The ABCs of Transport
An Evolutionary War
In the battle against infectious microbes and cancer cells, each new weapon in the antibiotic or antitumor arsenal is met with ever increasing resistance. At the heart of such multidrug resistance are proteins that harvest the energy of ATP hydrolysis to pump antibiotics and anti-cancer drugs out of the targeted cells. Through genetic changes that lead to the overexpression of ABC transporters, previously sensitive cells evolve to become resistant to our best medicine.
With Atomic Resolution
Pinkett’s laboratory uses a combination of structural biology and biochemistry to determine the atomic structures of ABC transporter proteins and to relate these structures to function. The goal is to answer an unresolved question in biomedical research: how do the transmembrane domains of ABC transporters select and export a range of dissimilar substrates? Answering this will lead to an understanding of how organisms develop resistance to antibiotics and cytotoxic drugs. This would have broad implications for improving therapies for cancer and other serious diseases.
A Pew Scholar
Assistant Professor Heather Pinkett’s high profile success in determining the structure of a novel member of the ATP Binding Cassette (ABC) class of transporters was recognized in 2010 by the Pew Charitable Trusts. As a Pew Scholar, Pinkett garnered both recognition and research support to continue her work into the molecular basis by which ABC transporters transfer solutes across biological membranes. Pinkett’s research focuses on a fundamental biological mechanism with profound implications for human health. ABC transporters provide the means by which bacteria become resistant to antibiotics and cancer cells become resistant to chemotherapy.