Cancer and extracellular vesicles
Extracellular vesicles (EV's) are released or shed by many different cell types and are capable of influencing cellular behaviour and human physiology. EV's are composed of complex signatures of lipids, small molecules, nucleic acids and proteins that synergistically elicit physiologically relevant changes in either local or distant cells, tissues and organs. Since exosomes and other classes of EV's are emerging as powerful biomarkers and as therapeutics they have an enormous potential to transform biomedicine. Metalloproteinases are dysregulated in many different cancers and have been found within extracellular vesicles
*Kelwick, R., Desanlis, I., Wheeler, G. N. & Edwards, D. R. The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family. Genome Biol. 16, 113 (2015).
*Kelwick, R. et al. Metalloproteinase-dependent and -independent processes contribute to inhibition of breast cancer cell migration, angiogenesis and liver metastasis by a disintegrin and metalloproteinase with thrombospondin motifs-15. Int. J. cancer 136, E14-26 (2015).
Wagstaff, L., Kelwick, R., Decock, J. & Edwards, D. R. The roles of ADAMTS metalloproteinases in tumorigenesis and metastasis. Front. Biosci. (Landmark Ed. 16, 1861–72 (2011).
cell-free systems and synthetic biology
Cell-free systems that are based on cellular extracts were originally developed as experimental systems to understand fundamental aspects of molecular biology, cellular biochemistry and for in vitro protein production. Synthetic biology approaches are enabling the re-purposing of cell-free systems as coupled in vitro transcription–translation characterisation platforms for the prototyping of DNA based parts, devices and systems. Cell-free transcription-translation systems have been employed to rapidly prototype DNA regulatory elements, logic systems, medical biosensor devices and biomaterials.
Kelwick, R., Ricci, L., Chee, S. M., Bell, D., Webb, A. J., and Freemont, P. S. (2018). Cell-free prototyping strategies for enhancing the sustainable production of polyhydroxyalkanoates bioplastics. Synth. Biol. 3. doi:10.1093/synbio/ysy016.
Kelwick, R., Webb, A. J., MacDonald, J. T. & Freemont, P. S. Development of a Bacillus subtilis cell-free transcription-translation system for prototyping regulatory elements. Metab. Eng. 38, 370–381 (2016).
Kelwick, R., MacDonald, J. T., Webb, A. J. & Freemont, P. Developments in the tools and methodologies of synthetic biology. Front. Bioeng. Biotechnol. 2, 60 (2014).