Postdoctoral Fellow – Li lab

Description

Postdoctoral Fellow

Job title: Postdoctoral Fellow – Vivian Li lab

Reporting to: Vivian Li, Senior Group Leader and Assistant Research Director at the Francis Crick Institute and Thomas Sheahan, Senior Research Scientist of Target validation team in Oncology AstraZeneca 

Contact term: This is a full-time, fixed term 3-year position on Crick terms and conditions of employment with potential for extension.

Salary for this Role: From £43,210 with benefits, subject to skills and experience

The Research Group

This is a joint collaborative project between Vivian Li Laboratory at the Francis Crick Institute and Thomas Sheahan from Oncology AstraZeneca. This is a full-time position at the Crick and is expected to be based at the Crick with occasional collaborative visit at AZ.

Dr Li’s laboratory investigates the molecular regulation of intestinal stem cell and cancer, focusing on WNT signalling, a molecular pathway contributing to virtually every developmental decision in the lifetime of an organism and is hyperactivated in nearly all colorectal cancer (CRC) to promote cancer cell growth. Despite decades of research, WNT pathway is considered as undruggable in cancer due to its pivotal role in many body systems (Novellasdemunt et al, 2015). The overarching aim of our lab is to find new druggable targets against WNT signalling to improve CRC treatment through investigating both cell intrinsic and extrinsic role of WNT in tumour development. Research techniques used in the laboratory include high-throughput multi-omics, “mini-guts” and transgenic mouse models. The mini-guts, also called organoids, are powerful research tools that allow us to model human organs and diseases in a dish (Corrò et al, 2020). The Li lab has pioneered the use of patient-derived organoids for regenerative medicine and disease modelling by developing innovative intestinal tissue engineering technology (Meran et al, 2020). Details of research projects currently being undertaken can be seen at: .

Dr Sheahan is a senior research scientist in the Target Validation team within AstraZeneca’s Oncology Bioscience department. The team plays a key role in identifying and validating future cancer targets across tumour types, including in the key strategic area of CRC, utilizing techniques including interactomics to aid in target discovery. We make extensive use of in vitro models across a range of cancer types to understand the phenotypes of putative drug targets, to characterize targets mechanistically, and to explore possible drug modality approaches. The Target Validation team is embedded within the wider AstraZeneca Oncology community, allowing access to an experienced and supportive drug discovery network.

The Project

Colorectal cancer (CRC) represents a disease area of significant unmet clinical need, comprising a population of 150,000 new patients/year in the US and remaining the second largest cause of cancer deaths. Currently, there is a lack of effective targeted treatments. The Wnt/beta-catenin (CTNNB1) pathway is the most frequently mutated in CRC, with mutations in the APC subunit of the CTNNB1 destruction complex identified in > 75% of patients. There is therefore an urgent need for treatments targeting the CTNNB1 pathway in CRC. However, CTNNB1 itself is required for normal intestinal homeostasis and previous attempts to target the pathway have failed due to unacceptable toxicity. Novel approaches are therefore needed to identify components of the CTNNB1 pathway that are required in tumours but are not essential for normal gut function. 

The purpose of this role is to screen for tumour-specific Wnt drug targets by exploring differential CTNNB1 transcriptional interactomes using unbiased proteomics approaches. We aim to identify unique co-regulators that interact with CTNNB1 differentially in Wnt-activated cancer, which could represent tumour-specific targets in CRC that are not required for normal gut function

In this project, some of the specific techniques include but are not limited to:

3D organoid culture derived from primary human and mouse intestine

RIME (Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins)

ChIP-Seq (Chromatin Immunoprecipitation sequencing)

ATAC-Seq (The assay for transposase-accessible chromatin with sequencing)

CRISPR-targeting

Animal handling

The postholder will be responsible for:

Liaising with collaborators to perform shared experiments

Writing and contributing to the preparation of scientific manuscripts, reports, presentations and records of experimental plans and results

Supervising and providing technical advice to more junior members of the team when appropriate

Postdoctoral Fellows will lead their own projects, contribute to other projects on a collaborative basis (both in the lab and with external collaborators) and may guide PhD students in their research. The ability to work in a team is essential.

Key experience and competencies

The post holder should embody and demonstrate our core Crick values:

Bold; Open; Collegial

Essential

PhD in Developmental Biology, Biochemistry, Tumour Biology or in the final stages of PhD submission

Good knowledge and experience in molecular biology and biochemistry

Good knowledge and experience in transcriptional regulation studies

Good proteomic skills such as immunoprecipitation and Mass Spectrometry

Experience in 3D organoid culture

Excellent track record of research as evidenced by publications in referred journals

Strong written and oral communication skills as evidenced by data presentation at scientific meetings

Ability to work independently as well as a good team player

Desirable

Experience in RIME

Experience in ChIP-seq workflow and analysis

Animal work experience

Experience in orthotopic intestinal tumour model in mice

Experience in histology and confocal imaging

About Us

At the Crick, we conduct research at the forefront of biomedical research. We combine rigour with an open and collaborative culture, and are outward-looking, reflecting our status as a partnership of six organisations aiming to pool knowledge, ideas and resources.

We have a wide research portfolio with no divisions or departments, bringing biomedical researchers together with clinicians, physical scientists and applied scientists from our pharmaceutical partners.

We aim to attract the most talented researchers and support them to tackle innovative research questions. Our science technology platforms provide our researchers with access to state-of-the-art technology and expertise.

We provide an excellent learning environment with dedicated education programmes in public engagement with science, education and personal development, and a postdoc training programme that prepares scientists for leadership roles in science.

If you are interested in applying for this role, please apply via our .

All offers of employment are subject to successful security screening and continuous eligibility to work in the United Kingdom.

If you require a visa to work in the UK we will help support your application should you be successful

Equality, Diversity & Inclusion

We welcome applications from all backgrounds. We are committed to providing equal employment opportunities, regardless of ethnicity, nationality, gender, sexual orientation, gender identity, religion, pregnancy, age, disability, or civil partnership, marital or family status. We particularly welcome applications from people who are Minority Ethnic as they are currently underrepresented in the Crick at this level.

Diversity is essential to excellence in scientific endeavour. It increases breadth and perspective, leading to more innovation and creativity. We want the Crick to be a place where everyone feels valued and where diversity is celebrated and seen as part of the foundation for our Institute’s success.

The Crick is committed to creating equality of opportunity and promoting diversity and inclusivity. We all share in the responsibility to actively promote dignity, respect, inclusivity and equal treatment and it is our aim to ensure that these principles are reflected and implemented in all strategies, policies and practices.

Read more on our website: 

Find out what benefits the Crick has to offer:

For more information on our great pay and benefits package please click here:

Equality, Diversity & Inclusion:

We welcome applications from all backgrounds. We are committed to providing equal employment opportunities, regardless of ethnicity, nationality, gender, sexual orientation, gender identity, religion, pregnancy, age, disability, or civil partnership, marital or family status. We particularly welcome applications from people who are Minority Ethnic as they are currently underrepresented in the Crick at this level.

Diversity is essential to excellence in scientific endeavour. It increases breadth and perspective, leading to more innovation and creativity. We want the Crick to be a place where everyone feels valued and where diversity is celebrated and seen as part of the foundation for our Institute’s success.

The Crick is committed to creating equality of opportunity and promoting diversity and inclusivity. We all share in the responsibility to actively promote dignity, respect, inclusivity and equal treatment and it is our aim to ensure that these principles are reflected and implemented in all strategies, policies and practices.

Read more on our website: