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Daniel Bennison
Email:                  djbennison1@sheffield.ac.uk 
​PhD:                     2017-
Department:   Molecular Biology and Biotechnology
Supervisor(s): Dr Rebecca Corrigan (MBB)
                                 Dr John Rafferty (MBB)                                     
​Project: Characterising the mechanisms of (p)ppGpp mediated                               inhibition of Ribosome Associated GTPases in
​                   Staphylococcus aureus. 

Biography: I completed my undergraduate and Master’s degree in Biochemistry and Microbiology from the University of Sheffield in 2017, the latter of which was carried out in the Corrigan lab investigating mechanisms of persister cell formation in Staphylococcus aureus. This involved performing an ORFeome-wide screen to identify proteins which can increase cell survival following exposure to transient doses of antibiotics.

S. aureus is an important human pathogen responsible for a significant amount of infection and morbidity worldwide. With the emergence of methicillin-resistant S. aureus (MRSA), there is an urgent need for novel therapies capable of treating staphylococcal infection. Upon colonisation of the host, bacteria are exposed to multiple stresses, such as nutrient limitation, which can trigger the universally conserved stringent response to cause cellular reprogramming and ultimately survival. This response is mediated via the synthesis of two small effector nucleotides referred to as (p)ppGpp, which have multiple downstream targets and effects which involve slowing growth and arresting the cell cycle, leading to recurrent or chronic infections.

In October 2017, I began my MRC Discovery Medicine North (DiMeN) funded project to investigate the mechanisms by which (p)ppGpp can inhibit the function of four GTPases involved in assembly of the ribosome, namely RsgA, RbgA, Era and HflX. Inhibition of these proteins has been shown to negatively impact ribosomal assembly and hence slow bacterial growth. This project aims to utilise a combination of molecular biology and X-ray crystallography to characterise the interaction between these GTPases and (p)ppGpp in order to increase understanding of how bacteria adapt to conditions of stress, with the overarching motivation being the potential of ribosome inhibition to be used as an antimicrobial therapy.

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The University of Sheffield 
Western Bank 
Sheffield, South Yorkshire 
S10 2TN 

United Kingdom
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