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WELCOME TO THE BLOWER LAB

 

ABOUT

Established at Durham University, UK, in 2015 by Dr Tim Blower, our lab combines microbiology, genomics, biochemistry and X-ray crystallography to better understand bacteria and the viruses that infect them, known as bacteriophages or 'phages'.

Inset: phage Smiley, isolated from waterways around Durham and visualised by transmission electron microscopy as part of our undergraduate phage workshop.

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OUR RESEARCH

Bacteria have evolved to survive a wide range of environmental, antibiotic, immunological and viral assaults. 

The survival mechanisms employed by bacteria need to be understood in order to utilise the extensive biological toolkit they represent, and to beat the rise of hyper-resistant superbugs.

We take a multifaceted approach, using E. coli and Salmonella model systems, to investigate the genetics, biochemistry and structural biology of bacterial survival mechanisms, namely bacterial phage-resistance and toxin-antitoxin systems.

 
 
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We purify proteins and grow them as crystals

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PHAGE-RESISTANCE SYSTEMS

Bacteria are outnumbered about 10 to 1 by viruses called bacteriophages. These bacteriophages (or 'phages') create a huge evolutionary pressure that drives bacterial evolution, generating a wide range of bacterial phage-resistance systems that have been co-opted as useful biotechnologies. Examples include restriction-modification systems and CRISPR-Cas.


As bacteria continue to gain resistance to our antibiotics, there has also been a recent resurgence of interest in using phages as a targeted means to stop bacterial infections, through "phage therapy".

Understanding phage-host interactions is essential for developing new biotechnologies and validating phage therapies. 

To this end, we are investigating the abortive infection and Bacteriophage Exclusion (BREX) phage-resistance systems, using a range of phages that we isolate from the local environment.


Inset: Abortive infection system AbiEi from Streptococcus agalactiae 

 

TOXIN-ANTITOXIN SYSTEMS

These predominantly two-gene systems typically encode a toxic protein and an antagonistic antitoxin. They can be used to protect from phages and stabilise genetic elements, and in some cases allow bacteria to survive antibiotics. Though seemingly unintuitive, individual bacterial cells produce these toxins to slow and stop their own growth, which allows for survival of the clonal bacterial population around them.

We are investigating a range of toxin-antitoxin systems from key human pathogens, to learn how these toxins work and therefore how we might develop new ways to manage bacterial populations.

Inset: MenT toxins from Mycobacterium tuberculosis

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TOPOISOMERASES

All cells contain essential enzymes to manipulate and maintain DNA topologies. These topoisomerases are key targets for anticancer drugs in humans, and antibiotics in bacteria.

We are investigating proteins that interfere with topoisomerase activity, to better understand topoisomerase biochemistry and define new potential means for their control.

Inset: DNA gyrase from Mycobacterium tuberculosis bound to DNA (orange ribbons) and the antibiotic moxifloxacin (green spheres)

 

Blower Lab

©2020 by Tim Blower