Cellular Detoxification and Cytoprotection

Organisms from bacteria to humans have developed systems to protect themselves from environmental stress. A key component to many of these stress response systems is expression of transporters at the cell membrane, which actively pump toxic compounds to the extracellular environment. These detoxification systems are found in various bacteria and fungi, and also in critical human organ systems such as the blood brain barrier and lining of the digestive system. Although these transport systems often play an important role in maintining cellular health and preventing accumulation of toxic compounds, their presence can also lead to undesirable consequences for human health. Several microorganisms have developed transport systems that provide a formidable defense against our most powerful antibiotics. Expression of certain transporters poses a significant hurdle to chemotherapy and absorption of compounds in the human body. We utilize structural and functional approaches to understand the mechanism of these important transporters at the molecular level.