Morby, Andrew - Cardiff University - School of Biosciences

研究领域

Transition Metals and Microbes Transition-metal ions present an interesting chemical paradox to living cells. Whilst these cations have significant toxicity and can act as potent disrupters of biological systems, a wide spectrum, however, are also essential (micro-) nutrients, since they play important roles in many biochemical processes, either by facilitating redox reactions or by stabilising chemical / protein structure. An improved understanding of metal-ion metabolism is crucial given the fundamental importance of metal-ions chemistry in the cell (e.g. the generation of reactive oxygen species, electron transport, ribosomal function, transcription, replication). Increasingly, many metabolic disorders (e.g diabetes, hereditary haemochromatosis, Menkes' disease and Wilson's disease) and neurodegenerative diseases (e.g. Alzheimers, Creutzfeld-Jacob), are thought to result from aberrant metal-ion metabolism. A fundamental aspect of metal-ion metabolism that remains relatively uncharacterised is the context and number of metal-ions within cells. To date there is little data detailing the proteins/nucleic acids/metabolites that bind metal-ions within the cell and how their association with cellular components impacts their biological availability and activity. Cyclic di-Guanosine Monophosphate (c-di-GMP) Cyclic-di guanosine monophosphate (c-di-GMP) has been implicated in the regulation of exo-polysaccharide production and the the switch between sessility and motility in bacteria. The current dogma is that the production of this signalling molecule is controlled by the GGDEF domain protein, e.g. PleD (Hecht & Newton, 1995; Aldridge et al., 2003). The GGDEF domain, is both widespread and numerous in prokaryotes and has been shown to have a diguanylate cyclase (DGC) activity, with a role in the production of c-di-GMP from GTP (Tal et al 1998). The majority of bacterial genomes harbour multiple genes that appear to encode GGDEF-domain proteins in addition to the "opposing" EAL domain proteins that have been shown to degrade c-di-GMP (phosphodiesterase (PDE) indeed Vibrio vulnificus has up to 59 such examples. What was first identified as an allosteric regulator of cellulose synthesis is now thought to represent a key second messenger in an elaborate and universal bacterial post-translational regulation system (Reviewed in Jenal 2004, D'Argenio and Miller, 2004;Romling et al., 2005). The opposing cycles of c-di-GMP generation and degradation form the basis of a multi-input signal transduction system that has a global effect on bacterial behaviour, fitness and adaptation to the enviroment. We are seeking to understand the action of this network in E.coli by the use of a range of molecular and genomic approaches. Outstanding questions include , what are the input signals to these catalytic centres?, what are the outputs (e,g, cellulose synthesis)?, what roles do the many GGDEF and EAL proteins play in the cell?

近期论文

查看导师新发文章（温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Blencowe, D., al Jubori, S. and Morby, A. P. 2011. Identification of a novel function for the FtsL cell division protein from Escherichia coli K12. Biochemical and Biophysical Research Communications 411(1), pp. 44-49. (10.1016/j.bbrc.2011.06.083) Brown, R. C., Marchesi, J. R. and Morby, A. P. 2011. Functional characterisation of Lp_2714, an EAL-domain protein from Lactobacillus plantarum. Biochemical and Biophysical Research Communications 411(1), pp. 132-136. (10.1016/j.bbrc.2011.06.112) Allen, M. J., White, G. F. and Morby, A. P. 2006. The response of Escherichia coli to exposure to the biocide polyhexamethylene biguanide. Microbiology 152(4), pp. 989-1000. (10.1099/mic.0.28643-0) Gul, S.et al. 2004. Staphylococcus aureus DNA ligase: characterization of its kinetics of catalysis and development of a high-throughput screening compatible chemiluminescent hybridization protection assay. Biochemical Journal 383(3), pp. 551-559. (10.1042/BJ20040054) Allen, M. J., Morby, A. P. and White, G. F. 2004. Cooperativity in the binding of the cationic biocide polyhexamethylene biguanide to nucleic acids. Biochemical and Biophysical Research Communications 318(2), pp. 397-404. (10.1016/j.bbrc.2004.04.043) Blencowe, D. K. and Morby, A. P. 2003. Zn(II) metabolism in prokaryotes. FEMS Microbiology Reviews 27(2-3), pp. 291-311. (10.1016/S0168-6445(03)00041-X) Brown, N. L., Morby, A. P. and Robinson, N. J. 2003. Guest Editorial. FEMS Microbiology Reviews 27(2-3), pp. 129. (10.1016/S0168-6445(03)00040-8) Brocklehurst, K. R., Megit, S. J. and Morby, A. P. 2003. Characterisation of CadR from Pseudomonas aeruginosa: a Cd(II)-responsive MerR homologue. Biochemical and Biophysical Research Communications 308(2), pp. 234-239. (10.1016/S0006-291X(03)01366-4) Khan, S.et al. 2002. The functional analysis of directed amino-acid alterations in ZntR from Escherichia coli. Biochemical and Biophysical Research Communications 299(3), pp. 438-445. (10.1016/S0006-291X(02)02660-8) Wilson, J.et al. 2000. MerF is a mercury transport protein: different structures but a common mechanism for mercuric ion transporters?. FEBS Letters 472(1), pp. 78-82. (10.1016/S0014-5793(00)01430-7)