Final Report Summary - TRANSCLCONDREG (Arylpyrrole-based Transmembrane Transporters for Induced Chloride Regulation in Cystic Fibrosis Epithelial Cells) Cells in the human body spend a lot of energy to maintain a stable concentration of ions within their cell membranes. Disruption of this delicate balance can trigger cells to initiate apoptosis, a mechanism the body uses to rid itself of damaged or dangerous cells. Unfortunately, when a cell becomes cancerous, it often changes the way it transports ions across its cell membrane in a way that blocks apoptosis. Synthetic ion transporters have been investigated before for their potential to initiate apoptosis, but this is the first time it has been demonstrated how an influx of salt into a cell (both healthy and cancerous) triggers apoptosis, known as programmed cell death. Hence, ion transporters, as was described in the renowned journal Nature Chemistry, could point the way to new anticancer drugs. This deeper understanding of the mechanisms involved resulted from a close collaboration between the University of Southampton (United Kingdom), the University of Texas (United States of America) and the Korea research center of bioscience and biotechnology (South Korea). Moreover, from this new insight into this novel trigger to initiate apoptosis, an lead compound for the development of a potent drug molecule was synthesized and shown to have promising activity and selectivity towards breast cancer cells, holding great promise in the development of new anticancer agents. A 4 fold selectivity towards cancerous over healthy cells was observed, which is expected to rise as research continuous. With assistance of the University of Southampton the appropriate handling of intellectual property rights management and commercialization is assured.The Marie Curie grant, kindly provided by the European Commission, allowed for a smooth re-integration within the European scientific community after a stay of 2 years in Japan, supported by a JSPS (Japan Society for the Promotion of Science) grant. Further, it provided the opportunity to explore the possibilities of independent research, the development of own ideas, but also the duties that go alongside this, while receiving tremendous support by a wide background of knowledge within the research group and the general society at University of Southampton. Moreover, multi-project management skills are developed supervising students opening opportunities to lead an own research team in the future.After 1.5 years of extensive research, interesting discoveries and exploration of the opportunities within the scientific society, a strong offer from industry came my way providing an opportunity to apply the acquired project management skills and scientific knowledge in a novel framework. This new challenge opened novel possibilities towards further personal development and new career steps. Moreover, this job opportunity allowed for my family and me to be together again, after living in different countries for several years. This all together made my the choose to apply for early termination, even though several interesting discoveries were made with great potential for future exploration, the right choose for me.In conclusion, this research has shown that chloride transporters can collaborate with sodium channels in cell membranes to cause an influx of salt into a cell, hence initiating programmed cell death. A novel readily obtainable molecule was found which applies this salt influx mechanism targeting breast cancer cells; a new victory in the quest to eradicate cancer, one of the most threatening diseases humanity has faced over the last decennia. This research was made possible thanks to a Marie Curie Career Integration Grant from the European Commission.
