Safeguarding against division-induced damage in complex tissues 

Pioneering work from myself and others has provided growing evidence that dividing cells are an underappreciated weak-point in proliferative tissues. This is because division temporary disrupts cytoskeletal structure, cell shape and adhesion, generating challenges when cells divide in multicellular contexts. Therefore, specific mechanisms are required to safeguard tissue architecture during proliferative growth, with severe consequences if these mechanisms fail. Critically, the nature of these challenges depends on the architecture and complexity of the tissue. As such, I have developed live imaging protocols to study cell division in 2 complex dynamic tissues, each with distinct architectures: 1) budding tissue growth, using the genetically tractable Drosophila air sac primordium and 2) vertebrate angiogenesis, using zebrafish intersegmental vessels. My key goals are to identify factors that play protective roles during/immediately after cell division, thereby unraveling the core mechanisms that safeguard complex tissue architectures against division-induced damage. Parallel investigations, in the above complementary systems, will determine if mechanisms are conserved across tissues and identify which architectural features are particulary susceptible to division-induced damage. Longer-term, this work will be relevant to several disease states, including the loss of tissue organisation/integrity seen during tumour initiation, cell dispersal during metastasis and vascular diseases associated with excessive division.