Department of Biology & Biochemistry
jean_van_den_elsen

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4 South 0.26A 

Email: bssjmhve@bath.ac.uk

Tel: +44 (0) 1225 383639 

 

Dr Jean van den Elsen

Profile

Current Research

The aim of my research is to study the structural and physico-chemical characteristics of proteins involved in maintaining homeostasis of the human body. I am particularly interested in proteins, and their physiologically relevant complexes, that determine the elemental struggle between pathogenic microbes and the immune system of the host.

The Complement System and Microbial Immune Evasion

The human complement system is comprised of about 20 plasma proteins and 10 receptors on cell membranes. Its primary function is to defend the host against microbial infections, leading to the clearance of antigen-antibody complexes and bacterial lysis. Many bacterial pathogens have evolved ways to adapt to their host environment and survive host immune attack by producing a variety of immune-modulatory factors. My laboratory studies the structural and functional aspects of the interactions between these immune evasion proteins and the complement system. This information will help to design better vaccines and drugs for the treatment of autoimmune diseases.

Protein Glycation

The attachment of sugars to proteins is a very important and well-controlled process in healthy individuals. Sugar-modified proteins (glycoproteins) add to the complexity and diversity of the complement of proteins (proteome) and also control a protein’s location in a cell or the body, its activity, and its interactions with other proteins. Undesired sugar modifications, however, may also occur in the form of glycation, where carbohydrates, such as glucose covalently bind to a protein without the controlling action of an enzyme. The degree of protein glycation has been shown to be an important factor and indicator in ageing and age-related chronic disease states such as diabetes, cardiovascular disease, autoimmune disease, cancer and Alzheimer's disease.

In collaboration with Dr Tony James and Dr Rob Williams we are developing new tools to detect, identify and quantify carbohydrate modifications in glycated proteins that can ultimately be used as diagnostic tools.

Publications

Catici, D. A. M., Amos, H. E., Yang, Y., van den Elsen, J. M. H. and Pudney, C. R., 2016. Forthcoming. The red edge excitation shift phenomenon can be used to unmask protein structural ensembles:implications for NEMO-ubiquitin interactions. FEBS Journal

Mulley, G., Beeton, M. L., Wilkinson, P., Vlisidou, I., Ockendon-Powell, N., Hapeshi, A., Tobias, N. J., Nollmann, F. I., Bode, H. B., Van Den Elsen, J., Ffrench-Constant, R. H. and Waterfield, N. R., 2015. From insect to man:Photorhabdus sheds light on the emergence of human pathogenicity. PLoS ONE, 10 (12), e0144937.

Baraka-Vidot, J., Planesse, C., Meilhac, O., Militello, V., Van Den Elsen, J., Bourdon, E. and Rondeau, P., 2015. Glycation alters ligand binding, enzymatic, and pharmacological properties of human albumin. Biochemistry, 54 (19), pp. 3051-3062.

Laabei, M., Jamieson, W. D., Yang, Y., Van Den Elsen, J. and Jenkins, A. T. A., 2014. Investigating the lytic activity and structural properties of Staphylococcus aureus phenol soluble modulin (PSM) peptide toxins. Biochimica Et Biophysica Acta-Biomembranes, 1838 (12), pp. 3153-3161.

Marrott, N., Marshall, J. J. T., Svergun, D. I., Crennell, S., Hough, D. W., Van Den Elsen, J. and Danson, M., 2014. Why are the 2-oxoacid dehydrogenase complexes so large? Generation of an active trimeric complex. Biochemical Journal, 463 (3), pp. 405-412.

Laabei, M., Recker, M., Rudkin, J. K., Aldeljawi, M., Gulay, Z., Sloan, T. J., Williams, P., Endres, J. L., Bayles, K. W., Fey, P. D., Yajjala, V. K., Widhelm, T., Hawkins, E., Lewis, K., Parfett, S., Scowen, L., Peacock, S. J., Holden, M., Wilson, D., Read, T. D., Van Den Elsen, J., Priest, N. K., Feil, E. J., Hurst, L. D., Josefsson, E. and Massey, R. C., 2014. Predicting the virulence of MRSA from its genome sequence. Genome Research, 24 (5), pp. 839-849.

Pereira Morais, M. P., Marshall, D., Flower, S. E., Caunt, C. J., James, T. D., Williams, R. J., Waterfield, N. R. and Van Den Elsen, J. M. H., 2013. Analysis of protein glycation using fluorescent phenylboronate gel electrophoresis. Scientific Reports, 3, 1437.

