Targeting the Mechanisms and Regulation of Transporters for Advancing Health During a Pandemic

Multidrug efflux systems export a wide a variety of substrates from cells and consequently are capable of conferring resistance to a wide range of chemotherapeutic agents. Multidrug resistance caused by active drug efflux is one of the major clinical impediments in anti-cancer chemotherapy and treatment of infectious diseases. Multidrug exporters are ubiquitously expressed in prokaryotic and eukaryotic organisms where they regulate absorption, distribution and excretion of xenobiotics, and protect sanctuary tissues by regulating the drug permeability of the blood-brain, -placenta and -testis barriers. In addition to regulating pharmacokinetics, transporters are also major players in dictating tissue-responses to drugs, from pharmacological efficacy to toxicity. The recent threat of widespread drug-resistant bacteria raises the prospect of a world without effective new antimicrobials, where patients are left vulnerable to previously treatable infectious diseases, and where organ transplants are impossible. A more complete understanding of multidrug efflux systems, from their physiological and biochemical functions to their localization, expression, and regulation is of paramount importance for the design of more targeted and highly effective treatments with improved patient outcomes. This conference will highlight recent developments in transporter biology, in particular on the molecular basis and structural dynamics of substrate recognition and transport, the integration of new biophysical insights in our knowledge of these processes, and the establishment of predictive rules of efflux inhibition and avoidance that can aid artificial intelligence and machine learning to delineate drug efficacy and pharmacological targeting. Further emphasis will be on the regulation of efflux systems mediated by local and global regulators and the multilayered control to optimize gene expression in response to specific environmental cues. As our understanding of transporter actions advances, there is greater potential for developing more specific and potent drugs that inhibit, modulate, or evade the multifaceted efflux systems and capitalize on nanomedicines and novel drug delivery strategies.

Note: 20% of talks will be selected from poster abstracts.