Download Regulation of T cell metabolism and its impact on anti

PhD in the Leeds Institute of Cancer and Pathology
Faculty of Medicine and Health
University of Leeds
Regulation of T cell metabolism and its impact on anti-tumour immunity
Supervisors: Dr Robert Salmond, Professor Graham Cook
Funding: LICAP scholarship, University of Leeds
A PhD studentship is available for UK and EU citizens only, with an expected start date of October
2017. The studentship will attract an annual tax-free stipend of £14,553 for up to 3 years, subject
to satisfactory progress and will cover the UK/EU tuition fees.
You should hold a first degree equivalent to at least a UK upper second class honours degree in a
relevant subject. The project would suit a student with a strong background and interest in
immunology, biochemistry, or cell biology.
Candidate whose first language is not English must provide evidence that their English language is
sufficient to meet the specific demands of their study, the Faculty minimum requirements are:
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British Council IELTS - score of 6.5 overall, with no element less than 6.0
TOEFL iBT - overall score of 92 with the listening and reading element no less than 21,
writing element no less than 22 and the speaking element no less than 23.
Research Project:
Cytotoxic T lymphocytes have the capability of killing tumour cells directly whilst approaches to
enhance T cell function have been shown to be of significant clinical benefit in cancer. However, in
many individuals T cell immunity to cancer is blunted as tumour-associated antigens (TAA) are often
only weakly immunogenic, whilst the tumour environment is highly suppressive, with expression of
inhibitory cytokines and low levels of key nutrients. Therefore, new approaches to T cell
immunotherapy have the potential to improve clinical outcomes for many cancer patients. Our
previous work has identified the inhibitory phosphatase PTPN22 as a key negative regulator of T cell
receptor signaling and T cell responses (1). Current work in our group is focused on testing the
hypothesis that, in the absence of PTPN22, T cells will be more efficient in their ability to target
tumour cells. This is assessed using T cells from PTPN22-deficient mice in combination with tumour
cell lines expressing defined antigens, both in vivo and in vitro.
The main aim of this fully-funded studentship is to use these models to determine the
mechanisms by which PTPN22 regulates T cell anti-tumour responses. Specific aims will be, i) to
determine how loss of PTPN22 impacts upon T cell responses under conditions of nutrient
deprivation / in presence of inhibitory factors; ii) to determine how PTPN22 regulates basic aspects
of T cell metabolism; iii) to investigate approaches to manipulate T cell metabolism to improve antitumour immunity. The project will primarily encompass cellular and molecular immunology
approaches, biochemical analyses and in vivo mouse models. The project may require the student
to gain a Home Office PIL and become competent in licensed animal procedures. These results from
these studies will inform our understanding of the basic mechanisms by which T cell anti-tumour
immunity is regulated.
1. Salmond RJ, Brownlie RJ, Morrison VL, Zamoyska R. The tyrosine phosphatase PTPN22 discriminates weak self
peptides from strong agonist TCR signals. Nature Immunology. 2014; 15 (9):875-883.
Environment:
The student will join the T Cell Signalling Group (currently comprising the PI, a post-doctoral
researcher, and part-time technician) and will be based in the University of Leeds in the Section of
Infection and Immunity at the Leeds Institute of Cancer and Pathology. Training will be provided in
the relevant technical areas. For more information about the group visit our webpage at:
http://medhealth.leeds.ac.uk/info/983/infection_and_immunity/2368/t_cell_signalling_group
How to apply:
To apply for this scholarship applicants should complete a Faculty Scholarship Application form and
send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree
certificates to the Faculty Graduate School [email protected]
We also require 2 academic references to support your application. Please ask your referees to send
these references on your behalf, directly to [email protected] by no later than Friday 2 June
2017
If you have already applied for other scholarships using the Faculty Scholarship Application form
you do not need to complete this form again. Instead you should email [email protected] to
inform us you would like to be considered for this scholarship project.
Any queries regarding the application process should be directed to [email protected]. To
discuss the project informally please contact Dr. Robert Salmond ([email protected]) with a
CV.
Closing date for this studentship is Friday 2 June 2017