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Understanding and targeting the molecular mechanisms of dengue virus protein synthesis


Faculty of Health & Medical Sciences

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Prof N Locker No more applications being accepted Funded PhD Project (European/UK Students Only)

About the Project

Project:  

Our aim is to understand a new mechanism of protein production by mosquito-borne viruses and develop novel therapeutics for diseases of clinical and economical importance.   

During infection, host cells can initiate stress responses to shut down their translation machinery which viruses rely on for their own protein synthesis. In consequence, many viruses have engineered alternative translation pathways to commandeer the host machinery and produce viral proteins. 

We have uncovered a new mechanism of protein synthesis by dengue virus (DENV). We have robust evidence that during infection, a known cellular translation factor eIF3 is repurposed, in a non-conventional manner, to mediate viral translation by interacting with the DENV RNA. 

Therefore, our objectives are to characterize the mechanism by which eIF3 interacts with DENV RNA, how it drives protein synthesis and translate this novel paradigm into antiviral drugs blocking DENV, and other flaviviruses such as Yellow Fever Virus, replication with the support our industrial partner EditForce.  

Supervisors: 

Dr Nicolas Locker (NL) is a Professor of Virology and Head of the virology section. NL’s research group focuses on understanding virus-host interactions and the regulation of gene expression and translational control during infections through BBSRC-funded projects. He recently showed how norovirus modulate host translation by regulating translation initiation factor activity, and that some of these mechanisms are conserved during dengue virus infection. Dr Kevin Maringer (KM) is a Group leader at the Pirbright Institute. KM’s research focusses on molecular interactions between dengue virus (DENV) and its human and insect hosts. Ongoing MRC-funded projects are using DENV infection assays, viral reverse genetics, transcriptomics, proteomics and molecular tools to elucidate DENV immune evasion strategies.  


Funding Notes

The funding package for this studentship award is as follows:
Full UK/EU tuition fee covered
Stipend at £15,285 p.a. (2020/21)
RTSG of £1,000 p.a.
Contribution to bench fees of £5,000 p.a (provided by the Faculty)
Personal Computer (provided by the department)
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