Abstract

Multidrug efflux systems are ubiquitously expressed in prokaryotic and eukaryotic organisms. They play critical roles in multidrug resistance in cancer and infectious disease and provide an important barrier system for xenobiotics. A delicate balance exists between the efflux of xenobiotics and signaling molecules needed for maintenance of human health and protection from toxic substances, and the effective exposure of both the human host and microbes to pharmacologic interventions. This is of particular relevance for global health concerns ranging from infectious diseases in developing and developed countries, to the opiod crisis across the world and the increasing burden of neurodegeneration and chronic diseases related with cellular transport and communication that accompanies longer lifespans. This conference will include presentations on key developments across a broad spectrum of topics covering the multiple roles of efflux transporter pumps in health and disease. The impact of the explosion of structural data from cryo-EM on our molecular understanding of the substrate selectivity and regulation of the transport of molecules across cell membranes will be highlighted. Speakers will discuss the role of multidrug efflux pumps as barriers to harmful xenobiotics, including roles in protecting the CNS, the fetus and the reproductive organs. The program will also include talks on the interrelatedness between pharmacological targeting of efflux pumps and systemic toxicity and key strategies for CNS penetration for the treatment of neurodegeneration and other neurological disorders in the scope of aging-related diseases. A discussion of how microbial strategies for drug resistance can be harnessed for reversing the current crises in the treatment of malaria, multidrug extensively resistant tuberculosis and multidrug resistance in Gram positive and Gram negative bacteria is planned. How the antimicrobial war can be supported by a healthy microbiome and the importance of transport and signaling among biofilms will also be subject of intense debate. Overall, this conference will foster discussion at the frontiers of science in multi-drug efflux systems for advancing global health and the UN Sustainable Development Goals envisaging a world with equitable and universal access to quality education and health care, where physical, mental and social well-being are assured. This GRC will also be held in conjunction with the Gordon Research Seminar for young scientists (April 27-28).