Bull, S.D., Davidson, M.G., Van Den Elsen, J.M.H., Fossey, J.S., Jenkins, A.T.A., Jiang, Y.-B., Kubo, Y., Marken, F., Sakurai, K., Zhao, J. and James, T.D., 2013. Exploiting the reversible covalent bonding of boronic acids:Recognition, sensing, and assembly. Accounts of Chemical Research, 46 (2), pp. 312-326.

Priest, N. K., Rudkin, J. K., Feil, E. J., Van Den Elsen, J. M. H., Cheung, A., Peacock, S. J., Laabei, M., Lucks, D. A., Recker, M. and Massey, R. C., 2012. From genotype to phenotype: can systems biology be used to predict Staphylococcus aureus virulence? Nature Reviews Microbiology, 10 (11), pp. 791-797.

Koch, T. K., Reuter, M., Barthel, D., Böhm, S., Van Den Elsen, J., Kraiczy, P., Zipfel, P. F. and Skerka, C., 2012. Staphylococcus aureus Proteins Sbi and Efb Recruit Human Plasmin to Degrade Complement C3 and C3b. PLoS ONE, 7 (10), e47638.

Fossey, J.S., D'Hooge, F., van den Elsen, J.M.H., Pereira Morais, M.P., Pascu, S.I., Bull, S.D., Marken, F., Jenkins, A.T.A., Jiang, Y.-B. and James, T.D., 2012. The development of boronic acids as sensors and separation tools. Chemical Record, 12 (5), pp. 464-478.

Shariki, S., Cox, O.T.L., Tickell, D.A., James, T.D., Dale, S.E.C., Marken, F., Pereira Morais, M.P., Van Den Elsen, J.M.H. and Bending, S., 2012. Coil-by-coil assembly of poly[acrylamide-co-3-(methacryl-amido)- phenylboronic acid] with polydiallyldimethyl-ammonium to give alizarin red S responsive films. Journal of Materials Chemistry, 22 (36), pp. 18999-19006.

Marrott, N. L., Marshall, J. J. T., Svergun, D. I., Crennell, S. J., Hough, D. W., Danson, M. J. and van den Elsen, J. M. H., 2012. The catalytic core of an archaeal 2-oxoacid dehydrogenase multienzyme complex is a 42-mer protein assembly. FEBS Journal, 279 (5), pp. 713-723.

Pereira Morais, M. P., Fossey, J. S., James, T. D. and van den Elsen, J., 2012. Analysis of protein glycation using phenylboronate acrylamide gel electrophoresis. In: Kurien, B. T. and Scofield, R. H., eds. Protein Electrophoresis.869 ed. Springer, pp. 93-109.

D'Hooge, F., Elfeky, S. A., Flower, S., Pascu, S. I., Jenkins, A. T. A., van den Elsen, J., James, T. and Fossey, J., 2012. Biotinylated boronic acid fluorophore conjugates: quencher elimination strategy for imaging and saccharide detection. RSC Advances, 2, pp. 3274-3280.

van den Elsen, J. M. H. and Isenman, D. E., 2011. A crystal structure of the complex between human complement receptor 2 and its ligand C3d. Science, 332 (6029), pp. 608-611.

Clark, E. A., Crennell, S., Upadhyay, A., Zozulya, A. V., Mackay, J. D., Svergun, D. I., Bagby, S. and van den Elsen, J. M. H., 2011. A structural basis for Staphylococcal complement subversion:X-ray structure of the complement-binding domain of Staphylococcus aureus protein Sbi in complex with ligand C3d. Molecular Immunology, 48 (4), pp. 452-462.

Jones, R. T., Bakker, S. E., Stone, D., Shuttleworth, S. N., Bounds, S., McCart, C., Daborn, P. J., Ffrench-Constant, R. H. and van den Elsen, J. M. H., 2010. Homology modelling of Drosophila cytochrome P450 enzymes associated with insecticide resistance. Pest Management Science, 66 (10), pp. 1106-1115.

Isenman, D. E., Leung, E., Mackay, J. D., Bagby, S. and van den Elsen, J. M. H., 2010. Mutational analyses reveal that the staphylococcal immune evasion molecule Sbi and complement receptor 2 (CR2) share overlapping contact residues on C3d: implications for the controversy regarding the CR2/C3d cocrystal structure. The Journal of Immunology, 184 (4), pp. 1946-1955.

Pereira Morais, M. P., Mackay, J. D., Bhamra, S. K., Buchanan, J. G., James, T. D., Fossey, J. S. and van den Elsen, J. M. H., 2010. Analysis of protein glycation using phenylboronate acrylamide gel electrophoresis. Proteomics, 10 (1), pp. 48-58.

