The Developmental Signalling Laboratory at the Francis Crick Institute, 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/ . Our 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 nine people – four postdocs, two PhD students, a clinical fellow, a masters student and a senior laboratory research scientist.
I am looking for two highly motivated postdocs with proven research abilities and excellent publication records to work on two connected projects that address the issue of how endoderm and mesoderm progenitors are specified in zebrafish and how these two lineages separate during gastrulation.
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, 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 apparently stochastic and is inhibited by Fgf/Erk signalling. Cells that do not switch to the endodermal fate, differentiate to mesoderm.
One of the projects will focus on how the embryo generates the correct numbers of endoderm progenitors, even though their initial specification results from a stochastic process. We have shown that a correction mechanism exists during gastrulation and segmentation that buffers the numbers of endoderm progenitors. We want to understand how numbers of endoderm progenitors are sensed and how the numbers of progenitors are adjusted – deciphering the mechanisms involved. The second project will focus on how the endoderm and mesodermal lineages transcriptionally and physically separate during gastrulation and will make use of multi-omics scRNA-seq/scATAC-seq and novel lineage tracing approaches.
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
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 and 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
· Experience in signal transduction research
· Experience in mechanotransduction research (project 1)
· Experience in ‘omics techniques and bioinformatic analysis (project 2)