BSc (Hons) First Class - John Butterfield Prize awardee, University of Birmingham (2008); PhD, University of Birmingham (2013); Postdoctoral Research Fellow, School of Biosciences, University of Birmingham (2013-2015); Postdoctoral Research Fellow, Medical and Dental Sciences, University of Birmingham (2015-2022); Postdoctoral Research Fellow, School of Biosciences, University of Birmingham (2022-2023); Nottingham Research Fellow, University of Nottingham (2023-Present)
Jack Bryant is an expert in Gram-negative bacterial envelope biology, gene regulation and chromosome biology. Jack has expertise in high-throughput genetics approaches in bacteria, chromosome engineering and protein biochemistry
Drug-resistant bacterial infections are one of the biggest threats to global public health and cause 1.27 million deaths annually. Currently, three quarters of World Health Organisation-listed… read more
Drug-resistant bacterial infections are one of the biggest threats to global public health and cause 1.27 million deaths annually. Currently, three quarters of World Health Organisation-listed critical research priority pathogens are Gram-negative bacteria. These bacteria have an additional membrane, the outer membrane (OM), that acts as a barrier against the entry of antibiotics into the cell. Despite the importance of Gram-negative envelopes as an innate antimicrobial defence, we do not fully understand how they are built and may be missing opportunities for new drug targets.
Central to the construction of the OM is a multi-protein machine, the beta-barrel assembly machine (Bam) complex, which is responsible for folding and insertion of proteins into the OM. The Bam complex is essential for growth and its components are conserved throughout all Gram-negative bacteria. Not only is the Bam complex essential to survival, but reduction of Bam activity leads to increased cell permeability and susceptibility to drugs that Gram-negatives are normally resistant to. Therefore, inhibitors of the complex would not only act as attractive antimicrobials in their own right, but could potentially increase the efficacy of existing antibiotics to which resistance has developed. Despite intensive study, the surveillance and quality control mechanisms to ensure faithful OM protein folding by the BAM complex are poorly understood and discovery of drugs that target the BAM complex is significantly under-exploited.
My research directly addresses these two issues by:
(a) using the high-throughput power of transposon mutagenesis, targeted genetics, biochemistry and structural biology to investigate a family of proteases in Escherichia coli that are thought to be part of a surveillance mechanism that roots out incorrectly folded OMPs, and
(b) developing high-throughput assays for OM protein biogenesis to enable discovery and optimisation of antimicrobials that inhibit this druggable target in key Gram-negative pathogens.
Overall, this work will aid in the identification of potential drug targets and help to overcome the molecular barrier posed by the outer membrane, ultimately leading to better treatment of Gram-negative bacterial infections.
Outside of my work on Gram-negative bacterial envelope biology, I have experience in bacterial gene regulation, chromosome biology, antimicrobial surface technologies and drug delivery systems for the human eye. During my PhD, I worked with Professor Steve Busby to study the impact of chromosome folding on transcription in bacteria. Regulation of bacterial gene expression was previously thought to be relatively simple, especially compared to that of eukaryotes. My work defined bacterial position effects for the first time, demonstrating that position of a promoter/gene within the chromosome significantly impacts the level of gene expression. This study garnered significant interest and began the field of position effects in bacteria, initiating multiple new lines of enquiry in fundamental bacterial genetics and the development of bacterial strains for synthetic biology. I continued this work during a short postdoc position where we showed that RNA polymerase supply plays a role in position-dependent variation in gene expression and that mobile antimicrobial resistance genes encoded on transposable elements are also subject to position effects. This has significant implications for the evolution of antimicrobial resistance and prediction of resistance from DNA sequence as changes in location can change the level of resistance.
More recently I worked with Dr. Felicity de Cogan (UoB - MDS) on the development and commercialisation of antimicrobial surface technologies that kill Gram-negative bacteria on contact and drug delivery systems for the human eye. Our work on drug delivery formulations for eye medications was very successful and has contributed to the establishment of a spin-out company to further develop this technology. Felicity and I continue collaboration on the mode of action of antimicrobial surface technologies.