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Overview

Professor Tim Blower

Professor


Affiliations
Affiliation
Professor in the Department of Biosciences
Visiting Associate Professor in the Department of Chemistry
Member of the Biophysical Sciences Institute
Biophysical Sciences Institute Executive Board in the Biophysical Sciences Institute

Biography

Toxin-antitoxin systems and bacteriophage-resistance

Whilst bacteria are often thought of as selfish cells working for their own benefit, we can observe that they exist as diverse interacting communities. This is reflected in the ubiquitous presence and implementation of "toxin-antitoxin" systems throughout known Bacterial and Archaeal species. Toxin-antitoxin systems are characterised as small genetic loci generally encoding two parts. The toxin, when free to act, will target the host cell and stall growth. In the presence of the antitoxin, this effect is negated and cells grow freely.

It might appear peculiar that bacterial cells carry toxin-antitoxin systems, until you consider the potential advantages. For instance, if there aren't enough nutrients to go around, one cell activates its internal toxins, allowing it to grow slower or die, so that the population of clonal bacteria around it can survive. Another example would be when a bacterial cell becomes infected by a bacteria-specific virus, called a bacteriophage (phage). Unchecked, the phage would replicate, burst out, and infect neighbour cells. If the infected cell shuts down quickly, however, it can stop viral spread and protect the bacterial population.

Toxins from toxin-antitoxin systems often target the same biomolecules as antibiotics. Studying how these toxins kill bacteria will allow us to develop new ideas and methods for stopping bacterial infections.

Figure 1. The BrxU DNA-modification dependent restriction enzyme targets modifed phage DNA for cleavage. This crystal structure shows an intertwined BrxU dimer, with each monomer coloured in cyans or pinks. See Picton et al. 2021, Nucleic Acids Research 49(19): 11257-11273.

Harnessing molecular tools from phage-host interactions

The interactions between phages and their bacterial hosts have generated a wealth of tools used in biotechnology, including CRISPR-Cas systems and restriction enzymes (Figure. 1). 

As the natural predators of bacteria, it is also essential to investigate phage-host interactions in order to develop phages as a viable therapeutic alternative to antibiotics.

We investigate toxin-antitoxin systems and phage-host interactions using a range of molecular biology, microbiology, genetic and biochemical techniques. These include protein biochemistry, genomics and structural analysis through X-ray crystallography.

Research interests

  • Antimicrobial Resistance
  • Bacteriophage biology
  • Biochemistry
  • Molecular Microbiology
  • Structural Biology
  • Toxin-antitoxin systems
  • Phage defence

Esteem Indicators

Publications

Journal Article

Supervision students