Meierhofer, T., van den Elsen, J. M. H., Cameron, P. J., Munoz-Berbel, X. and Jenkins, A. T. A., 2010. The interaction of serum albumin with cholesterol containing lipid vesicles. Journal of Fluorescence, 20 (1), pp. 371-376.

Ma, W. M. J., Pereira Morais, M. P., D'Hooge, F., van den Elsen, J. M. H., Cox, J. P. L., James, T. D. and Fossey, J. S., 2009. Dye displacement assay for saccharide detection with boronate hydrogels. Chemical Communications, 2009 (5), pp. 532-534.

Elfeky, S. A., D'Hooge, F., Poncel, L., Chen, W. B., Perera, S. P., van den Elsen, J. M. H., James, T. D., Jenkins, A. T. A., Cameron, P. J. and Fossey, J. S., 2009. A surface plasmon enhanced fluorescence sensor platform. New Journal of Chemistry, 33 (7), pp. 1466-1469.

Clark, E., Upadhyay, A., Bagby, S. and van den Elsen, J., 2009. IsaB, a new immunoglobulin-binding protein from Staphylococcus aureus. Molecular Immunology, 46 (14), pp. 2834-2835.

Isenman, D. E., Leung, E., Mackay, J. D., Bagby, S. and van den Elsen, J. M. H., 2008. Mutational analyses reveal that the staphylococcal immune evasion molecule Sbi and complement eeceptor 2 (CR2) share overlapping contact residues on C3d: Implications for the controversy regarding the CR2/C3d cocrystal structure. Molecular Immunology, 45 (16), pp. 4095-4096.

Upadhyay, A., Burman, J. D., Clark, E. A., Leung, E., Isenman, D. E., van den Elsen, J. M. H. and Bagby, S., 2008. Structure-function analysis of the C3 binding region of Staphylococcus aureus immune subversion protein Sbi. Journal of Biological Chemistry, 283 (32), pp. 22113-22120.

D'Hooge, F., Rogalle, D., Thatcher, M. J., Perera, S., van den Elsen, J. M. H., Jenkins, T. A., James, T. and Fossey, J., 2008. Polymerisation resistant synthesis of methacrylamido phenylboronic acids. Polymer, 49 (16), pp. 3362-3365.

Burman, J. D., Leung, E., Atkins, K. L., O'Seaghdha, M. N., Lango, L., Bernado, P., Bagby, S., Svergun, D. I., Foster, T. J., Isenman, D. E. and van den Elsen, J. M. H., 2008. Interaction of human complement with Sbi, a staphylococcal immunoglobulin-binding protein: indications of a novel mechanism of complement evasion by Staphylococcus aureus. Journal of Biological Chemistry, 283 (25), pp. 17579-17593.

Upadhyay, A., Wu, H.-L., Williams, C., Field, T., Galyov, E. E., van den Elsen, J. M. H. and Bagby, S., 2008. The guanine-nucleotide-exchange factor BopE from Burkholderia pseudomallei adopts a compact version of the Salmonella SopE/SopE2 fold and undergoes a closed-to-open conformational change upon interaction with Cdc42. Biochemical Journal, 411 (3), pp. 485-493.

Atkins, K. L., Burman, J. D., Chamberlain, E. S., Cooper, J. E., Poutrel, B., Bagby, S., Jenkins, T. A., Feil, E. J. and van den Elsen, J. M. H., 2008. S. aureus IgG-binding proteins SpA and Sbi: host specificity and mechanisms of immune complex formation. Molecular Immunology, 45 (6), pp. 1600-1611.

Jackson, T. R., Springall, J. S., Rogalle, D., Masurnoto, N., Li, H. C., D'Hooge, F., Perera, S. P., Jenkins, A. T. A., James, T. D., Fossey, J. S. and van den Elsen, J. M. H., 2008. Boronate affinity saccharide electrophoresis:A novel carbohydrate analysis tool. Electrophoresis, 29 (20), pp. 4185-4191.

van den Elsen, J., Upadhyay, A., Burman, J., Leung, E., Clark, E., Isenman, D. and Bagby, S., 2008. Structure–function analysis of the novel Staphylococcus aureus immune subversion protein Sbi. Molecular Immunology, 45 (16), p. 4119.

Haupt, K., Reuter, M., van den Elsen, J. M. H., Burman, J., Halbich, S., Richter, J., Skerka, C. and Zipfel, P. F., 2008. The Staphylococcus aureus Protein Sbi Acts as a Complement Inhibitor and Forms a Tripartite Complex with Host Complement Factor H and C3b. PLoS Pathogens, 4 (12), e1000250.

This list was generated on Mon Jul 25 02:55:04 2016 IST.

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