Professor Jeff Cole

Professor Jeff Cole

School of Biosciences
Emeritus Professor of Microbiology

Contact details

Telephone
+44 (0)121 41 45440
Fax
+44 (0)121 41 45925
Email
j.a.cole@bham.ac.uk
Address
School of Biosciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Professor Cole is a microbial physiologist interested in how bacteria adapt to oxygen starvation or excess.  Recent work has focused on how enteric bacteria protect themselves against nitric oxide generated either by other bacteria, or as a protection mechanism of their mammalian hosts.  He currently collaborates with Dr. Amanda Rossiter on projects that include how bacteria survive the human immune response, and their roles in gastric cancer.

Qualifications

Professor Cole is President of the European Federation of Biotechnology

Research

Research Theme within School of Biosciences:Molecular and Cell Biology

Research description

1. Genetic regulation of anaerobic bacterial metabolism of nitrate and nitrite
Oxygen, nitrate and nitrite regulate the synthesis of many enzymes required for bacteria to grow anaerobically. Such 'global responses' involve transcription factors such as FNR, NarL and NarP which respond to signals generated by oxygen, nitrate and nitrite. How are these various regulatory signals coordinated to achieve regulated gene expression? How are the promoters of the genes organised and how do the factors interact with RNA polymerase? This is a joint project with Professor Steve Busby.

2. The molecular and genetic basis of bacterial resistance to human defence mechanisms.
How gonococci invade and survive in the human body have been studied in Birmingham for many years. We are currently interested in the biochemical mechanisms that enable gonococci to adapt to oxygen starvation to explain how they survive both in vivo and in vitro when starved of oxygen. . Microarrays will be used to determine how many operons are regulated by two transcription factors that regulate expression of genes essential for anaerobic survival.

3. Unresolved sources, sinks and pathways for the recovery of enteric bacteria from nitrosative stress
We are attempting to resolve many controversies concerning the sources and mechanisms of reduction of nitric oxide by enteric bacteria, and how nitrosative damage is repaired. The membrane-associated nitrate reductase is the major source of NO generated from nitrite, but at least one other source remains to be identified. Nitrite reductases are primarily detoxification systems that decrease rather than increase the accumulation of NO in the cytoplasm: whether they also catalyse NO formation is unresolved. As none of the three enzymes that reduce NO account for the majority of the rate of NO reduction, additional mechanisms remain to be discovered. Little is known about the biochemistry of damage repair. We are trying to show that the enigmatic hybrid cluster protein is part of a repair pathway rather than a hydroxylamine reductase, as annotated in many genome databases.

4. New bacterial hosts and strategies for generating difficult recombinant proteins in bacteria
Almost any gene can be cloned into a plasmid for expression in a bacterial host, but membrane proteins or proteins that require secretion or extensive post-translational modification often accumulate as unfolded proteins in inclusion bodies. As part of the BBSRC BRIC project and in collaboration with GSK, we are developing novel E. Coli hosts and protocols to produce these difficult proteins in both shake flask and fed-batch fermenters.

Publications

Icke, C., Hodges, F. J., Pullela, K., McKeane, S.A., Bryant, J. A., Cunningham, A. F., Cole, J. A. and Henderson, I. R. (2021) Glycine acylation and trafficking of a new class of bacterial lipoprotein by a composite secretion system. eLife 2021;10:e63762 DOI: 10.7554/eLife.63762.

Cole, J.A. (2021) Anaerobic bacterial response to nitric oxide stress: widespread misconceptions and physiologically relevant responses. Molecular Microbiology  116: 29-40.  doi: 10.1111/mmi.14713.

Hjort, C., Cole, J. and Frebort, I. (2021) European genome editing regulations: threats to the European Bioeconomy and unfit for purpose. Bioeconomy Journal 1 https://doi.org/10.1016/j.bioeco.2021.100001

Goodall, E. C. A., Isom, G. L., Rooke, J. L., Icke, C., Pullela, K., Zhank, B., Rae, J., Tan, W. B., Winkle, M., Delhaye, A., Heinz, E., Cunningham, A. F., Collett, J-F., Blaskovich, M. A., Parton, R. G., Cole, J. A., Chng, S-S., Vollmer, W., Bryant, J. A. and Henderson, I. R. (2021) YhcB coordinates peptidoglycan and LPS biogenesis with phospholipid synthesis during Escherichia coli cell growth.  bioRxiv.

