Research areas
We are using molecular, cellular and structural biology to understand the structure and function of proteins involved in pathogenesis with a view to developing new drugs against a range of disease caused by microorganisms. The sialidase (or neuraminidase) superfamily are virulence factors in influenza, parainfluenza, cholera and pneumonia. Our structural studies on the paramyxovirus hemagglutinin-neuraminidase (HN) has led to the structure-based development of a new drug that is a potential treatment for childhood parainfleunza. We are currently studying the sialidases from Streptococcus pneumoniae and Pseudomonas aeruginosa, and developing inhibitors against these enzymes that are key virulence facotrs in the respiratory diseases caused by these bacteria.
More recently, we have engineered mutlivalent forms of a couple of carbohydrate-binding modules specific for sialic acid, a key component of the receptor used by the influenza virus, parainfluenza virus, some coronaviruses and pneumococci. Experients in mice using lethal viral challenges show that these mutlivalent bioloigcs have great potential as a prophylactic for the prevention of certain respiratory diseases.
Selected publications
-
Open access
Development of a structural epitope mimic: an idiotypic approach to HCV vaccine design
Cowton, V. M., Owsianka, A. M., Fadda, V., Ortega-Prieto, A. M., Cole, S. J., Potter, J. A., Skelton, J. K., Jeffrey, N., Di Lorenzo, C., Dorner, M., Taylor, G. L. & Patel, A. H., 8 Jan 2021, In: npj Vaccines. 6, 10 p., 7.Research output: Contribution to journal › Article › peer-review
-
Open access
Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus
Owen, C. D., Tailford, L. E., Monaco, S., Šuligoj, T., Vaux, L., Lallement, R., Khedri, Z., Yu, H., Lecointe, K., Walshaw, J., Tribolo, S., Horrex, M., Bell, A., Chen, X., Taylor, G. L., Varki, A., Angulo, J. & Juge, N., 19 Dec 2017, In: Nature Communications. 8, p. 1-15 15 p., 2196.Research output: Contribution to journal › Article › peer-review
-
Open access
PRIMA-1Met suppresses colorectal cancer independent of p53 by targeting MEK
Lu, T., Zou, Y., Xu, G., Potter, J. A., Taylor, G. L., Duan, Q., Yang, Q., Xiong, H., Qiu, H., Ye, D., Zhang, P., Yu, S., Yuan, X., Zhu, F., Wang, Y. & Xiong, H., 27 Oct 2016, In: Oncotarget. 7, 50, p. 83017-83030 14 p.Research output: Contribution to journal › Article › peer-review
-
Open access
Streptococcus pneumoniae NanC. Structural insights into the specificity and mechanism of a sialidase that produces a sialidase inhibitor
Owen, C. D., Lukacik, P., Potter, J. A., Sleator, O., Taylor, G. L. & Walsh, M. A., 13 Nov 2015, In: Journal of Biological Chemistry. 290, 46, p. 27736-27748 13 p.Research output: Contribution to journal › Article › peer-review
-
Open access
Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation
Tailford, L. E., Owen, C. D., Walshaw, J., Crost, E. H., Hardy-Goddard, J., Le Gall, G., de Vos, W. M., Taylor, G. L. & Juge, N., 8 Jul 2015, In: Nature Communications. 6, 12 p., 7624.Research output: Contribution to journal › Article › peer-review
-
Immunomodulatory Compounds
Taylor, G. L. & Connaris, H., 30 Jul 2015, IPC No. A61K31/74, Patent No. WO2015110831 (A1)Research output: Patent
-
Open access
Sialic acid-binding protein Sp2CBMTD protects mice against lethal challenge with emerging influenza A (H7N9) virus
Govorkova, E. A., Baranovich, T., Marathe, B. M., Yang, L., Taylor, M. A., Webster, R. G., Taylor, G. L. & Connaris, H., Mar 2015, In: Antimicrobial Agents and Chemotherapy. 59, 3, p. 1495-1504 10 p.Research output: Contribution to journal › Article › peer-review
-
Open access
Structural characterization of the carbohydrate-binding module of NanA sialidase, a pneumococcal virulence factor
Yang, L., Connaris, H., Potter, J. A. & Taylor, G. L., 20 Aug 2015, In: BMC Structural Biology. 15, 10 p., 15.Research output: Contribution to journal › Article › peer-review
-
Prevention of influenza by targeting host receptors using engineered proteins
Connaris, H., Govorkova, E. A., Ligertwood, Y., Dutia, B. M., Yang, L., Tauber, S., Taylor, M. A., Alias, N., Hagan, R., Nash, A. A., Webster, R. G. & Taylor, G. L., 29 Apr 2014, In: Proceedings of the National Academy of Sciences of the United States of America. 111, 17, p. 6401-6406Research output: Contribution to journal › Article › peer-review
-
Kinetic and structural evaluation of selected active site mutants of the Aspergillus fumigatus KDNase (sialidase)
Yeung, J. H. F., Telford, J. C., Shidmoossavee, F. S., Bennet, A. J., Taylor, G. L. & Moore, M. M., 23 Dec 2013, In: Biochemistry. 52, 51, p. 9177-86 10 p.Research output: Contribution to journal › Article › peer-review