A postdoctoral position in the Developmental Signalling Lab, The Francis Crick Institute, London, UK

The Research Group

The Developmental Signalling Laboratory headed by Caroline Hill focuses on cell signalling in early vertebrate development and disease. Our work seeks to understand how TGF-β 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.

Click here to find out more about the Hill Lab

About the role

We are looking for a highly motivated postdoc with proven research abilities and excellent publication record to work on a project that addresses how endoderm and mesoderm progenitors are specified in early zebrafish embryos through the interplay between Nodal and FGF signalling and cell cycle dynamics.

Recent discoveries in my lab have led us to a new understanding of how combinatorial morphogen signals drive cell fate decisions during embryogenesis. We have shown that mesoderm and endoderm specification in zebrafish, which occurs in a salt and pepper pattern at the embryonic margin, requires the interplay of two signalling pathways, Nodal and Fgf/Erk. However, we have shown that the cell fates are not determined by morphogen signalling levels. Instead, 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 inhibited by Fgf/Erk signalling and cells that do not switch to the endodermal fate, differentiate to mesoderm.

The project will follow up our recent results that have shown that switching to the endoderm fate occurs during windows of Erk inactivity during mitosis and early G1 phase. These Erk inactivity windows are the result of a process we have termed mitotic erasure (see PMID 37714159) where Erk activity is extinguished just before cells enter mitosis and then is reactivated with variable kinetics as the daughter cells enter G1. The project will focus on determining the underlying mechanism of Erk mitotic erasure which we hypothesise is a widespread phenomenon as we have shown it not only occurs in zebrafish, but also in Drosophila embryos and human and mouse stem cells. We then aim to understand in more detail how it contributes to the endoderm switching and explore what other cellular processes are dependent on these variable windows of Erk inactivity.

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.

About you

You will have:

• PhD in a relevant biological science, ideally in developmental biology*
• Good knowledge and experience of working with zebrafish as a developmental system*
• Technical expertise in zebrafish embryology, live imaging and image analysis*
• Track record of writing papers as evidenced by publications or submitted manuscripts in referred journals*
• Strong evidence of data presentation at scientific meetings
• Strong organisational skills and thorough record-keeping
• Ability to work independently and also in a team
• Experience in signal transduction research (desirable)
• Experience cell cycle research (desirable)

To apply please follow this link:  https://crick.wd3.myworkdayjobs.com/en-US/External/details/Postdoctoral-Fellow_R2870-2

For more information, please contact Caroline Hill (caroline.hill@crick.ac.uk)