Wu, D., Horn, M. A., Behrendt, T., Müller, S., Li, J., Cole, J. A., Xie, B., Ju, X., Li, G., Ermel, M., Oswald, R., Fröhlich-Nowoisky, J., Hoor, P., Hu, C., Liu, <M.,  Andreae, M. O., Pöschl, U., Cheng, Y., Su, H., Trebs, I., Weber, B. and Sörgel, M. (2019) Soil HONO emissions at high moisture content are driven by microbial nitrate reduction to nitrite: tackling the HONO puzzle.  ISME Journal. ISME J  13: 1688–1699. https://doi.org/10.1038/s41396-019-0379-y

Balasiny, B., Rolfe, M. D., Vine, C. E., Bradley, C., Green, J. and Cole, J. A. (2018). Release of nitric oxide by the Escherichia coli YtfE (RIC) protein and its reduction by the hybrid cluster protein in an integrated pathway to minimise cytoplasmic nitrosative stress.Microbiology 164: 564 – 575. https://doi.org/10.1099/mic.0.000629

Cole, J. A. (2018). Anaerobic bacterial response to nitrosative stress. Advances in Microbial Physiology 72: 193-237 https://doi.org/10.1016/bs.ampbs.2018.01.001

Goodall, E. C. A., Robinson, A., Johnston, I. G., Jabbari, S. Turner, K. A., Lund, P. A., Cole, J. A. and Henderson, I. R. (2018). The essential genome of Escherichia coli K-12. M Bio 9: e02096-17. https://doi.org/10.1128/mBio.02096-17

Castiñeiras, T. S., Williams, S. G., Hitchcock, T., Cole, J. A., Smith, D. C. & Overton, T. W. (2018). Development of a beta-lactamase screening system for selection of signal peptides for periplasmic targeting of recombinant proteins in Escherichia coli. Scientific Reports 8: 6986. https://doi.org/10.1038/s41598-018-25192-3

Castiñeiras, T. S., Williams, S. G., Hitchcock, A., Cole, J. A., Smith, D. C. and Overton, T. W. (2018). Optimising host cell physiology and stress avoidance for the production of recombinant human tumour necrosis factor α in Escherichia coli.  Microbiology 164: 440-452. https://doi.org/10.1099/mic.0.000622

Dunne, K. A., Chaudhuri, R. R., Rossiter, A. E., Beriotto, I., Browning, D. F., Squire, D., Cunningham, A. F., Cole, J. A., Loman, N. and Henderson, I. R. (2017) Sequencing a piece of history: complete genome sequence of the original Escherichia coli strain.  Microbial Genomics 3. doi: 10.1099/mgen.0.000106.

Cadby, I. T., Faulkner, M., Cheneby, J., Long, J., van Helden, J., Dolla, A.and Cole, J. A. (2017). Coordinated response of the Desulfovibrio desulfuricans 27774 transcriptome to nitrate, nitrite and nitric oxide.  Scientific Reports 7: 16228. https://doi.org/10.1038/s41598-017-16403-4

Tutukina, M. N., Potapova, A. V., Cole, J. A. and Ozoline, O. N. (2016) Control of hexuronate metabolism in Escherichia coli by the two interdependent regulators, ExuR and UxuR: derepression by heterodimer formation.  Microbiology 162: 1220 – 1231. https://doi.org/10.1099/mic.0.000297

Cadby, I. T., Ibrahim, S. A., Faulkner, M., Lee, D. J., Browning, D., Busby, S. J., Lovering, Al L. Stapleton, M. R., Green, J. and Cole, J. A. (2016). Regulation, sensory domains and roles of two Desulfovibrio desulfuricans ATCC27774 Crp family transcription factors, HcpR1 and HcpR2, in response to nitrosative stress.  Molecular Microbiology 102: 1120-1137. https://doi.org/10.1111/mmi.13540

Cole, J. A. (2017). Nitric oxide production, damage, and management during anaerobic nitrate reduction to ammonia. Eds. Isabel Moura and José J. G. Moura. In: Denitrification: unravelling Nature’s secrets.  Royal Society of Chemistry. London, UK.

Isom, G. L., Davies, N. J., Chong, Z.-S., Bryant, J. A., Jamshad, M., Sharif, M., Cunningham, A. F., Knowles, T. J., Chang, S.-S., Cole, J. A. and Henderson, I. R. (2017). MCE domain proteins: conserved inner membrane lipid-binding proteins required for outer membrane homeostasis. Scientific Reports 7: 8608. https://doi.org/10.1038/s41598-017-09111-6

Wang, J., Vine, C. E., Balasiny, B. K., Rizk, J., Bradley, C. L., Tinajero-Trejo, M., Poole, R. K., Bergaust, L. L., Bakken, L. R. and Cole, J. A. (2016). The roles of the hybrid cluster protein, Hcp, and its reductase, Hcr, in high affinity nitric oxide reduction that protects anaerobic cultures of Escherichia coli against nitrosative stress. Molecular Microbiology 100: 877-892. https://doi.org/10.1111/mmi.13356

Walton, C., Montoya, M. B., Fowler, D., Turner, C., Jia, W., Whitehead, R., Griffiths, L., Waring, R., Ramsden, D., Cole, J., Cauchi, M., Bessant, C., Naylor, S. and Hunter, J. (2016) Enteral feeding reduces metabolic activity of the intestinal microbiome in Crohn's disease: Observational study.  European Journal of Clinical Nutritio 40: 1052-1056. https://doi.org/10.1038/ejcn.2016.74