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MRC Toxicology Unit

 

All applications should be submitted via the University's online applicant portal.

 

We are currently accepting applications for the following PhD Studentships:

 

Project Title: Toxicity-induced phase separation of transcriptional regulators: mechanisms and cellular consequences   
Supervisor: Dr Ritwick Sawarkar
Closing Date: 10th February 2020
Project Outline
We have recently observed that proteotoxicity in human cells causes biomolecular condensation of critical transcriptional regulators leading to global transcriptional changes. We do not understand the mechanisms underlying the formation of these nuclear condensates or their function in response to toxic injury. The project combines molecular cell biology with biochemistry as well as functional genomics to identify cellular factors that link toxic injury to nuclear condensates.
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Project Title: Single Cell assessment of adaptive immune clonal expansion and differentiation in responding to immune checkpoint blockade.   
Supervisor: Dr James Thaventhiran
Closing Date: 10th February 2020
Project Outline:
Immune checkpoint immunotherapy triggers adaptive immune lymphocyte activation that can lead to effective treatment for cancer. Adaptive immune lymphocyte activation can also lead to autoimmunity—the chief toxicity of this treatment. Mechanistic studies into the efficacy of this modality has been hampered by our ability to clonally track adaptive immune cells that respond to immunotherapy. The Thaventhiran group have validated a unique preclinical system that can clonally track adaptive immune lymphocytes responding to diverse triggers. They are currently using this system with CITE-seq and single-cell RNA sequencing to study the clonal response to melanoma.
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Project Title: Regulation of protein synthesis by elongation control following toxic injury  
Supervisor: Professor Anne Willis
Closing Date: 10th February 2020
Project Outline:
Regulation of protein synthesis makes a major contribution to post-transcriptional control pathways.  Under cell stress resulting from exposure to a wide range of agents from environmental e.g. UVB light, to treatment therapeutically relevant chemicals such as doxorubicin or platinum-based compounds, post-transcriptional programmes are initiated to orchestrate the appropriate cellular response.  Recent data suggest that the elongation stage of protein synthesis is a central regulatory node for translational control and data from our laboratory with our collaboration,  has shown that message specific, elongation control is central following oxidative stress1 and for disease mechanisms in both tumorigenesis 2 and neurodegeneration3,4.
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Project Title: Exploring The Therapeutic Window of CAR-T Cell Therapy
Supervisor:  Dr Mike Chapman       
Closing Date: 10th February 2020
Project Outline:
Immunotherapy, including chimeric antigen receptor-T cells (CAR-T cells) and checkpoint inhibition, is a powerful new class of cancer treatment. However, it is often beset by severe and life-threatening toxicity. This toxicity is challenging as it is driven by the same mechanisms that target the tumour cells. Understanding the differences between the pathways that mediate cancer cell killing and those that cause toxicity will be crucial to refine these treatments so that they are safer and more effective. This project will study samples from patients undergoing immunotherapy and develop in vitro and computational models to better elucidate the pathways involved. Successful models will be advanced to in vivo testing.
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