Dr Douglas F. Browning BSc(Hons) PhD

Dr Douglas F. Browning

School of Biosciences
Senior Research Fellow

Contact details

Address
School of Biosciences
University of Birmingham
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Dr Doug Browning is a Senior Research Fellow in the School of Biosciences and the Institute of Microbiology and Infection. His research focuses on three main areas: 1) how pathogenic bacteria regulate gene expression in response to multiple environmental and metabolic signals, 2) how the outer membranes of Gram-negative bacteria are assembled and how they can be disrupted and 3) the use of synthetic biology to design new bacterial recombinant protein expression systems.

Google Scholar Profile: http://scholar.google.co.uk/citations?hl=en&user=xZF8C8IAAAAJ

Research Gate Profile: http://www.researchgate.net/profile/Douglas_Browning

Qualifications

  • PhD in Microbiology, University of Warwick
  • BSc (Hons) in Biological Sciences (Genetics), University of Birmingham

Biography

Doug Browning graduated from the University of Birmingham with a degree in Biological Sciences before moving to the University of Warwick to carry out his Ph.D. in Microbiology. After its completion, he moved back to Birmingham and now investigates the regulation of gene expression in bacterial pathogens, the biogenesis of outer membranes in Gram-negative bacteria and the use of synthetic biology to design new bacterial expression systems.

Teaching

  • Delivery of various lectures and tutorials.
  • Undergraduate tutor.
  • Supervision of undergraduate and MSc laboratory based research projects.
  • Tutor for the “Access to Birmingham (A2B)” initiative.

Postgraduate supervision

Doug Browning currently supervises two PhD students, investigating the regulation of gene expression in pathogenic Enteroaggregative Escherichia coli (EAEC).

Research

Regulation of bacterial virulence. During their transition through the mammalian gut, enteric bacteria experience many harsh environmental conditions, having to cope with limited nutrients, low oxygen tensions and the presence of toxic molecules. Thus, to survive and cause disease, enteric pathogens must sense their environment and adapt by altering their patterns of gene expression. This is largely achieved by controlling transcription initiation and in many cases involves the interplay of several global transcription factors at promoter regions. Doug Browning’s research examines how global transcription factors (e.g. CRP, FNR, AggR and NarL) and protein factors which fold the bacterial chromosome (e.g. IHF, Fis and HNS) can coordinate genome wide gene expression in pathogens such as enteroaggregative E. coli (EAEC), Shigella flexneri and Salmonella enterica serovar Typhimurium.

Insertion of b-barrel membrane proteins into the outer membranes of bacteria. Gram-negative bacteria have an outer membrane that functions as a barrier to protect the bacterium from toxic compounds such as antibiotics and detergents. It is composed of phospholipids, lipopolysaccharide (LPS) and two major classes of proteins, lipoproteins and integral b-barrel outer membrane proteins (OMPs). Insertion of OMPs in E. coli is an essential process and is carried out by the BAM complex (b-barrel assembly machinery). In E. coli this multi-protein complex consists of the OMP BamA and four accessory lipoproteins (BamB, BamC, BamD and BamE). Doug Browning’s research examines how the BAM complex orchestrates the folding and insertion of OMPs into the outer membrane of E. coli and how this machinery differs in other important Gram-negative bacteria, such as Haemophilus influenzae, Pseudomonas aeruginosa and Neisseria meningitidis.

Engineering of bacterial systems for recombinant protein production. Many of the bacterial recombinant protein production (RPP) systems currently used for RPP were developed in the 1980’s and are often unsuited for the production of high quality therapeutic products, such as antibodies. My current research aims to overcome many of the problems associated with bacterial RPP systems by engineering promoters, plasmids and strains to achieve coordinated and sustainable RPP to improve both product yield and quality

Other activities

Co-Chair of UKRSA/ Vitae (UK Research Staff Association)

Midlands Regional Representative for UKRSA

https://ukrsavitae.wixsite.com/ukrsa/the-team

Local Network Lead for UK Reproducibility Network (UKRN)

https://www.ukrn.org/local-network-leads/

Member of the Microbiology Society.

