Postdoctoral Fellow - Deciphering ADC target-independent toxicity mechanisms in a 3D bone marrow model

R-180200: Postdoctoral Fellow - Deciphering ADC target-independent toxicity mechanisms in a 3D bone marrow model

Based in: The Discovery Centre, Cambridge Biomedical Campus, Cambridge, UK

Competitive Salary, Bonus & Benefits Package

Do you have a background in haematopoiesis, cell biology, or pharmacology; a Scientist with a passion for mechanistic in vitro investigations? Would you like to apply your expertise to impact the field of cancer therapeutics in a company that turns ideas into life changing medicines? Then join the Oncology Safety team at AstraZeneca and unlock the power of what science can do.

About AstraZeneca

AstraZeneca is a global, science-led, patient-centred biopharmaceutical company focusing on discovering, developing, and commercialising prescription medicines for some of the world’s most serious diseases. But we’re more than a global leading pharmaceutical company. At AstraZeneca, we're dedicated to being a Great Place to Work and empowering employees to push the boundaries of science and fuel their entrepreneurial spirit.

About our Postdoc Programme

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

AstraZeneca’s Postdoc Programme is for self-motivated individuals looking to deliver exciting projects in an encouraging, engaging, and innovative environment. Working with multidisciplinary scientific teams from a diverse set of backgrounds and a world-class academic mentor specifically aligned to your project. Our postdocs are respected as specialists, encouraged to speak up, and supported to share their research at conferences, publish papers, achieve their goals.

Make a more meaningful impact in your career, with greater ownership and accountability to make a contribution whilst making a difference to the lives of our patients.

This is a 3-year programme.

About the Opportunity

The primary aim of this position is to identify and quantify the major mechanisms underlying Antibody Drug Conjugate (ADC) mediated off-target driven haematotoxicity (haemtox), using a complex, human, in vitro 3D model of bone marrow (BM) haematopoiesis.

The Oncology Safety team, part of Clinical Pharmacology and Safety Sciences, is a critical drug hunting partner within AstraZeneca, supporting all aspects of pre-clinical safety across Oncology. With a rapidly growing ADC portfolio we are actively investigating mechanisms of toxicity, and how we might mitigate them to make safer and more efficacious medicines, using pre-clinical models to quantitatively assess the risk of novel compounds. We use a variety of in vitro and in vivo bone marrow models to do this and are industry leaders in using in vitro BM microphysiological system (MPS) models for quantitative clinical predictions, particularly within the small molecule space.

Project Focus

You will be tasked with using this complex 3D BM model to interrogate ADC-mediated toxicity mechanisms, assessing multiple lineages simultaneously over time using flow cytometry. This will be supported by rescue experiments to quantify the relative contribution of each mechanism to haemtox at a systems level.

Whilst working independently on your own project, you will be using models (e.g. reagents, equipment) in active use across Oncology Safety and beyond, so a proactive and flexible mentality with strong communication skills are essential for ensure smooth operations across the group.

Your AZ supervisor will be Suzanne Randle (Associate Director, Oncology Safety), an authority on in vitro models of BM toxicity and their use in drug development. You’ll also work closely with other Oncology Safety and BM MPS team members, cross-pollinating ideas and best practise for such models in ADC development, building confidence in their use translating pre-clinical data into clinical adverse effect prediction.

Academic mentorship and guidance will be provided by John Hartley, Professor of Cancer Studies, UCL.

What You’ll Do

Our successful postdoc will work closely with Oncology Safety lab scientists to gain understanding and expertise in several in vitro BM models of varying complexity, before working independently to explore mechanisms of off-target haemtox associated with ADCs. This includes the use of long term complex 3D BM co-culture models and as such you will be responsible for establishing and maintaining sufficient cultures for your needs.

Using a variety of complementary approaches such as CRISPR, engineered ADCs, and small molecule inhibitors, you will interrogate various mechanisms of toxicity. You will also have the opportunity to work collaboratively with other functions such as Integrated Bioanalysis and Systems Modellers to fully interpret any in vitro findings in the context of clinical translation. You will be encouraged to actively engage with other BM team members as well as the wider Oncology Safety and Postdoc communities.

Key Duties & Responsibilities:

• Designing and conducting complex in vitro experiments, as well as analysing, interpreting, and presenting data within different forums
• Plan, write, publish, and present high-quality scientific papers
• Opportunity to mentor PhD students, graduate scientists, and master thesis students.

