Mark Gainford

Email:                   [email protected]
​PhD:                      2020-
Department:   MBB
Supervisor(s): Dr Rebecca Corrigan (MBB)
                                 Dr David Williams (Chemistry)
                                                                    
​Project:  Developing Bacterial Capture Compounds to Identify New Targets Against Antimicrobial Resistant Staphylococcus aureus
Bio: I completed my integrated master’s in Chemistry with Medicinal Chemistry at the University of Leeds in 2019. Where my project focused on the design and multistep synthesis of various novel inhibitors for an unnamed enzyme in the group of Dr Richard Foster.
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Project breakdown:
S. aureus is a major human pathogen that has a significant presence in both clinical and communal settings, with around 30% of the population unknowingly acting as permanent carriers. With the emergence of methicillin-resistant S. aureus (MRSA) and its increasing number of infections, around 12,000 deaths were attributable to the pathogen in 2018-2019. Therefore, the development of novel therapeutics capable of treating staphylococcal infections is paramount.

Bacteria are subject to a variety of external stresses upon colonising a host, such as nutrient deprivation and antimicrobials. These stresses activate the stringent response, a ubiquitous mechanism that increases antimicrobial resistance and bacterial survival through quiescence.

The response is mediated by two signalling nucleotides or “alarmones” - guanosine pentaphosphate (pppGpp) and guanosine tetraphosphate (ppGpp) collectively termed (p)ppGpp. These alarmones interact with a plethora of protein targets involved in transcription and translation, ultimately promoting slowed growth that leads to persistent or chronic infections.

Funded by MRC Discovery Medicine North (DiMeN), I was able to begin my project in October 2020 which focuses on mapping the (p)ppGpp interactome by the design and synthesis of (p)ppGpp structural analogs, along with pull down assays and mass spectrometry. It is hoped that developing our understanding of these alarmone-protein interactions will assist the design of novel therapeutics that can be used in conjunction with current antimicrobials to effectively treat S. aureus infections. 
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