Cohen, M., Baum, B., Miodownik, M. (2011). The importance of structured noise in the generation of self-organizing tissue patterns through contact-mediated cell-cell signalling. J R Soc Interface8(59), 787-798 doi:10.1098/rsif.2010.0488.
The shape of an animal cell is an important functional property that is determined through a dynamic interplay between intrinsic information and cues from the extracellular environment. In the Baum lab we are exploring the molecular, cellular and physical processes that give rise to the shape of isolated animal cells and cells in the context of an epithelium, and are interested in the morphological processes that go awry during cancer progression. To do so, we study developing flies, human and Drosophila cell culture systems as well as cancer patient tissue using an array of diverse techniques including classical cell biological, genetic and biochemical techniques alongside the latest high-content RNA interference (RNAi) screening, imaging, computational modeling, laser ablation, biophysical tools and micropatterning methodologies.
This research falls into three general areas, all of which focus on the cytoskeleton, the cell and its environment. First, we study how cytoskeletal organisation and dynamics are regulated to control normal and cancer cell shape, and use RNAi to identify conserved, core regulators of these processes.
Second, we investigate cell rounding in mitosis at the molecular, cellular and physical level, and how this rounding contributes to spindle assembly and faithful division of the genetic material.
Third, we use the dorsal thorax of the fly as a model system to understand the orchestrated processes by which a developing tissue becomes well-ordered and refined, through changes in cell shape, changes in cell-cell junctional dynamics and through protrusion-mediated signalling.
Overall, our aim is to build up a picture of how the dynamic behaviour of individual cells contributes to tissue form and function in normal development and cancer progression.
Long version – for the link to current interests:
Overall, we are interested in the molecular, cellular and physical processes that give animal cells and epithelia their dynamic and polarised form, and in understanding how this system of control breaks down during cancer progression. Our research breaks down into three general areas.
We use a combination of RNA interference (RNAi) screening, live-cell imaging and micropatterning to study the role and regulation of the cytoskeleton in the control of normal and cancer cell shape. Using parallel RNAi screens in fly and human cells, we have identified a conserved set of actin regulators that control animal cell shape including a number of novel players. We have also employed a combination of micropatterning and RNAi to explore cell polarization, stress fibre formation and to identify a role for microtubules in the regulation of cell length.
We are interested in mitotic cell rounding, a universal feature of mitosis in animal cells and arguably the most dramatic shape a cell will ever experience. Rounding requires profound changes in the actin cytoskeleton, in membrane trafficking and in adhesion, all of which must be tightly coordinated with spindle assembly and chromosome segregation. Having recently identified a critical role for the Ezrin-Radixin-Moesin (ERM) family proteins in mitotic rounding, cortical stiffening and spindle assembly, we are now trying to assemble a more complete picture of the molecular, cellular and physical events involved. This will help us to better understand how metastatic cancer cells are able to divide outside of their normal environment and to understand the role of mitotic cell mechanics in the generation of aneuploidy during cancer progression. We are studying these processes in the developing fly, in isolated Drosophila cells, in human cell lines and in cancer tissues.
We would like to understand the processes by which actin-dependent changes in the shape of individual epithelial cells and actin-dependent cell-cell junctional remodelling give rise to the development of a well-ordered tissue. To study the final phase of tissue refinement before an animal hatches, we use the dorsal thorax of the fly as a model system, where we can easily combine live cell imaging and genetics. In recent work, we have used this system to demonstrate a role for basal filopodia in cell-cell signalling, for actin dependent endocytosis in junctional remodelling, and for epithelial cell delamination in tissue refinement. In collaboration with computational biologists at UCL’s CoMPLEX group, we have also used modeling to help understand the biophysical contribution of various processes to tissue sculpting and patterning.
Each of these three general areas overlaps and complements the others, and our laboratory works together, as well as in numerous productive collaborations, to try to understand animal cell and tissue morphogenesis during normal development, homeostasis and cancer progression.
We are currently recruiting a post-doc to study the mechanics of cell division. If you are interested, please contact us.