We have utilised Drosophila as a model system to identify novel and conserved genes essential for progression through the cell cycle and normal cellular physiology. From our analyses of mutations that gave rise to abnormally-condensed chromosomes, we identified Invadolysin – a zinc-metalloprotease that we have shown to link cell division and cell migration in D. melanogaster (McHugh et al., 2004). Invadolysin localises to lipid droplets in mammalian cell lines, and Drosophila invadolysin mutants have a decreased triglyceride:protein ratio (Cobbe et al., 2009). Invadolysin additionally interacts with mitochondrial ATP synthase subunits (Di Cara et al., 2013) and plays a role in angiogenesis (Vass and Heck, 2013). As many proteases function in catalytic pathways, it is intriguing that the first genetic interactor of invadolysin is a ubiquitin protease (nonstop) – targeting histone H2B, and thereby linking to the chromosome defects we observed initially (Gururaja Rao et al., 2015). Interestingly, mono-ubiquitinated H2B was elevated in both invadolysin and nonstop mutants – but localized surprisingly to the cytoplasm. Invadolysin also plays a role in insulin signaling and adipogenesis – in the fly and in vertebrate in vitro models (Chang et al., 2016). We have recently discovered that a secreted form of invadolysin is present in vertebrate serum and invertebrate hemolymph. As the gene is essential for life, we hypothesise that the secreted form of invadolysin may be playing a role crucial to normal physiology, and possibly serve as a biomarker for certain human disease states. To examine the role(s) of circulating invadolysin, we are examining extracellular matrix components. Using fluorescent probes, we are able to detect differences in the extracellular matrix comparing wild type and mutant animals. We plan to expand these experiments with the identification and analysis of additional proteases in Drosophila that may also impact upon the dynamics of the extracellular matrix.