About the Project
The Dale lab has shown previously that the Notch signalling pathway is important for cell fate decisions in both notochord progenitors and NMPs. Recently they have uncovered a mechanism by which Notch signalling is regulated by the cell cycle, potentially linking this signalling pathway to the decisions made by notochord progenitors to self-renew or differentiate3.
This PhD project is a collaboration between the Wilson and Dale labs to investigate (1) how notochord progenitors are maintained, (2) how they, in turn, interact with NMPs to sustain axis elongation and (3) whether Notch is important for regulating notochord progenitor maintenance, differentiation, or both.
To do this, the student will analyse single cell RNA-seq data both in the public domain and generated in-house using pipelines we have adopted in the lab. We will ask how heterogeneous the notochord progenitor population is. In particular we will compare the expression of Notch pathway components with cell cycle regulators. This will give the student training in bioinformatics analysis.
The student will also carry out cell cycle analysis of notochord progenitors during mouse and chick development, using traditional tools such as BrdU labelling and ex vivo culture, combined with live cell imaging, providing training in embryology and image analysis.
To determine whether notochord progenitors maintain NMPs, we will generate NMPs in culture from mouse and/or human pluripotent stem cells. Notochord progenitors can be generated in culture from pluripotent stem cells, but to bypass a potentially inefficient process, we will also test whether a chordoma (notochord- derived) cell line can provide either structural or growth factor support for NMPs. If we find that notochord progenitor cells promote NMP maintenance, we will screen for molecules that do this by determining whether cells, matrix, conditioned media or a combination provide this support, and pairing this with a candidate approach gleaned from the original bioinformatic analysis. This will provide the student with training in mouse and human pluripotent stem cell culture and differentiation, as well as medium throughput screening techniques.
The project will be based mainly in Edinburgh at the Centre for Regenerative Medicine, with regular contact with Prof Dale and, for analysis related to chick embryos and Notch signalling
The School of Biological Sciences is committed to Equality & Diversity: https://www.ed.ac.uk/biology/equality-and-diversity
The “Institution Website” button will take you to our Online Application checklist. Complete each step and download the checklist which will provide a list of funding options and guide you through the application process.
(2) Wymeersch FJ, et al. (2019) Transcriptionally dynamic progenitor populations organised around a stable niche drive axial patterning. Development. doi: 10.1242/dev.168161.
(3) Karrieri FA et al. (2019) CDK1 and CDK2 regulate NICD1 turnover and the periodicity of the segmentation clock. Embo Rep. doi: 10.15252/embr.201846436
Based on your current searches we recommend the following search filters.
Based on your current search criteria we thought you might be interested in these.