Qualification, Skills & Experience

Essential Requirements

• PhD or equivalent in cellular/molecular biology, experimental medicine, or related subject area
• Extensive experience in mammalian cell culture is essential, ideally in primary cell or complex models
• Strong planning and organisation skills with evidence of successful independent working
• High levels of motivation, creativity and problem-solving skills
• Effective oral communication and collaborative team working skills

Desirable Requirements

• Knowledge or experience in haematopoiesis or bone marrow biology, as well as flow cytometry would be advantageous
• Alternatively, extensive expertise in Antibody Drug Conjugate efficacy or safety would be beneficial
• Track record of high quality, cross collaboration peer-reviewed publications

Reasons to Apply

This postdoctoral position provides an exciting opportunity to work in the state-of-the-art Discovery Centre at AstraZeneca.

As an ambitious company aiming to be number 1 in Oncology, we are expanding our exciting portfolio of therapies to include many tumour-targeting modalities such as ADCs.

You’ll work on ground-breaking cancer therapy research, with the potential to influence ADC drug discovery and development for many years, providing an opportunity to become a leading authority in 3D in vitro bone marrow models and their use in interrogating complex cellular mechanisms.

Our postdoc will work with world leaders across safety science, cancer biology and ADC technology, as well as be supported by an expert external academic supervisor bridging the gap between industry and academia.

We expect this project to lead to high-impact publications and provide opportunities to present at leading ADC/Toxicology/Cancer conferences. As a postdoc spanning both academia and industry, the successful candidate will not only develop their academic research skills but also have the unique opportunity to gain insight into the drug discovery process, which will be of great benefit for their future career in either sector.

Why AstraZeneca

The unique positioning of this postdoc means you will be working at the cutting edge of complex in vitro bone marrow model development. Moreover, have the satisfaction of knowing that methods and techniques developed will not only be published but will also be used within AZ after the postdoc position concludes, in real-life projects - and that ultimately the work you do will directly impact patients’ lives!

As a key member of a research group and taking a leading role on a Postdoctoral project, we expect regular attendance - a minimum of 3 days per week on the AstraZeneca campus. For laboratory-based scientists, this may be higher.

Given the unique positioning of our Postdoctoral researchers, you may have an additional opportunity to spend some time with an external academic mentor. In this instance, you may be required to spend some of your time working alongside them at their facility as driven by the research project. Your flexibility to meet the needs of the research and the scope of the project is required, and we also look to support you with flexibility in accordance with our standard work policies.

Next Steps

If your passion is science and you want to be part of a team that makes a bigger impact on patients’ lives, then there’s no better place to be.

This advert will be running from Monday, 23rd October 2023, we encourage your application as soon as possible, but ahead of the scheduled closing date of Sunday, 14th January 2024. In the event, that we identify suitable candidates ahead of the scheduled closing date, we reserve the right to withdraw the vacancy earlier than published.

Find Out More

AstraZeneca – Next Generation Therapeutics: https://www.astrazeneca.com/r-d/next-generation-therapeutics/antibody-drug-conjugate.html

AZ’s Postdoc Programme: https://careers.astrazeneca.com/postdocs-astrazeneca

Life at AstraZeneca: https://careers.astrazeneca.com/life-at-astrazeneca

This is what we’re made of: https://www.youtube.com/watch?v=pmFx_jr2eFo&t=2s

AstraZeneca embraces diversity and equality of opportunity. We are committed to building an inclusive and diverse team representing all backgrounds, with as wide a range of perspectives as possible, and harnessing industry-leading skills. We believe that the more inclusive we are, the better our work will be. We welcome and consider applications to join our team from all qualified candidates, regardless of their characteristics. We follow all applicable laws and regulations on non-discrimination in employment (and recruitment), as well as work authorisation and employment eligibility verification requirements.

Date Posted

23-Oct-2023

Closing Date

13-Jan-2024

AstraZeneca embraces diversity and equality of opportunity. We are committed to building an inclusive and diverse team representing all backgrounds, with as wide a range of perspectives as possible, and harnessing industry-leading skills. We believe that the more inclusive we are, the better our work will be. We welcome and consider applications to join our team from all qualified candidates, regardless of their characteristics. We comply with all applicable laws and regulations on non-discrimination in employment (and recruitment), as well as work authorization and employment eligibility verification requirements.