Switching off immunity in health and disease

Project description

Immune activation, for example during an infection, is followed by feedback inhibition which dampens down the response. A failure to activate immunity results in overwhelming infection; equally, an inability to halt the immune response results in pathological inflammation and sometimes autoimmunity. We are interested in the molecular mechanisms used by the immune system to halt the response. In particular, we are interested in the action of immunosuppressive cytokines (such as TGF-beta and IL-10) and how anti-inflammatory drugs (such as steroids) mimic the action of these cytokines.

The project will use molecular and cellular techniques to define the signalling pathways used by immunosuppressive molecules to regulate immunity and how these pathways are modulated in human cancer and inflammation. The project will focus on the action of inhibitory molecules on natural killer (NK) cells and cytotoxic T cells, comparing cytokines and drugs for their ability to regulate immune activity. Tumours often exploit these pathways to inhibit anti-tumour immunity.  Defining the mechanisms operating in cancer will enable the design of therapeutic strategies that will help to restore anti-tumor immunity.

1. Holmes TD, Wilson EB, Black EVI, Benest AV, Vaz C, Tan B, Tanavde VM, Cook GP (2014) Licensed human natural killer cells aid dendritic cell maturation via TNFSF14/LIGHT. Proc Natl Acad Sci USA 111(52):E5688-96.

2. Brownlie RJ, Garcia C, Ravasz M, Zehn D, Salmond RJ, Zamoyska R. 2017. Resistance to TGFβ suppression and improved anti-tumor responses in CD8+ T cells lacking PTPN22. Nat. Commun. 8(1):1343.

3. Wilson EB, El-Jawhari JJ, Neilson AL, Hall GD, Melcher AA, Meade JL and Cook GP (2011) Human tumour immune evasion via TGF-b blocks NK cell activation but not survival allowing therapeutic restoration of anti-tumour activity. PLoS One 6:e22842.

Entry requirements

This project is available immediately to both Home/EU rate applicants and International applicants who are able to self-fund their studies. Students must be able to provide the appropriate level of fees based on their fee status plus laboratory consumables costs per year. This is in addition to the provision of personal living expenses.

The project is suitable for students with a strong background and interest in immunology, biochemistry/molecular biology and cancer research.

You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject.

Candidates 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:

• 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.

Applicants with sufficient funding must still undergo formal interview prior to acceptance in order to demonstrate scientific aptitude and English language capability.

How to apply

Applications can be made at any time. Potential applicants are welcome to contact Professor Graham Cook with informal enquiries about this research project.

To formally apply for this project 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. 

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly by school. 

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 to inform us you would like to be considered for this scholarship project.