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  Role of T and NK-cell immunity during dengue virus infection and impact of immune modulation during therapy


   School of Cellular and Molecular Medicine

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  Dr Laura Rivino  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

A PhD position is available to study the role of human T and NK-cell immunity during infection with dengue virus (DENV), a flavivirus that is transmitted by infected Aedes mosquitoes. DENV infections are increasing dramatically in tropical and sub-tropical countries, with a recent estimate of 390 million infections per year. There is currently no therapeutic available for dengue and the first dengue vaccine has demonstrated only partial protective efficacy - thus highlighting the need to define the immune correlates of protection for dengue. Infection with DENV causes a spectrum of clinical manifestations from asymptomatic infection or self-limiting febrile illness (dengue fever) to severe dengue characterized by plasma leakage, haemorrhagic manifestations which may lead to death. The reasons underlying the progression to severe disease remain poorly defined, but a number of risk factors have been identified and include secondary dengue infection, obesity and age. Obesity in particular has emerged as an important risk factor in South-East Asia, where the large burden of DENV infections occur, as the incidence of obesity is steadily increasing amongst the younger age groups (Gallagher et al J.Infection 2020).

Previous studies performed by our group in collaboration with Dr S.Yacoub’s group at the Oxford University Clinical Research Unit (OUCRU) in Ho Chi Minh City (Vietnam) show evidence of an association between severe disease and CD8+ T and NK-cell dysfunction (Vuong et al J Infect Dis 2022; Chng et al Immunity 2019; Zimmer et al. Nat Comm 2019; Rivino et al Sci Transl Med 2015). Preliminary data from our teams shows that NK and CD8+-T cell dysfunction is exacerbated in young dengue patients with obesity/high BMI compared to those with standard weight– suggesting that immune dysfunction may underlie the increased risk for severe dengue of patients with obesity/high BMI.

This project offers the exciting opportunity to evaluate how metformin, which is being explored by our teams as a potential therapeutic for dengue in obesity, can modulate T and NK-cell responses in vivo, in patients undergoing a clinical trial (Nguyen et al. Wellcome Open Res 2021). The experimental work will utilize dengue patient samples and flow cytometry, cell sorting, live imaging and new methods for metabolic analysis (SCENITH and Metflow), in a recently refurbished CL-3 laboratory (Arguello et al. Cell Metabolism 2020; Ahl et al Communications Biology 2020). There may be opportunities to perform overseas research training at the Emerging Infectious Diseases Department, Duke-NUS Medical School in Singapore, amongst international experts of DENV and flavivirus biology as well as travel to Vietnam and interact with scientists based at our clinical study site at OUCRU, Ho Chi Minh City.

Please include in your application:

- Covering letter stating your interest in the position

- Detailed CV including the names and addresses of two referees

- Copies of your university degree certificate with transcripts

- Evidence of your proficiency in the English language, if applicable.

For further information:

School of Cellular and Molecular Medicine | School of Cellular and Molecular Medicine | University of Bristol


Biological Sciences (4)

Funding Notes

This project is available to international students who wish to self-fund their PhD or who have access to their own funding.

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