Daniel Bennison shares his experience working on working at the Universidad Peruana de Ciencias Aplicadas in Peru.

In October 2017, I began my MRC DiMeN DTP studentship working alongside Dr. Rebecca Corrigan and Dr. John Rafferty at the University of Sheffield. I work on the bacterium Staphlococcus aureus, which causes a variety of infections and is a significant cause of human disease, often going by its more recognisable name MRSA. My research looks at how these bacteria respond to stressful environments encountered during infection or teatment. More specifically, I aim to determine the mechanism by which ribosome-associated GTPases respond to an internal cellular signal called (p)ppGpp. The overarching motivation for this project includes the potential for ribosome assembly to be targeted by antimicrobial therapy.

​​I was fortunate enough to be awarded MRC Flexible Funding to visit the group of Pohl Milón at UPC in Lima Peru to support a four-week laboratory placement during September 2018. The overall aim of this placement was to learn to utilise their powerful and state of the art stopped-flow equipment to study enzyme kinetics, as well as the kinetics of complex formation (ie. Kon, Koff and Kd) between the GTPases in question and the ribosome itself, and expand my own appreciation of the subject of biochemical kinetics.

​Following the initial week of training, I became independent while using the equipment and as such was able to tailor the experimental conditions to suit my own needs, generating a large amount of high quality data while still being able and encouraged to consult with the other members of this group for advice. In addition to learning this new technique, this placement allowed me to work alongside world leaders in this field, meet some friends for life and forge a fruitful collaboration between our labs that should last for many years. As a result of this, I have expanded the scope of my project hugely which will benefit the quality of my research but also my overall PhD experience.

​​Aside from the science, this trip abroad to a country so different to ours really served to broaden my horizons and experience living and working in a completely different environment, a skill that is becoming increasingly necessary due to the collaborative nature of science. Needless to say, this trip not only met, but exceeded my academic and cultural expectations and all in all was a fantastic experience. Thanks again to the MRC and DiMeN DTP for this amazing opportunity. 

Taking in Machu Picchu before enjoying a short break before my return to the UK. 

Florey Institute research fellow Dr Rebecca Corrigan has been awarded the prestigious Lister Fellowship from the Lister Institute of Preventative Medicine (http://www.lister-institute.org.uk/). This award will fund Dr Corrigan's research on the human pathogen Staphylococcus aureus (also known as MRSA) for the next five years.

Infections caused by Staphylococcus aureus/MRSA can be severe and life threatening requiring the use of antibiotics. Some bacteria are able to survive these treatments by switching into a non-growing less active state called persistence. Dr Corrigan’s research will focus on how bacteria switch into this persistent state to understand antibiotic tolerance and bacterial growth during infections.

​We are currently investigating the atomic details of the flagellum tip, to try and understand how it adheres onto human cells. We are also trying to decipher the architecture of the “basal body”, the region of the flagellum that is anchored at the bacterial surface and that acts as an anchoring point for its assembly. Ultimately, our research could be exploited to generate new antibiotics that block the formation or function of the flagellum.

Read more about Julien's research at: www.bergeronlab.com
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Using the latest microscopy to rethink the model of bacterial growth and division

The cell wall is a structure surrounding bacteria and is essential for structural support, it is often a target for antibiotic treatment for this very reason.

The ‘building blocks’ of this cell wall is peptidoglycan, this is a long chain formed of sugars and amino acids that provides a structural role.

To create this incredibly important structure the cell has to coordinate the process. In S. aureus synthesis of this begins at the middle of the cell and is guided by dynamic cell wall synthesis machines.

An interesting finding of this paper is that not all peptidoglycan insertion occurs at the leading edge of the septum in this species, causing researchers to rethink the model in which they look at S. aureus cell division.

To read the full article and find out more about how the techniques which generated  these images, follow this link

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​This finding links cell wall growth to many other developmental processes within the cell and further work will help us to understand how the MacP-switch operates and, ultimately, what signals trigger the function of the cell wall building machines.

Dr Fenton, who led the study in Sheffield, explains:

“The last few years has seen a revolution in the way we think about cell wall growth in bacteria. Recent findings have redefined the biochemical activities of many factors we thought we understood. This paradigm shift has opened many exciting lines of investigation, including how the cell wall building machinery is regulated.”

“It is now clear that different types of bacteria approach the regulation of cell wall growth in different ways. This study breaks new ground in our understanding and links cell wall growth to central regulatory processes within the bacterial cell.”
 
“With bacteria pushing back against antibiotic treatment there is an ever-increasing burden on current clinical practices. Cell wall growth remains one of most widely used targets when treating bacterial infections. Therefore, there has never been a more urgent need for us to understand these processes.”
 
The full paper entitled: Phosphorylation-dependent activation of the cell wall synthase PBP2a in Streptococcus pneumoniae by MacP has been published recently in PNAS (Proceeding of the National Academy of Sciences). READ IT HERE.

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​We have found a new way to study how infections enter the brain and how we might prevent the damage they cause during meningitis.
  
We are using the zebraifsh to study human infections and meningitis. Zebrafish have translucent bodies that means we can study how infections enter the brain and how they cause damage. 

We are now using this technique to find new treatments for meningitis."

Dr Johnston's lab published a manuscript last month looking how zebrafish can be used to study these processes.

​For more information see paper LINKED HERE.
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