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PhD in Infection & Immunity - Modifying human cytomegaloviruses to drive expansion of effector natural killer and cytotoxic T cells

  • Full or part time
    Dr E Wang
  • Application Deadline
    Wednesday, February 27, 2019
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Natural Killer (NK) cells and CD8+ cytotoxic T lymphocytes (CTL) are immune cells known to kill cancerous and virus-infected cells and are being used to treat forms of these diseases. Both cell types are used or have been proposed for use in adoptive immunotherapy against multiple cancers following ex vivo expansion of mature or chimaeric-antigen receptor engineered effectors, with NK cells also allowing for re-targeting using monoclonal, bispecific and trispecific antibodies [1]. One shortfall limiting application remains the failure of infused cells to expand and persist in vivo. This study aims to generate new understanding and reagents that will enable the expansion of highly functional NK cells and CTL for immunotherapy. We will achieve this by studying the capacity of genes encoded by human cytomegalovirus (HCMV) to expand these cell types.

HCMV is unique in that it infects for life and drives the largest in vivo expansions of NK cells and CTL known to man [2]. Such cells exhibit highly cytotoxic function and a signature ’effector’ phenotype. Despite the pathogenic nature of HCMV, redirection of such CMV-induced immune responses have cured or prevented infection of the animal equivalents of HIV and tuberculosis respectively [3,4], thus attenuated forms of HCMV are being investigated as novel vaccine vectors in humans. Our laboratories have developed unique reagents and state-of-the-art proteomic, virological, immunological and molecular biological techniques to study the impact of HCMV genes on immune function [5-7]. Preliminary work has identified HCMV gene families that alter the phenotype of responding NK cells and CTL. We will use these cutting edge approaches and samples from healthy individuals and cancer patients to define the underlying molecular mechanisms that drive differentiation of NK cells and CTL towards different phenotypes and functions in response to this virus. This will aid in our understanding of how to generate immune cells to protect at-risk individuals from HCMV, and also help inform the development of safe and effective HCMV-based vaccine vectors to counter different cancers and pathogens.

Funding Notes

The studentship is generously funded by the School of Medicine
Full UK/EU tuition fees
Doctoral stipend matching UK Research Council National Minimum
Additional funding is available over the course of the programme and will cover costs such as research consumables and training.
Applicants should possess a minimum of an upper second class Honours degree, master's degree, or equivalent in a relevant subject.
Applicants whose first language is not English are normally expected to meet the minimum University requirements (e.g. 6.5 IELTS)

References

In order to be considered you must submit a formal application via Cardiff University’s online application service. (To access the system click 'Apply Online' at the bottom of this advert)
There is a box at the top right of the page labelled ‘Apply’, please ensure you select the correct ‘Qualification’ (Doctor of Philosophy), the correct ‘Mode of Study’ (Full Time) and the correct ‘Start Date’ (October 2019). This will take you to the application portal.
Candidates are only permitted to submit one application but may select a maximum of three projects, ranked in order of preference in the ‘Research Proposal’ section of the application. In order to be considered candidates must submit the following information:

• Supporting statement
• CV
• Qualification certificates
• References x 2
• Proof of English language (if applicable)

Related Subjects

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