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 cell maintenance. In vivo, Wnt proteins are often secreted locally and presented to only one side of the responsive cell.
Our lab has 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 the mitochondrial content and structure is different between both daughter cells. The aim of the proposed project is to dissect the mitochondrial inheritance and bioenergetics of Wnt-mediated ACD. To that end the Research Associate (RA) will apply principles from biochemistry, and stem cell biology in conjunction with advanced imaging techniques to further probe this biological phenomenon. Specifically, the RA will use real-time 3D microscopy to follow the dynamics of mitochondria in ACD. They will focus on the link between mitochondrial inheritance, cell fate choice and components of the Wnt pathway that have been proposed to be involved in regulating the orientation of microtubules.
The successful candidate is expected to:
1) Have a good knowledge in mitochondrial structure and function and cell bioenergetics.
2) Expertise in cell live imaging and advanced image analysis.
3) Excellent skills in culturing mammalian stem cells.
How to apply: In addition to your application, please submit your CV (maximum three sides of A4) and a covering