences of the United States of America 2002, 99(22), 14077-14082.
• Freelove ACJ, Bolam DN, White P, Hazlewood GP, Gilbert HJ. A Novel Carbohydrate-binding Protein Is a Component of the Plant Cell Wall-degrading Complex of Piromyces equi. Journal of Biological Chemistry 2001, 276(46), 43010-43017.
• Xie H, Gilbert HJ, Charnock S, Davies G, Williamson M, Simpson P, Raghothama S, Fontes C, Dias F, Ferreira L, Bolam DN. Clostridium thermocellum Xyn10B carbohydrate-binding module 22-2: The role of conserved amino acids in ligand binding. Biochemistry 2001, 40(31), 9167-9176.
• Hogg D, Woo E, Bolam D, McKie V, Gilbert H, Pickersgill R. Crystal Structure of Mannanase 26A from Pseudomonas cellulosa and Analysis of Residues Involved in Substrate Binding. Journal of Biological Chemistry 2001, 276(33), 31186-31192.
• Bolam DN, Xie H, White P, Simpson P, Hancock S, Williamson M, Gilbert HJ. Evidence for synergy between family 2b carbohydrate binding modules in Cellulomonas fimi Xylanase 11A. Biochemistry 2001, 40(8), 2468-2477.
• Xie H, Bolam DN, Nagy T, Szabó L, Cooper A, Simpson P, Lakey J, Williamson M, Gilbert H. Role of hydrogen bonding in the interaction between a xylan binding module and xylan. Biochemistry 2001, 40(19), 5700-5707.
• Szabó L, Jamal S, Xie H, Charnock SJ, Bolam DN, Gilbert HJ, Davies GJ. Structure of a Family 15 Carbohydrate-binding Module in Complex with Xylopentaose. Journal of Biological Chemistry 2001, 276(52), 49061-49065.
• Szabó L, Jamal S, Xie H, Charnock S, Bolam DN, Gilbert HJ, Davies G. Structure of a family 15 carbohydrate-binding module in complex with xylopentaose: Evidence that xylan binds in an approximate 3-fold helical conformation. Journal of Biological Chemistry 2001, 276(52), 49061-49065.
• Czjzek M, Bolam DN, Mosbah A, Allouch J, Fontes C, Ferreira L, Bornet O, Zamboni V, Darbon H, Smith N, Black G, Henrissat B, Gilbert HJ. The Location of the Ligand-binding Site of Carbohydrate-binding Modules That Have Evolved from a Common Sequence Is Not Conserved. Journal of Biological Chemistry 2001, 276(51), 48580-48587.
• Simpson P, Xie H, Bolam DN, Gilbert HJ, Williamson M. The structural basis for the ligand specificity of family 2 carbohydrate-binding modules. Journal of Biological Chemistry 2000, 275(52), 41137-41142.
• Charnock S, Bolam DN, Turkenburg J, Gilbert HJ, Ferreira L, Davies G, Fontes C. The X6 'thermostabilizing' domains of xylanases are carbohydrate-binding modules: Structure and biochemistry of the Clostridium thermocellum X6b domain. Biochemistry 2000, 39(17), 5013-5021.
• Busse-Wicher M, Gomes TCF, Tryfona T, Nikolovski N, Stott K, Grantham NJ, Bolam DN, Skaf MS, Dupree P. The pattern of xylan acetylation suggests xylan may interact with cellulose microfibrils as a twofold helical screw in the secondary plant cell wall of Arabidopsis thaliana. Plant Journal 2014, 79(3), 492-506.
• Bolam DN, van den Berg B, Glenwright AJ. Structural basis for glycan acquisition by dominant members of the human gut microbiota. In: 2016 Annual Meeting of the Society for Glycobiology. 2016, New Orleans, Louisiana: Oxford University Press.
• Guo B-S, Zheng F, Crouch L, Cai Z-P, Wang M, Bolam DN, Liu L, Voglmeir J. Cloning, purification and biochemical characterisation of a GH35 beta-1,3/beta-1,6-galactosidase from the mucin-degrading gut bacterium Akkermansia muciniphila. Glycoconjugate Journal 2018, 32(3), 255-263.
• Joglekar P, Sonnenburg ED, Higginbottom SK, Earle KA, Morland C, Shapiro-Ward S, Bolam DN, Sonnenburg JL. Genetic variation of the SusC/SusD homologs from a polysaccharide utilization locus underlies divergent fructan specificities and functional adaptation in Bacteroides thetaiotaomicron strains. mSphere 2018, 3(3).