The Role of Primary Cilium in Asymmetric Stem Cell Division
Stem cells are one of the fundamental underpinnings of tissue biology. They allow myriad tissues to be replenished by fresh cells throughout life. To preserve the regenerative capacity of the tissue, it is essential to maintain the number of stem cells. One mechanism that balances both tasks is asymmetric cell division (ACD).
In ACD, each stem cell divides to generate one daughter with a stem-cell fate (self-renewal) and one daughter that differentiates. Wnt signals are key proteins that regulate stem cells maintenance. In vivo, Wnt proteins are often secreted locally and presented to only one side of the responsive cell. Our lab has recently succeeded in covalently immobilising biologically active Wnt proteins to beads, thus revolutionising the process of specifically targeting Wnt proteins to individual cells and tissues.
By using this novel tool and advanced live imaging, we showed that Wnt-beads can induce oriented ACD of embryonic stem cells (ESCs). Accordingly, ACD produces one Wnt-proximal ESC and one Wnt-distal epiblast-like stem cell (for more details see Habib et al 2013 Science Mar 22;339(6126):1445-8 and visit our website: www.habiblab.org). Preliminary data from our lab show that localised Wnt signals regulate the orientation of the primary cilium.
The aim of the proposed project is to dissect the inheritance of the primary cilia and the role in Wnt-mediated ACD. To that end the student will apply principles from biochemistry, and stem cell biology in conjunction with advanced imaging techniques to further probe this biological phenomenon. Specifically, the student will use real-time 3D super-resolution microscopy to follow the dynamics of primary cilium in ACD. They will focus on the link between primary cilium’s inheritance, cell fate choice and components of the Wnt pathway that have been proposed to be involved in the organisation of microtubules. The applicant must have previous research experience (masters degree or equivalent).
£15,836 for 2016-17, will follow the relevant Research Council UK levels for the next 3 years
To apply, please submit your CV (maximum two sides of A4) and covering letter to [email protected] In your covering letter (maximum one side of A4), please summarise your previous research experience and explain why you are interested in our lab. Please also write a brief preliminary proposal (one side of A4) of experiments that you think will be suitable for this project. Please note that applications submitted without a proposal will not be considered.