The Francis Crick Institute
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.
The Research Group
The Developmental Signalling Laboratory headed by Caroline Hill focuses on cell signalling in early vertebrate development and disease – see . 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:
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
- Good knowledge and hands on experience of working with embryonic stem cells
- Technical expertise in differentiating embryonic stem cells to different tissue types
- Technical expertise in live imaging
- Track record of writing papers as evidenced by publications or submitted manuscripts in referred journals
- Evidence of data presentation at scientific meetings
- Strong organisational skills and thorough record-keeping
- Ability to work independently and also in a team
Desirable
- Experience in signal transduction research
- Experience in ‘omics techniques and bioinformatic analysis
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.
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