Elected member of the Microbiology Society Professional Development (PDC) Committee (2015-20).

University of Birmingham Administration:

1)      Member of the School of Biosciences Safety Committee.

2)      Member of the PERCAT (Postdoctoral/ Early Career Development and Training) Committee.

3)      Member of the College of Life and Environmental Sciences Research and Knowledge Transfer Committee.

4)      Chief Editor of the School of Biosciences Mole Newsletter.

Publications

Key Review Articles:

1) Browning, D.F., Butala, M., Busby, S.J.W. (2019) Bacterial Transcription Factors: Regulation by Pick "N" Mix. Journal of Molecular Biology. 431(20):4067-4077.

2) Browning, D.F.*, Godfrey, R.E., Richards, K.L., Robinson, C. and Busby, S.J.W. (2019) Exploitation of the Escherichia coli lac operon promoter for controlled recombinant protein production. Biochemical Society Transactions. 47:755-763. *Corresponding author.

3) Browning, D. F.* andBusby, S. J. W. (2016) Local and global regulation of transcription initiation in bacteria. Nature Microbiology Reviews. 14:638-650. *Corresponding author.

4) Fornelos, N and Browning, D. F.* andButala, M. (2016) The use and abuse of LexA by mobile genetic elements. Trends in Microbiology. 24:391-401. *Corresponding author.

5) Browning, D.F., Grainger, D. C. and Busby, S. J. W. (2010) Effects of nucleoid-associated proteins on bacterial chromosome structure and gene expression. Current Opinion in Microbiology. 13:773-780.

6) Browning, D. F. andBusby, S. J. W. (2004) The regulation of bacterial transcription initiation. Nature Microbiology Reviews. 2: 57-65.

Published Research Articles since 2010 (updated January 2021):

1) Abdelwahab, R., Yasir, M., Godfrey, R.E., Christie, G.S., Element, S.J., Saville, F., Hassan, E.A., Ahmed, E.H., Abu-Faddan, N.H., Daef, E.A., Busby, S.J.W. and Browning, D.F.* (2021) Antimicrobial resistance and gene regulation in Enteroaggregative Escherichia coli from Egyptian children with diarrhoea: similarities and differences. Virulence. 12:57-74. *Corresponding author.

2) Ruanto, P., Chismon, D.L., Hothersall, J., Godfrey, R.E, Lee, D.J,Busby, S.J.W. and Browning, D.F.*. (2020) Activation by NarL at the Escherichia coli ogt promoter. Biochemical Journal. 477:2807-2820. *Corresponding author.

3) Hooper, C.A.J., Cardo, L., Craig, J.S., Melidis, L., Garai, A., Egan, R.T., Sadovnikova, V., Burkert, F., Male, L. Hodges, N.J., Browning, D.F., Rosas, R.,  Liu, F., Rocha, F.V., Lima, M.A., Liu, S., Bardelang, D. and Hannon, M.J. (2020) Rotaxanating metallo-supramolecular nano-cylinder helicates to switch DNA junction binding. J. Am. Chem. Soc. 142(49):20651-20660. 

4) Bryant, J.A., Morris, F.C., Knowles, T.J., Maderbocus, R., Heinz, E., Boelter, G., Alodaini, D., Colyer, A., Wotherspoon, P.J., Staunton, K.A., Jeeves, M., Browning, D.F., Sevastsyanovich, Y.R., Wells, T.J., Rossiter, A.E., Bavro, V.N., Sridhar, P., Ward, D.G., Chong, Z.S., Goodall, E.C.A., Icke, C., Teo, A., Chng, S.S., Roper, D.I., Lithgow, T., Cunningham, A.F., Banzhaf, M., Overduin, M. and Henderson, I.R. (2020) Structure of dual-BON domain protein DolP identifies phospholipid binding as a new mechanism for protein localization. Elife. 9:e62614.

5) Écija-Conesa, A., Gallego-Jara, J., Terol, G.L., Browning, D.F., Busby, S.J.W., Wolfe, A.J., Díaz, M.C., de Diego Puente, T. (2020) An ideal spacing is required for the control of Class II CRP-dependent promoters by the status of CRP K100. FEMS Microbiol Letters. 367(20):fnaa164. 

