Postdoctoral Fellow – Hill lab

Postdoctoral Fellow – Hill lab Reporting to: Caroline Hill, Head of Developmental Signalling Laboratory Contact term: This is a full-time, fixed term [4 years] position on Crick terms and conditions of employment. About Us The Francis Crick Institute is Europe’s largest biomedical research institute under one roof. Our world-class scientists and staff collaborate on vital research to help prevent, diagnose and treat illnesses such as cancer, heart disease, infectious diseases and neurodegenerative conditions. The Crick is a place for collaboration, innovation and exploration across many disciplines. A space where the brightest minds can pursue big and bold ideas and discover answers to crucial scientific questions. We support them in a dynamic environment which fosters excellence with state-of-the-art infrastructure, cutting-edge facilities, and a creative and curious culture. We’ve removed traditional boundaries of departments, divisions and disciplines and instead have an open approach that supports every researcher. This gives us the freedom to collaborate and carry out high-quality, pioneering research. Creating a space for discovery without boundaries helps us to turn our science into benefits for human health and the economy. The Research Group The Developmental Signalling Laboratory headed by Caroline Hill focuses on cell signalling in early vertebrate development and disease – see https://www.crick.ac.uk/research/a-z-researchers/researchers-d-j/caroline-hill/ . Their work seeks to understand how TGF-b family signalling pathways function normally in early vertebrate development and in adult untransformed cells, and how these signalling pathways are perturbed in disease, in particular in cancer and the Marfan-related syndromes. Work in the Hill laboratory exploits the very powerful combination of early vertebrate developmental systems (zebrafish embryos), together with a variety of model tissue culture systems (human and mouse ES cell/iPS cell models), and mouse cancer models and uses a very wide range of methodologies including developmental and cell biology, cancer biology, next generation sequencing and computational modelling. The Hill lab encourages creative and independent thinking and promotes excellent training and mentoring. The group currently comprises ten people – five postdocs, two PhD students, a clinical fellow, a master’s student and a senior laboratory research scientist. For selected recent publications see: https://pubmed.ncbi.nlm.nih.gov/37714159/ https://pubmed.ncbi.nlm.nih.gov/36473458/ https://pubmed.ncbi.nlm.nih.gov/34737283/ https://pubmed.ncbi.nlm.nih.gov/34003511/ The Project Recent work in my lab has determined that mesoderm and endoderm specification in zebrafish embryos requires the interplay of two signalling pathways, Nodal and Fgf/Erk. We have shown that the distribution of endodermal progenitors results from a stochastic process where sustained Nodal signalling provides a competency window for the switching of bipotential progenitors to an endodermal fate. Switching is apparently stochastic and is inhibited by Fgf/Erk signalling. Cells that do not switch to the endodermal fate, differentiate to mesoderm. Thus, we hypothesise that short windows of Erk inactivity govern the switching to the endodermal fate and we have shown that these occur as cells undergo mitosis as a result of a phenomenon we are calling mitotic erasure. We now want to understand whether a similar mechanism controls the cell fate decision between mesoderm and definitive endoderm in humans, and if not, how this fate decision is controlled. To undertake this work, I am looking for a highly motivated postdoc with proven research abilities and an excellent publication record. The project will make use of human embryonic stem cells (hESCs) differentiated as 2D and 3D gastruloids. We will multiplex our novel Erk biosensor with live cell fate reporters to discover whether and how Erk signalling is involved in the cell fate decision between definitive endoderm and mesoderm. Furthermore, we will use multiomics scRNA-seq and scATAC-seq methodology, as well as whole genome CRISPR screening approaches to gain unbiased new insights into the mechanisms driving the specification of the mesodermal and endodermal lineages in humans. Postdoctoral Fellows at the Crick 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; Collegial Essential PhD in a relevant biological science Excellent knowledge and demonstrable practical experience of working with embryonic stem cells Extensive technical expertise in differentiating embryonic stem cells to different tissue types as 2D and 3D gastruloids Technical expertise in advanced live imaging Technical expertise in molecular biology Excellent track record of writing papers as evidenced by publications or submitted manuscripts in referred journals Evidence of data presentation at scientific meetings as talks and posters Strong organisational skills and thorough record-keeping Ability to work independently and also in a team Desirable Experience in ‘omics techniques and bioinformatic analysis Experience in signal transduction research About Working at the Crick… Our values Everyone who works at the Crick has a valuable role to play in advancing the Crick’s mission and shaping our culture! We are bold . We make space for creative, dynamic and imaginative ideas and approaches. We’re not afraid to do things differently. We are open . We’re highly collaborative and interactive, and make sure our activities are visible to the outside world. We are collegial . We show respect for one another, work cooperatively and support the wider community. At the Francis Crick Institute, we believe that diversity and inclusion are essential to driving innovation and scientific discovery. We are committed to creating a workplace where everyone feels valued, respected, and empowered to succeed, regardless of their background, identity, or personal circumstances. We actively encourage applications from individuals of all genders, ethnicities, abilities, and experiences. We want to ensure that everyone can apply and be part of our team and you will be asked as part of the process if you wish to apply under the Disability Confident scheme. We will make reasonable adjustments if you need them. If you need assistance with applying (i.e., would like to apply by phone or post) please email: weronika.kucala@crick.ac.uk To find out more about life at the Crick click here . What will you receive? At the Francis Crick Institute, we value our team members and are proud to offer an extensive range of benefits to support their well-being and development: Visas: Applicants for this role will be eligible for sponsorship to work in the UK Generous Leave : 28 days of annual leave, plus three additional days over Christmas and bank holidays. Pension Scheme : Defined contribution pension with employer contributions of up to 16%. Health & Well-being : 24/7 GP consultation services. Occupational health services and mental health support programs. Eye care vouchers and discounted healthcare plans. Work-Life Balance : Back-up care for dependents. Childcare support allowance. Annual leave purchase options. Crick Networks offering diverse groups’ support, community and inclusive social events. Perks : Discounted gym memberships, bike-to-work scheme, and shopping discounts. Subsidised on-site restaurant and social spaces for team interaction. Development & Recognition : Comprehensive training, mentoring, and a pay structure based on skills and experience.