Research Theme within School of Biosciences:Molecular and Cell Biology
Transcriptional regulation in bacteria
Steve Busby’s work concerns the mechanisms by which the expression of different genes is regulated in bacteria. Working with Escherichia coli K-12, over the past 25 years, the lab has elucidated some of the basic rules of promoter recognition by RNA polymerase and some of the fundamental mechanisms by which transcription activators function (see reviews listed below).
The work with RNA polymerase has focused on the roles of the alpha and sigma subunits, whilst the work on transcription activation has developed from studies of the cyclic AMP receptor protein (known as CRP or CAP), which have established a paradigm for understanding transcription activation in bacteria. Early work with CRP, and with the related activator, FNR was concerned with simple promoters, such as the E. coli lac or gal promoters, where one molecule of activator is sufficient for full induction. Recently, the lab has turned its attention to more complicated promoters that are regulated by many different factors. Because bacterial gene expression is exquisitely sensitive to the environment, the majority of promoters are complex and the lab has focused on cases where one molecule of activator is insufficient for full induction.
The work has identified two distinct and novel mechanisms for co-activation of a promoter by multiple activators.
Current active projects concern:
- Analysis of the molecular mechanisms whereby activation at CRP- and FNR-dependent promoters is coupled to other activators. These promoters function as integration devices that coordinate transcriptional responses to different environmental signals.
- How the activity of the major E. coli housekeeping sigma factor is regulated.
- The application of chromatin immunoprecipitation methods to bacteria to monitor the distribution in vivo of RNA polymerase, transcription factors and nucleoid-shaping proteins.
- Promoters that regulate the expression of some of the major virulence determinants of pathogenic E. coli (in collaboration with Mark Pallen and Ian Henderson).
- The relation between the activity of bacterial promoters and their location in bacterial folded chromosomes.
We collaborate with different groups on the UB campus, notably with Jeff Cole (on regulation of gene expression by oxygen and nitrate/nitrite), Dave Grainger (on bcacterial chromosome folding), Josh Rapopport (on imaging), Mark Pallen (on LEE region regulation), Ian Henderson (on the enteroaggregative E. coli toxin) and Laura Piddock (on multidrug resistance in Salmonella). Overseas collaborators include Akira Ishihama (Tokyo), P-S Gunasekaran (Madurai), Kathleen Marchal (Leuven), Dom Schneider (Grenoble) and Victor de Lorenzo (Madrid). Recent overseas visitors have included: Marie-Carmen Martin (Badajoz), Kaneyoshi Yamamoto (Tokyo), Sandra van Puyvelde (Leuven) & Matej Butala (Ljubljana).
Current members of lab
- David Lee, Research Fellow (BSc, PhD, Birmingham): Interactions of bacterial RNA polymerase
- Jennie Mitchell, Research Fellow (BSc, PhD, Birmingham): Interactions of bacterial RNA polymerase
- Maritoni Sanchez-Romero, Research Fellow (BSc, PhD, University of Extramadura): E. coli chromosome biology
- Md Shahidul Islam, (BSc, MSc, Bangladesh Agricultural University): Regulation of LEE gene expression
- Jack Bryant, PhD student (BSc, Birmingham): Consequences of location on transcription in bacteria
- Patchawaran Ruanto, PhD student (BSc, Chiang Mai University; MSc, Birmingham): Genomics of NarL
- Laura Rowley, PhD student (BSc, York): CRP-dependent promoters
- Ghadah AlSharif, PhD student (BSc, King AbdulAziz University; MSc, Aberdeen): Regulation of LEE gene expression
- Rita Godfrey, Technician