6) Connolly, J.P.R., O’Boyle, N., Turner, N., Browning, D.F. and Roe, A.J. (2019) Distinct intra-species virulence mechanisms regulated by a conserved transcription factor. PNAS. 116:19695-19704.

7) Guerrero-Montero, I., Richards, K.L., Browning, D.F., Peswani, A.R, Labrit, M., Allen, M., Aubry, C., Davé, E., Humphreys, D.P., Busby, S.J.W. and Robinson, C.(2019) TatExpress strains export over 5g/L human growth hormone to the periplasm by the Tat pathway. Biotechnology and Bioengineering. 116:3282-3291.

8) Nieminen, L. Lemonidis, K., Browning, D., Hunter, I., Suckling, C. and Tucker, N. (2019) Transcriptomic analysis indicates the mode of action of the novel antibiotic MGB-BP-3 against Staphylococcus aureus. Access Microbiology. 1 (1A), 679.

9) Yasir, M., Icke, C., Abdelwahab, R., Haycocks, J.R., Godfrey, R.E., Sazinas, P., Pallen, M.J., Henderson, I.R., Busby S.J.W. and Browning, D.F.* (2019) Organization and architecture of AggR-dependent promoters from Enteroaggregative Escherichia coli. Molecular Microbiology. 111:534-551. *Corresponding author.

10) Ellis, S.J., Yasir, M., Browning, D.F., Busby, S.J.W and Schüller, S. (2019) Oxygen and contact with human intestinal epithelium stimulate virulence gene expression in enteroaggregative Escherichia coli. Cellular Microbiology. e13012.

11) Fornelos, N., Browning, D.F.*, Pavlin, A., Podlesek, Z., Hodnik, V, Salas, M. and Butala, M. (2018) Lytic gene expression in the temperate bacteriophage GIL01 is activated by a phage-encoded LexA homologue. Nucleic Acids Research. 46:9432-944.*Corresponding and joint first author.

12) Browning, D.F.*, Richards, K.L., Peswani, A.R., Roobol, J., Busby, S.J.W. and Robinson, C. (2017) Escherichia coli 'TatExpress' strains super-secrete human growth hormone into the bacterial periplasm by the Tat pathway. Biotechnology and Bioengineering. 114(12):2828-2836. *Corresponding author.

13) Godfrey, R.E., Lee, D.J., Busby, S.J. and Browning, D.F.* (2017) Regulation of nrf operon expression in pathogenic enteric bacteria: sequence divergence reveals new regulatory complexity. Molecular Microbiology. 104:580-594. *Corresponding author.

14) O'Donoghue, E.J., Sirisaengtaksin, N., Browning, D.F., Bielska, E., Hadis, M., Fernandez-Trillo, F., Alderwick, L., Jabbari, S. and Krachler, A.M. (2017) Lipopolysaccharide structure impacts the entry kinetics of bacterial outer membrane vesicles into host cells. PLoS Pathogens 13(11):e1006760.

15) Sevastsyanovich, Y., Withers, D., Marriott, C., Morris, F., Wells, T., Browning, D.F., Beriotto, I., Ross, E. Ali, H., Wardius, C., Cunningham, A., Henderson, I and Rossiter, A. (2017) Antigen localisation influences the magnitude and kinetics of the endogenous adaptive immune response to recombinant Salmonella vaccines. Infection and Immunity. 85(12) e00593-17.

16) 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(3).

17) Cadby, I.T., Ibrahim, S.A., Faulkner, M., Lee, D.J., Browning, D., Busby, S.J., Lovering, A.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.

18) Kamenšek, S., Browning, D.F*, Podlesek, Z., Busby, S.J.W., Žgur‑Bertok, D. and Butala, M. (2015) Silencing of DNase colicin E8 gene expression by a complex nucleoprotein assembly ensures timely colicin induction. PLOS Genetics. 11(6):e1005354. *Corresponding and joint first author.

