Postdoctoral Fellow: Epigenetic Regulation Of Drug Tolerance

Cambridge

Competitive Salary, Bonus & Benefits

Do you have expertise in, and passion for, cancer signalling and drug resistance? Would you like to apply it to make a difference to the treatment of resistant patients? Join AstraZeneca and help push the boundaries of science to deliver life-changing medicines.

About AstraZeneca:

AstraZeneca is a global, science-led, patient-centred biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines for some of the world’s most serious disease. But we’re more than one of the world’s leading pharmaceutical companies. At AstraZeneca, we ‘re dedicated to being a Great Place to Work where you are empowered to push the boundaries of science and fuel your entrepreneurial spirit. There’s no better place to make a difference to medicine, patients and society.

About the Postdoc Programme:

Bring your expertise, apply your knowledge, follow the science and make a difference.

AstraZeneca’s Postdoc Programme is for self-motivated individuals looking to tackle exciting, high impact projects in a collaborative, engaging and innovative environment. You’ll work with peers and professionals from a diverse group of backgrounds, and a world class academic mentor specifically aligned to your project. We’ll help you develop valuable networks which support your research and future career development!

AstraZeneca Postdocs are respected as specialists and encouraged to speak up. They lead ground-breaking drug discovery and development research projects. Our vibrant, multi-disciplinary scientific teams empower and support our Postdocs, and we encourage them to share their research at conferences, publish papers, achieve their goals and make a difference to our patients.

You’ll learn from industry leaders working on innovative research across our organization. Our Postdoc Training Programme will support you to develop transferrable skills from influencing others to shape the agenda, to data analysis.

About the Opportunity:

Drug tolerance is a phenotypically distinct cellular state after treatment with targeted therapies, and is thought to act as a reservoir of cells that can go on to develop resistance. Previous research has shown that drug tolerant persister cells (DTPs) undergo distinct and significant epigenetic changes. Our group has previously shown that the histone deacetylase (HDAC) inhibitor quisinostat can inhibit the function of DTPs after treatment with the 3rd generation clinical EGFR inhibitor Osimertinib (Tagrisso). The aim of this project is to identify epigenetically regulated genes that are critical to maintaining the drug-tolerant phenotype after Osimertinib treatment. Analysing RNAseq profiles of DTPs treated with HDAC inhibitors and other epigenetic drugs should uncover gene sets that are crucial for this cellular state. We will also analyse the role of key epigenetic proteins on the drug response by manipulating their expression.

In the initial stage of this project you will generate cell models that underpin the research. We plan to manipulate the expression of key epigenetic regulators (CRISPR gene knockout and overexpression) to understand their impact in drug response. We will then use these models to test the effects of this modulated on gene expression, using RNAseq and potentially ATAC-seq technology, with or without co-treatment with epigenetic inhibitors. Finally, we will use insights from our multi-omic studies to return to our cell culture models to test further hypotheses on mechanisms to inhibit or kill drug tolerant cells.

Find out more here: https://www.astrazeneca.com/our-therapy-areas/oncology/Tumour-drivers-and-resistance.html

Working under the guidance of Matthew Martin & Ricardo Miragaia at AZ, and an expert external academic collaborator, you will lead this exciting project. You’ll enjoy access to ground breaking technology and equipment, and will be encouraged to follow-up new discoveries in interesting and unexpected directions. Working side-by-side with our drug development teams, you’ll gain invaluable insight into the drug discovery process which could help accelerate your future career, whether in industry or academia.

Drug tolerance is a scientifically fascinating, emerging field of research which generates considerable interest, increasing the likelihood that novel results from this project lead to high impact publications.

Qualification, Skills & Experience

Required:

  • A PhD (or equivalent) in Molecular Biology, Experimental Medicine or related field
  • Expertise in cell culture and molecular biology techniques
  • High levels of motivation
  • Creativity in problem-solving
  • Excellent oral and written communication skills
  • Good networking, collaboration and teamworking skills
  • Track record of high quality peer-reviewed publications
  • Ability to see opportunities, learn, and apply that learning to drive innovation

Desirable:

  • Expertise in cell culture using preferably human cancer cell models
  • Experience in analysis of RNAseq and/or ATAC-seq data

This is a 3-year programme. 2 years will be a Fixed Term Contract, with a 1-year extension which will be merit based.

Ready for an exciting, rewarding challenge? Apply today!

Advert Opens: 26th October, 2021

Advert Closes: 5th December, 2021

If you require any reasonable adjustments or accommodations during your application or interview process, please let us know.

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