个人简介
My research career has focused on the gram positive bacterium Bacillus subtilis. During my PhD I purified and characterised the replication terminator protein (RTP) and its DNA binding sites (Lewis et al., J. Bacteriol 171, 3564-3567 (1989); Lewis et al., J. Mol. Biol. 214, 73-84 (1990)). These sites are regions of DNA where oppositely moving replication forks meet and newly replicated chromosomes are resolved prior to segregation. During my post-doctoral research I was responsible for the development of cell biological techniques and vectors for visualising gene expression and protein localisation in live bacterial cells (Lewis et al., PNAS 91, 3849-3853 (1994); Lewis et al., Mol Microbiol 13, 655-662 (1994); Lewis and Errington, Microbiology 142, 733-740 (1996); Lewis and Marston, Gene 227, 101-109 (1999); Feucht and Lewis, Gene 264, 289-297 (2001)).
These techniques have been widely adopted by research groups involved in microbial cell biology, and the plasmid vectors have now been distributed directly to well over 100 laboratories world-wide, although they are now also distributed by the Bacillus Genetic Stock Centre. These techniques were instrumental in determining the establishment of compartment specificity of developmentally regulated s-factors during sporulation in B. subtilis (Lewis et al., PNAS 91, 3849-3853 (1994)). I also showed that prespore specific accumulation of the transcription regulator SpoIIAA was responsible for initiation of compartment-specific gene expression during development, that this accumulation was probably due to prespore-specific activity of the phosphatase SpoIIE, and that a programme of proteolysis was initiated following this activation event (Lewis et al., Genes Cell 1, 881-894 (1996); Lewis et al., J. Bacteriol 180, 3276-3284 (1998)). I was also involved in work that showed that the highly conserved SpoIIIE (FtsK) protein is a DNA translocase that moves DNA through a division septum (Wu et al., Genes Dev 9, 1316-1326 (1995)). This was the first example of such a phenomenon, and was a very significant finding as previously it was assumed that DNA was segregated into daughter cells/different compartments prior to division septum formation. Finally, I have shown that transcription and translation are spatially separated within bacteria (Lewis et al., EMBO J 19, 710-718 (2000)). This was an unexpected result as the 2 processes were thought to be very tightly coupled in bacteria. Furthermore, transcription becomes concentrated into a sub-fraction of the bacterial nucleoid at higher growth rates. These transcription foci have been shown to be the sites of rRNA synthesis, and my laboratory is now focussing on characterising transcription complexes and their structure in detail.
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2016 Ma C, Yang X, Lewis PJ, 'Bacterial Transcription as a Target for Antibacterial Drug Development.', Microbiol Mol Biol Rev, 80 139-160 (2016)
2016 Thach O, Mielczarek M, Ma C, Kutty SK, Yang X, Black DS, et al., 'From indole to pyrrole, furan, thiophene and pyridine: Search for novel small molecule inhibitors of bacterial transcription initiation complex formation.', Bioorg Med Chem, 24 1171-1182 (2016)
2016 Ma C, Yang X, Lewis PJ, 'Bacterial Transcription Inhibitor of RNA Polymerase Holoenzyme Formation by Structure-Based Drug Design: From in Silico Screening to Validation', ACS Infectious Diseases, 2 39-46 (2016) [C1]
2015 American Chemical Society.Bacterial transcription is a proven target for antibacterial research. However, most of the known inhibitors targeting transcription are from nat... [more]
2015 Mielczarek M, Thomas RV, Ma C, Kandemir H, Yang X, Bhadbhade M, et al., 'Synthesis and biological activity of novel mono-indole and mono-benzofuran inhibitors of bacterial transcription initiation complex formation', Bioorganic and Medicinal Chemistry, (2015) [C1]
Our ongoing research focused on targeting transcription initiation in bacteria has resulted in synthesis of several classes of mono-indole and mono-benzofuran inhibitors that targ... [more]