19) Browning, D.F.*, Bavro, V.N., Mason, J.L., Sevastsyanovich, Y.R., Rossiter, A.E., Jeeves, M., Wells, T.J., Knowles, T.J., Cunningham, A.F., Donald, J.W., Palmer, T., Overduin, M. and Henderson IR. (2015) Cross-species chimeras reveal BamA POTRA and β-barrel domains must be fine-tuned for efficient OMP insertion. Molecular Microbiology. 97:646-59. *Corresponding author.

20) Rossiter, A.E, Godfrey, R.E., Connolly, J.A., Busby, S.J.W., Henderson, I.R. and Browning, D.F. * (2015) Expression of different bacterial cytotoxins is controlled by two global transcription factors, CRP and Fis, that cooperate in a shared-recruitment mechanism. Biochemical Journal. 466:323-35. *Corresponding author.

21) Timothy J. Wells, T.J., Whitters, D., Sevastsyanovich, Y.R., Heath, J.N., Pravin, J., Goodall, M., Browning, D.F., O’Shea, M.K., Cranston, A., De Soyza, A., Cunningham, A.F., MacLennan, C.A., Henderson, I.R. and Stockley, R.A. (2014)Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing.Journal of Experimental Medicine. 211:1893-1904.

22) Browning, D.F. *, Matthews, S.A., Rossiter, A.E., Sevastsyanovich, Y.R., Jeeves, M., Mason, J.L., Wells, T.J., Wardius, C.A. Knowles, T.J., Cunningham, A.F., Bavro, V.N., Overduin, M., Henderson, I.R. (2013) Mutational and Topological Analysis of the Escherichia coli BamA protein. PLOS ONE 10.1371/journal.pone.0084512. *Corresponding author.

23) França, F.L.S., Wells, T.J, Browning, D.F., Nogueira, R.T., Sarges, F.S., Pereira, A. C., Cunningham, A.F., Lucheze, K., Rosa, A.C.P., Henderson, I.R. and das Graças de Luna, M. (2013) Genotypic and phenotypic characterisation of enteroaggregative Escherichia coli from children in Rio de Janeiro, Brazil.PLOS ONE 10.1371/journal.pone.0069971.

24) Browning, D.F.*, Wells, T.J., França, F.L.S., Johnson, M.D., Morris, F.C., Bryant, J.A., Lund, P.A., Cunningham, A.F., Hobman, J.L., May, R.C., Webber, M.A. and Henderson, I.R. (2013) Laboratory adapted Escherichia coli K-12 becomes a pathogen of Caenorhabditis elegans upon restoration of O antigen biosynthesis. Molecular Microbiology. 87:939-50.*Corresponding author. Faculty of 1000 recommended.

25) Butala, M, Sonjak, S., Kamenšek, S., Hodošček, M., Browning, D.F., Žgur‑Bertok, D and Busby, S.J.W. (2012) Double locking of an Escherichia coli promoter by two repressors prevents premature colicin expression and cell lysis. Molecular Microbiology. 86:129-39.

26) Leyton, D.L., Sevastsyanovich, Y.R., Browning, D.F., Rossiter, A.E, Wells, T.J., Fitzpatrick, R.E., Overduin, M., Cunningham, A.F. and Henderson, I.R. (2011) Size and shape matter: the autotransporter secretion pathway is intrinsically unable to secrete large disulphide-bonded regions. Journal of Biological Chemistry. 286:42283-42291.

27) Raghunathan, D., Wells, T.J., Morris, F.C., Shaw, R.K., Bobat, S., Peters, S.E., Paterson, G.K., Tveen-Jensen, K., Leyton, D.L., Blair, J.M.A., Browning, D.F., Pravin, J., Flores-Langarica, A., Hitchcock, J.R., Moraes, C.T.P.5, Piazza, R.M.F., Maskell, D.J., Webber, M.A., May, R.C., MacLennan, C.A., Piddock, L.J., Cunningham, A.F. and Henderson, I.R. (2011) SadA, a trimeric autotransporter from Salmonella enterica Typhimurium, can promote biofilm formation and provides limited protection against infection. Infection and Immunity. 79:4342-4352.

