Coordinated change and programmed cell death in small cell networks
Supervisor
To coordinate collective change, small cell networks read and respond to both internal and external cues. Especially during development, these decisions must be highly regulated in both space and time. Examples of spatiotemporal regulation include cell contraction leading to tissue morphogenesis, clusters of migratory cells, and group programmed cell death.
The overall goal of this project is to elucidate the molecular mechanisms underpinning coordinated cell decisions in early development. We use the rapid transfer of cytoplasm and programmed cell death of Drosophila nurse cells as our model system. Previous work has shown that these processes require a developmental signal from surrounding epithelial cells, kinase activity, and an intact actomyosin network. Of particular interest is how the primary signal(s) is amplified to regulate a collective response.
Building on preliminary data in the lab showing that cells in this network act asynchronously and that an intracellular calcium rise is required, this project aims to interrogate the mechanism coordinating the global extrusion of cytoplasm and cell death. We will use live cell imaging, genetic manipulation and mathematical modelling to test different hypotheses. Initial experiments may include targeted mutagenesis of candidate genes with CRISPR/Cas9, the visualisation of calcium and actin in genetic backgrounds and mosaic analysis of mutant nurse cells. Outcomes of this project will broadly inform our understanding of support cells in animal development and the regulation of cell networks which is implicated in pathogenesis and the design of cancer therapeutics.
For more information please visit WeilLabCambridge.com or contact Tim Weil via tw419@cam.ac.uk.
References
Imran Alsous J, et al., Dynamics of hydraulic and contractile wave-mediated fluid transport during Drosophila oogenesis. Proc Natl Acad Sci U S A. 2021;118(10).doi: 10.1073/pnas.2019749118.
Weil TT, Parton RM, and Davis I., Preparing individual Drosophila egg chambers for live imaging. J Vis Exp. 2012; (60).
Image caption: Drosophila nurse cells and oocyte, actin (orange), cytoplasm (cyan), nuclei (blue).