2015 Yin Z, Whittell LR, Wang Y, Jergic S, Ma C, Lewis PJ, et al., 'Bacterial Sliding Clamp Inhibitors that Mimic the Sequential Binding Mechanism of Endogenous Linear Motifs.', J Med Chem, 58 4693-4702 (2015) [C1]
2015 Bi Y, Yang X, Zhang T, Liu Z, Zhang X, Lu J, et al., 'Design, synthesis, nitric oxide release and antibacterial evaluation of novel nitrated ocotillol-type derivatives', European Journal of Medicinal Chemistry, 101 71-80 (2015) [C1]
2015 Elsevier Masson SAS.Abstract Nitric oxide (NO) and its auto-oxidation products are known to disrupt normal bacterial function and NO releasing molecules have the potential... [more]
2015 Ma C, Mobli M, Yang X, Keller AN, King GF, Lewis PJ, 'RNA polymerase-induced remodelling of NusA produces a pause enhancement complex.', Nucleic acids research, 43 2829-2840 (2015) [C1]
2015 Yang X, Ma C, Lewis PJ, 'Identification of inhibitors of bacterial RNA polymerase', Methods, 86 45-50 (2015) [C1]
2015.Very few clinically available antibiotics target bacterial RNA polymerase (RNAP) suggesting it is an underutilized target. The advent of detailed structural information of... [more]
2015 Bi Y, Ma C, Zhou Z, Zhang T, Zhang H, Zhang X, et al., 'Synthesis and antibacterial evaluation of novel hydrophilic ocotillol-type triterpenoid derivatives from 20(S)-protopanaxadiol', Records of Natural Products, 9 356-368 (2015) [C1]
2015 ACG Publications. All rights reserved.Triterpenoid saponins are involved in plant defense systems to inhibit bacterial invasion. A new series of hydrophilic ocotillol-type... [more]
2014 Mielczarek M, Devakaram RV, Ma C, Yang X, Kandemir H, Purwono B, et al., 'Synthesis and biological activity of novel bis-indole inhibitors of bacterial transcription initiation complex formation', Organic and Biomolecular Chemistry, 12 2882-2894 (2014) [C1]
2014 Keller AN, Yang X, Wiedermannová J, Delumeau O, Krásný L, Lewis PJ, 'e, a new subunit of RNA polymerase found in gram-positive bacteria.', J Bacteriol, 196 3622-3632 (2014)
2014 Withers R, Doherty GP, Jordan M, Yang X, Dixon NE, Lewis PJ, 'AtfA, a new factor in global regulation of transcription in Acinetobacter spp', Molecular Microbiology, 93 1130-1143 (2014) [C1]
2014 John Wiley & Sons Ltd.Acinetobacter species are widely distributed bacteria in the environment, and have recently gained notoriety as opportunistic nosocomial pathogens. H... [more]
2014 Yang X, Ma C, Lewis P, 'A vector system that allows simple generation of mutant Escherichia coli RNA polymerase', PLASMID, 75 37-41 (2014) [C1]
2014 Kandemir H, Kutty SK, Black DS, Kumar N, Ma C, Lewis PJ, Griffith R, 'Synthesis and biological evaluation of 2,5-di(7-indolyl)-1,3,4-oxadiazoles, and 2- and 7-indolyl 2-(1,3,4-thiadiazolyl)ketones as antimicrobials', Bioorganic and Medicinal Chemistry, (2014) [C1]
2014 Bi Y, Ma C, Zhang H, Zhou Z, Yang J, Zhang Z, et al., 'Novel 3-Substituted Ocotillol-Type Triterpenoid Derivatives as Antibacterial Candidates', CHEMICAL BIOLOGY & DRUG DESIGN, 84 489-496 (2014) [C1]
2013 Zhou Z, Ma C, Zhang H, Bi Y, Chen X, Tian H, et al., 'Synthesis and biological evaluation of novel ocotillol-type triterpenoid derivatives as antibacterial agents', European Journal of Medicinal Chemistry, 68 444-453 (2013) [C1]
2013 Ma C, Yang X, Kandemir H, Mielczarek M, Johnston EB, Griffith R, et al., 'Inhibitors of Bacterial Transcription Initiation Complex Formation', ACS Chemical Biology, 8 1972-1980 (2013) [C1]
2013 Brzoska AJ, Hassan KA, de Leon EJ, Paulsen IT, Lewis PJ, 'Single-Step Selection of Drug Resistant Acinetobacter baylyi ADP1 Mutants Reveals a Functional Redundancy in the Recruitment of Multidrug Efflux Systems', PLOS ONE, 8 (2013) [C1]
2012 Buescher JM, Liebermeister W, Jules M, Uhr M, Muntel J, Botella E, et al., 'Global network reorganization during dynamic adaptations of Bacillus subtilis metabolism', Science, 335 1099-1103 (2012) [C1]
2012 Nicolas P, Mader U, Dervyn E, Rochat T, Leduc A, Pigeonneau N, et al., 'Condition-dependent transcriptome reveals high-level regulatory architecture in Bacillus subtilis', Science, 335 1103-1106 (2012) [C1]
Citations Scopus - 235
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