28) Rossiter, A. E., Leyton, D. L., Tveen-Jensen, K., Browning, D. F., Sevastsyanovich, Y., Knowles, T. J., Nicols, K., Cunningham, A. F., Overduin, M., Schembri, M. A. and  Henderson, I. R. (2011) The essential BAM complex components BamD and BamA are required for autotransporter biogenesis. Journal of Bacteriology. 193:4250-4253.

29) Rossiter, A.E., Browning, D.F., Leyton, D.L., Johnson, M.D., Godfrey, R.E., Wardius, C.A, Desvaux, M., Cunningham, A.F., Ruiz-Perez, F., Nataro, J.P.,  Busby, S.J.W. and  Henderson, I.R. (2011) Transcription of the plasmid-encoded toxin gene from Enteroaggregative Escherichia coli is regulated by a novel co-activation mechanism involving CRP and Fis. Molecular Microbiology. 81:179-191.

30) Clarke, D.J., Chaudhuri, R.R., Martin, H.M., Campbell, B.J., Rhodes, J.M., Constantinidou, C., Pallen, M.J., Loman, N.J., Cunningham, A.F., Browning, D.F. andHenderson, I.R. (2011) Complete genome sequence of the Crohn's disease-associated adherent-invasive Escherichia coli strain HM605. Journal of Bacteriology. 193:4540.

31) Knowles, T.J., Browning, D.F. *, Jeeves, M., Maderbocus, R., Rajesh, S., Sridhar, P., Manoli, E., Emery, D., Sommer, U., Spencer, A., Leyton, D.L., Squire, D., Chaudhuri, R.R., Viant, M.R., Cunningham, A.F., Henderson, I.R. and Overduin, M.  (2011) Structure and function of BamE within the outer membrane and the β-barrel assembly machine. EMBO Reports. 12:123-128. *Joint first author.

32) Leyton, D. L., Graças de Luna, M., Sevastsyanovich, Y. R., Jensen, K. T., Browning, D. F., Scott-Tucker, A. and Henderson, I. R. (2010) The unusual extended signal peptide region is not required for secretion and function of an Escherichia coli autotransporter. FEMS Microbiology Letters. 311:133-139.

33) Chismon, D. L., Browning, D. F., Farrant, G. K. and Busby, S. J. W. (2010) Unusual organisation, complexity and redundancy at the Escherichia coli hcp-hcr operon promoter. Biochemical Journal. 430: 61-68.

34) Browning, D. F.*, Lee, D. J., Spiro, S. and Busby, S. J. W. (2010) Down-regulation of the Escherichia coli K-12 nrf promoter by binding of the NsrR nitric oxide sensing transcription repressor to an upstream site. Journal of Bacteriology. 192:3824-3828. *Corresponding author.

35) Marteyn, B., West, N. P., Browning, D. F., Cole, J. A., Shaw, J. G., Palm, F., Mounier, J., Prévost, M., Sansonetti, P. and Tang, C. M.(2010) Modulation of Shigella virulence in response to available oxygen in vivo. Nature. 465:355-358. Faculty of 1000 recommended.

 Published Book Chapters:

1) Browning, D. F., Grainger, D. C., Xu, M. and Busby, S. J. (2010)Transcriptional regulation by nucleoid-associated proteins at complex promoters in Escherichia coli. In Bacterial Chromatin (Dame and Dorman (eds)). pp 419-443. Springer, Netherlands.

2) Browning, D., Savery, N., Kolb, A. and Busby, S. (2009) Assays for Transcription Factor Activity. In Methods in Molecular Biology, DNA-protein Interactions. (Moss and LeBlanc (eds)) pp 369-387. Humana Press, NJ, USA.

3) Browning, D. F., Grainger, D. C. and Busby, S. J. (2009) Organisation of complex Escherichia coli promoters.In Systems Biology and Biotechnology of E. coli (Lee (ed)) pp 257-271. Springer, Netherlands.

4) Browning, D., Lee, D., Green, J. and Busby, S. J. W. (2002) Secrets of bacterial transcription initiation taught by the Escherichia coli FNR protein. In Signals, Switches, Regulons, and Cascades (Hodgson and Thomas (eds)) pp 127-142. Cambridge University Press, Cambridge, UK.

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