In the projects outlined above we are interested in understanding the connection between the molecular make up of the cell and the phenotype and behaviour of a cell population. However, at a different level of description, cell populations have behaviours which need be described without recourse to their detailed molecular landscape. Examples are the generation of proportionate groups of cells that will build an organ and, at a more obvious level, the homeostatic maintenance of a tissue.
The homeostatic maintenance of a tissue relies on stem cells and it is our contention that there are many similarities between embryonic and adult stem cells in terms of their dynamics and of the molecular engines that drive their behaviour. It is for this reason that we are interested in studying the dynamics of ES cell populations as we believe that this provides clues for understanding certain aspects of adult stem cells. However, in a separate and parallel project we are looking at the maintenance of the adult stem cells using the midgut of Drosophila. Our work, in collaboration with Ben Simons, has shown that the homeostasis of this organ is driven not by sequences of asymmetric cell divisions, as previously thought, but by the generation of asymmetry at the level of a population of cells. Homeostasis is a quantitative property of the system tightly associated with the dynamics of self renewal and differentiation.
While it is interesting to understand how fates, as qualitative entities, are implemented, our main aim is to understand the relationship between signalling and transcription in the generation of dynamics of self renewal and differentiation in a a developing tissue, the midgut of Drosophila. We do this by using a combination of genetics, quantitative cell biology and modelling.
de Navascues, J., Perdigoto, C., Bardin, A., Martinez Arias, A. and Simons, B. (2012) Drosophila midgut homeostasis results from neutral competition between symmetrically dividing intestinal stem cells. EMBO J. 31:2473-2485.
Klein, A. and Simons, B. (2011) Universal patterns of stem cell fate in cycling adult tissues. Development 138, 3103-3111.