OCEANCHARCOT · Research of new marine inhibitors targeted against desease-relevant proteins kinases

Project OCEANCHArCoT – OCEAN CHemodiversity Against Cell cycle Targets.Protein Kinases (PKs) are involved in various human pathologies such as cancer, neurodegenerative diseases or can be targeted to alter the life cycle of various parasites such as those responsible neglected parasitic diseases such as leishmaniasis and malaria. There are no physiological events not involving significant changes in protein phosphorylation. Therefore, PKs constitute currently the first class of targets used by pharmaceutical companies for the characterization of novel bioactive compounds. In a project intended to exploit the ocean biodiversity, Jean-Baptiste Charcot (1867-1936), a pioneer in oceanography established large collections of marine organisms. Taking this one step further, my project aims to source marine crude extracts from the Nature Bank collection (Queensland, Australia), and from the unique Roscoff Culture Collection of microalgae (France) to identify new PK inhibitors. We will focus our analysis on PKs involved in the control of the cell division cycle (CDKs, TLKs and mitotic kinases such as Haspin and Auroras). The cellular effect of the selected inhibitors will be analysed on various cancer cell lines. This project will benefit from a new cutting edge technology will be used for the early screening of marine chemodiversity: bioaffinity (focused on PKs) mass spectrometry with a Bruker SolariX 12 Tesla FTMS. The lead-like enhanced fractions will be tested against various disease models and dereplicated in order to quickly identify bioactive molecules. Hit fractions will be produced in larger quantity before purification, characterization and pharmacological evaluation. In conclusion, OCEANCHArCoT will contribute, from Australia to France, to the research of marine bioactives to discover new therapeutic avenues to fight growing medical and social burdens such as cancer and Alzheimer’s disease.