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Postdoctoral Researcher in RNA Translation and Anti-Cancer Immunity

University of Oxford - Nuffield Department of Surgical Sciences

Location: Oxford
Salary: £38,674 to £46,913 7
Hours: Full Time
Contract Type: Fixed-Term/Contract
Placed On: 5th December 2024
Closes: 10th January 2025
Job Ref: 176916

Location: Radiation Research Institute/ORCRB

Contract type: Fixed term for 24 months in the first instance

About the role and project

Prostate cancer (PC) is the most common male cancer in the UK and more effective treatments are needed to control the late-stage disease. In the lethal disease, termed castration-resistant PC (CRPC), cancer cells sustain the pro-proliferative gene expression program despite the presence of anti-androgens by activating other oncogenes, particularly the MYC transcription factor. This gene expression program is ultimately dependent on cyclin-dependent kinase 9 (CDK9), and CDK9 inhibitors are currently in clinical trials for solid tumors. All cells depend on CDK9 to sustain gene expression, and it has not been comprehensively established why cancer cells are sensitive against the CDK9 targeting drugs.

In this project, we have two independent aims:

1) Remodelling of the translation landscape in response to CDK9 inhibition

2) Organoid tissue culture with the patient’s own immune cells

We will rely on nascent profiling of ribosome and patient-derived models to establish how CDK9 inhibition remodels the proteome and the transcriptional activity in cancer and immune cells. Using nascent Ribo-seq, nascent chain proteomics and total proteomics, we will describe how CDK9 inhibition changes PC cells ability to maintain homeostasis of the proteome. We will treat patient-derived organoids cultured in the presence of the matched peripheral blood mononuclear cells with CDK9 inhibitors and perform scSLAM-seq to establish how depletion of the major transcriptional kinase alters tumor and immune cells’ transcriptomes. These experiments are innovative but rely on the core expertise of our laboratories.

We are looking for an enthusiastic postdoctoral researcher who will be involved in every aspect of the project taking on responsibility for setting up and applying the necessary molecular biology tools. The expertise in the wet lab execution of Ribo-seq and proteomics is a significant asset for the position. The experiments will be performed in cell line models and organoids. The appointee will be expected to work closely with a number of collaborating groups in UK and in Finland/Norway. The appointee will be based principally in Oxford.

About you

You will hold a PhD/DPhil in molecular biology, oncology, immunology, or a related biomedical science field. Previous research experience and specialist knowledge in cancer immunology, RNA translation, or ribosome-profiling would be desirable. You will be experienced in cellular and molecular biology techniques with mammalian cell culture. You will have excellent verbal and written communication skills, and ability to communicate results clearly in presentations, manuscripts, and grant reports.

This full-time position is available for a 24-month period in the first instance.

Application Process

If you would like to discuss this role, please contact Professor Ian Mills: ian.mills@nds.ox.ac.uk and Dr Harri Itkonen: harri.itkonen@helsinki.fi

Applications for this vacancy are to be made online via the ‘Apply’ button above.

You will be required to upload a supporting statement setting out how you meet the selection criteria, curriculum vitae that includes potential peer reviewed publications, and the names and contact details of two referees as part of your application. Please quote reference NDSA951 on all correspondence.

Only applications received before noon on the 10 January 2025 can be considered.

Interviews will be held week commencing 22 January 2025.

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