Research group Anna Seelig-Löffler

Functioning of the ATP-binding cassette (ABC) transporters

ABC transporters protect cells from intrinsic and extrinsic toxins and can cause drug resistance. Better understanding of their mechanisms of action and transport function could contribute to the development of new medications.

ATP hydrolysis in living cells measured by microphysiometry.

ATP-binding cassette (ABC) transporters belong to a family of membrane proteins that protect cells from lipid-soluble compounds. The ABC transporter most closely studied is P-glycoprotein (ABCB1). It has a major role in protecting the cell from intrinsic and extrinsic toxins. Overexpression of ABC transporters - either naturally or in the disease state - may lead to drug resistance, i.e. a person responds poorly, or not at all, to particular medications. Similar transporters are found in bacteria, where they are often the cause of antibiotic resistance. Mutations in the ABC transporters themselves may result in disease, such as gout and cystic fibrosis.

Substrate recognition, substrate specificity and transport mechanisms

We want to improve our understanding of the substrate recognition, substrate specificity, and transport mechanisms of ABC transporters. We have found a universally valid substrate recognition pattern for ABCB1; the more of these recognition patterns present in a transport substrate, the better it binds to the transporter. Knowledge of recognition patterns in substrates and their affinity to the transporter allows us to predict whether a substance will reach its site of action or not.

Novel biophysical methods shed new light on the problem

The use of novel biophysical methods such as titration calorimetry and microphysiometry allows us to follow substrate transport in the individual cell for the first time. A newly developed computer program also allows us to predict the substrate properties for the different transporters.

Medical applications

Elucidation of the recognition patterns and reaction mechanisms of various ABC transporters is leading to the better understanding of how drug resistance develops. Our work may serve as a foundation for the improved treatment of gout and cystic fibrosis.