Communal coordination of cell behaviour underpinning organ formation
Research in my lab aims to address the fundamental question of “how do cells work together to collectively build complex tissues?”. In particular, how are groups of cells able to interpret a signal, accurately communicate this information to neighbouring cells and precisely coordinate their communal cell behaviour, morphology and identity to drive functional organ formation?
This question is core to understanding how all tissues form during embryonic development via the process of “morphogenesis” – whereby un-patterned cell populations elegantly reorganise into distinct organs and tissues. Moreover, such communal coordination of cell behaviour also critically underpins the repair or regeneration of tissues following damage, and these processes are frequently subverted in disease. As such, the ultimate aim of our work is to exploit knowledge of these mechanisms to realise novel therapeutic strategies tackling pathological tissue formation and/or repair in disease states as diverse as myocardial infarction, chronic wounds and cancer.
To tackle these questions, we focus on the vertebrate cardiovascular system and formation of the intricate blood vessel network that supplies all tissues with essential oxygen and nutrients. Blood vessel formation (or angiogenesis) is a paradigm model for investigating the core mechanisms by which cells communally coordinate their behaviour during tissue formation; including broadly conserved processes such as collective cell migration, competitive cell fate decisions, tissue branching morphogenesis, tissue patterning/guidance mechanisms and tubulogenesis. Moreover, dysregulation of angiogenesis underpins numerous pathological processes, including tumour growth and metastasis, retinopathy and blindness, arthritis, limb ischemia and atherosclerosis. Hence, not only do studies of angiogenesis shed light on the fundamental principles of tissue building, novel insights have clear therapeutic potential.
To define the core molecular and cellular mechanisms coordinating cell behaviour in angiogenesis, my lab adopts an interdisciplinary multiscale approach integrating genetic studies (e.g. CRIPSR gene editing and/or transgenic tools) in vertebrate models (e.g. zebrafish embryos) and primary human cells with single cell-resolution in-vivo time-lapse microscopy, ‘Omics’ techniques (e.g. transcriptomics, proteomics) and computational modelling. In recent years we’ve exploited these approaches to reveal unexpected roles for cell division (Costa et. al., 2016. Nat. Cell Biol.), signal-induced positive-feedback (Page. et. al., 2019. Cell Rep.) and spatial compartmentalisation of mRNAs (Costa et. al., 2019. bioRxiv) in the communal coordination of cell interactions and behaviour driving angiogenesis and tissue formation.