Postdoctoral Fellow - Cader Lab

Postdoctoral Fellow – Z Cader Lab

Reporting to: Dr Zaeem Cader, Clinician Scientist Group Leader

Contact term: This is a full-time, fixed term (4 year) position on Crick terms and conditions of employment.

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

The Research Group

The Cader lab studies the complex interplay between metabolism and immunity across every level of organismal organisation from proteins to cells to organs and the whole-body. In doing so, we wish to learn how our diet, microbiota, and other environmental factors shape our immune system in health and disease. We look to investigate the dietary and microbial metabolites our cells are exposed to, how we sense and process these, and the forms of metabolic stress that can emerge if not handled correctly. We are particularly interested in how our body stores and utilises energy to fuel immunity. Importantly, we seek to understand the consequences of metabolic dysfunction for diseases such as autoimmunity and chronic inflammation. To address these questions we embrace a broad range of experimental techniques including advanced imaging, mass spectrometry, and genetics.

The Cader lab will be starting at the Crick in December 2024.

The Project

We are seeking an enthusiastic, hard-working and conscientious Postdoctoral Fellow to join our new research team at the Francis Crick Institute. There are up to 2 open positions available. This is an exciting opportunity to pioneer cutting-edge techniques in a world-leading institute and take a leading role in an ambitious research programme studying novel disease biology.

The incidence of autoimmunity and chronic inflammatory diseases such as Crohn’s disease and rheumatoid arthritis is rising globally. Yet, we still understand very little about why individuals develop such conditions in the first place. Guided by genetic studies, our research is beginning to define the key cellular pathways responsible for these conditions. One particular success has been our discovery and characterisation of a novel enzyme strongly linked to inflammatory bowel disease and arthritis. Our work has revealed the importance of energy, metabolism and redox balance in shaping immunity. This is one of the most ancient and fundamental levels of immune regulation and how we respond to infection.

This project will follow-up and further investigate this intriguing interplay between metabolism, redox, energy homeostasis and immunity. We aim to do this across different levels of organismal organisation spanning proteomic modification to intracellular signalling to immune function in tissues of interest such as lymph nodes and the intestine. As these are dynamic and highly contextual processes, we seek to embrace state-of-the-art techniques across imaging and mass spectrometry.

There are a number of exciting lines of investigation, which would be available for the successful applicant(s) to pursue. In particular, the prospective candidate(s) would drive either of the following projects:

• During the course of their activation, immune cells require distinct metabolic states necessary for the different phases of an immune response. Our work has highlighted that these are crucial for supporting the energetic and chemical demands of immune signalling, which must respond rapidly but flexibly to changing levels of intracellular pathogenic threat. However, we still have a very nascent understanding of the dynamic coordination of intracellular metabolism and structural reorganisation required to meet these demands, following infection or other immune stimuli. Furthermore, we have identified several candidate metabolic and redox genes that are strongly implicated in immune-mediated disease, but whose function in immunity are yet to be characterised. We look to employ advanced imaging and metabolomic approaches such as super-resolution microscopy, imaging cytometry, redox proteomics, and stable-isotope flux analysis to investigate these processes in unprecedented detail with an aim to discover entirely novel immunometabolic biology.
• Metabolic coordination is even more poorly understood at a whole tissue or organ level. We are only beginning to appreciate the importance of metabolic cross-talk between cells for maintaining specialist cell function in sites such as the brain and intestine. Metabolic dysfunction underpins virtually every ‘disease of westernisation’ from diabetes to dementia. In this project, we seek to investigate cellular metabolism in vivo and study metabolic cross-talk in physiological and disease relevant states in animal models. The successful candidate will utilise orthogonal methods for tracking and functionally investigating immunometabolic processes in vivo . We are particularly interested in developing approaches for intravital imaging and/or in vivo stable isotope flux analysis. We would also be interested to hear from candidates with experience and interest in immune- and metabolic in vivo phenotyping, particularly following diet or microbiota-based intervention.

Both post-doctoral projects will harness genetic and chemical tools to manipulate and image key metabolic and redox pathways. Candidates will also be encouraged and supported to innovate new tools and methods for studying immunometabolism both in vivo and in cells through genetic engineering and chemical biology approaches. This will be combined with next-generation genome editing screens to discover entirely novel biology and new mechanisms linking metabolism and redox to immune function. Importantly, the proposed work will generate important insight into the nascent fields of immunometabolism to pave the way for better disease understanding and therapeutic strategies.

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 a relevant life science field or in the final stages of PhD submission
• Good knowledge and interest in either immunology and/or metabolism
• Extensive wet-lab experience with expertise across several relevant methods in cell biology, molecular biology, immunology or metabolism.
• Technical expertise in one or more of the following: imaging, metabolomics or animal models
• Experience of working independently, designing experiments and introducing new techniques into a lab
• Track record of writing papers as evidenced by publications or submitted manuscripts in referred journals
• Ability to work independently and be capable of interacting within a group

Desirable

• Experience in research performing either immunological assays/phenotyping or metabolomics
• Some experience performing molecular cloning, genetic modification and/or genome editing
• In vivo projects would require significant experience with animal experimentation
• Shows attention to detail with a clear focus on high quality data and documentation
• Strong team working and communication skills
• Ability to work flexibly within a team and comfortable learning new techniques
• Open, honest and respectful

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 . Informal enquiries are welcome, and should be directed to
• 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

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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.

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