Postdoctoral Fellow

Postdoctoral Fellow – V Li lab

Reporting to: Vivian Li, Senior Group Leader

Contact term: This is a full-time, fixed term [4 years] position on Crick terms and conditions of employment.

The Research Group

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: https://www.crick.ac.uk/vivian-li/.

The Project

Our previous work on Wnt signalling pathway have uncovered a number of novel Wnt activating mechanisms in CRC (Novellasdemunt et al, 2017; Antas et al, 2019; Novellasdemunt et al, 2020). In particular, our discoveries on the deubiquitinating enzyme USP7 as tumour-specific drug target has brought significant impact to the therapeutic intervention of Wnt signalling in cancer (Novellasdemunt et al, 2017; Novellasdemunt et al, 2023). Besides the cell intrinsic role, we also investigate the cell extrinsic role of WNT in the tumour microenvironment. In particular, we investigate the mechanism underlying the poor response rate of immunotherapy in CRC, focusing on the WNT-mediated immune evasion in the tumour microenvironment.   

Apart from therapeutic development, early detection is another key parameter to prevent cancer progression and improve the survival rate of cancer patients. Since WNT activation/APC mutation is the earliest step of most CRC initiation, we are interested in identifying specific WNT-induced factors (e.g. metabolites, proteins and microbiome) that can be used as early diagnostic markers. We have recently performed multiomic analysis of stool samples from Apc-mutant mouse models, and have generated large datasets (metabolomics, proteomics and metagenomics) in the lab to screen for genotype-specific WNT-induced changes. The proposed project will involve integrative multiomic analysis, target validation and functional analysis, including the use of transgenic mouse models, organoid culture, imaging, primary human tissue samples, metabolomics, microbiome studies etc. The candidate will not only be involved in finding markers for CRC detection and understanding the underlying biology, but will also work closely with other colleagues in the lab and contribute to other related projects (such as immunotherapy and cancer metastasis). We are looking for outstanding ambitious cancer biologist who can process multioimic data and perform functional validation of identified targets.

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

• Integrative multi-omic analysis (including transcriptomics, metabolomics, proteomics and metagenomics)
• Animal handling
• 3D organoid culture derived from primary human and mouse intestine
• Co-culture of organoids with stromal mesenchyme/lymphocytes
• Metabolomics
• Microbiome studies

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, Imaginative, Open, Dynamic and Collegial, in addition to the following:

Essential

• PhD in Developmental Biology, Stem Cells, Cancer, Computational Biology or in the final stages of PhD submission
• Good knowledge and experience in cancer metabolism and molecular biology
• Good computational/bioinformatic skill
• Animal work experience
• 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 integrative multi-omic analysis
• Experience in microbiome studies
• Experience in creating or analysing complex transgenic mouse models
• Experience in 3D organoid culture
• 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 website.
• 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

Find out what benefits the Crick has to offer:

For more information on our great pay and benefits package please click here: https://www.crick.ac.uk/careers-and-study/life-at-the-crick/pay-and-benefits

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: https://www.crick.ac.uk/careers-and-study/life-at-the-crick/equality-diversity-and-inclusion