Postdoctoral Scientist

Duration: 3 years fixed term (in the first instance) extended up to a total of 6 years, subject to successful reviews at Year 3 and 5.

About the role:

We are recruiting an experienced and highly motivated post-doctoral scientist to study brain metastasis tropism and mechanisms within the SCLC Biology Group jointly led by Prof Caroline Dive CBE and Dr Kathryn Simpson. This aggressive and highly metastatic neuroendocrine (NE) cancer has a poor prognosis with

About you:

You will be an experienced postdoc, who is looking to develop your independent ideas for project direction and delivery and will enjoy co-supporting earlier career researchers in our vibrant SCLC Biology Group. You will have a PhD in cancer biology, molecular and/or cell biology, molecular pharmacology, or a related discipline, along with significant relevant postdoctoral experience. You will be highly motivated, proactive problem solver who relishes a challenge. Prior experience in metastasis and/or lung cancer research would be beneficial.

Background:

Our research is underpinned by >65 comprehensively characterised Circulating Tumour Cell (CTC) patient derived explant models (CDX)1,2. CDX can be grown in vivo and as short-term cultures ex vivo, allowing genetic manipulation and function testing studies3. CDX recapitulate the genetic and molecular heterogeneity of SCLC and when implanted subcutaneously or intrathoracically, multiple CDX metastasise to secondary sites observed in patients including lung, liver and brain2. Our CDX studies are complemented by SCLC genetically engineered mouse models (GEMMs) and ongoing access to clinical samples with our long-term collaborator and Thoracic Oncologist at the Christie NHS Foundation Trust, Prof Fiona Blackhall, MD, PhD.

SCLC is one of the most metastatic human cancers4; ~25% of patients are diagnosed with unresectable, incurable brain metastases increasing to ~80% during disease progression5,6. SCLC metastasis, particularly brain metastasis, has been understudied due to lack of patient samples and (until now) patient-derived preclinical models. Through our CDX models where brain metastasis is routinely observed, the post holder will have a unique opportunity to study SCLC brain metastasis which does not reliably occur in other SCLC preclinical models. Through a long-standing collaboration with Prof. Greg Hannon at the CRUK Cambridge Institute the post-holder will utilise WILDseq7 to track clonal dynamics accompanied by single-cell RNAseq to understand plasticity of SCLC CDX tumours throughout the metastatic cascade, leading to target identification and biomarker discovery. Candidate molecular regulators of tropism and metastasis will be validated in patient samples. This project also benefits from strong collaborative links with neurosurgeons and the alingment between the SCLC Biology Group and the CRUK National Biomarker Centre directed by Caroline Dive. The successful applicant will become a member of the CRUK Lung Cancer Centre of Excellence co-led by Caroline Dive and Charles Swanton.

¹Hodgkinson et al., Nature Medicine (2014); ²Simpson et al., Nature Cancer (2020); ³Lallo et al., Clin Cancer Research (2018); ⁴Nakazawa et al., Oncol Lett (2012);⁵Cagney et al., Neuro Oncol (2017);⁶Ko et al., EMBO Mol Med (2020); ⁷Wild et al., eLife (2022).

Why choose the CRUK Manchester Institute?

The Cancer Research UK Manchester Institute (www.cruk.manchester.ac.uk), an Institute of The University of Manchester (www.manchester.ac.uk), is a world-leading centre for excellence in cancer research.  The Institute is core funded by Cancer Research UK (www.cancerresearchuk.org), the largest independent cancer research organisation in the world.  In spring 2023 the Institute moved into the new Paterson Building, a £150 million flagship purpose-built biomedical research centre directly attached to The Christie NHS Foundation Trust (www.christie.nhs.uk), in South Manchester.

We are partnered with The Christie NHS Foundation Trust, one of the largest cancer treatment centres in Europe.  These factors combine to provide an exceptional environment in which to pursue basic, translational and clinical research programmes.

How to apply?

To apply for this position please visit our website:  https://www.cruk.manchester.ac.uk/recruitment/candidate/searchvacancies

Informal enquiries should be directed to Professor Caroline Dive via email: Caroline.Dive@cruk.manchester.ac.uk or to Dr Kathryn Simpson via email: Kathryn.Simpson@cruk.manchester.ac.uk

Closing date: Sunday 3rd November 2024 at 11.59pm.

Interviews scheduled for: Friday 18 November 2024.