Welcome to the Martens Group @ ULB
We are a structural biology group lead by principal investigator Dr Chloé Martens and based at the Université Libre de Bruxelles (ULB) in Belgium. Our research focuses on membrane transport mechanisms.
We are interested in understanding how resistant bacteria expel antibiotics, how drugs are transported within the human body and how hormones are distributed in plants.
Research Themes
Drug Transporters
Transport proteins embedded in the biological membrane act as gatekeepers and select molecules that can cross this hydrophobic barrier.
Most of these transporters are highly specific for their substrates but a significant subset is polyspecific. In humans, polyspecific transport proteins modulate drug uptake profiles in the body and alter their efficacy.
Antibiotic Resistance
Antibiotic resistance in bacteria is facilitated by the expression of efflux pumps able to expel various cytotoxic agents, thereby diminishing their intracellular concentration and giving bacteria a selective advantage to develop other resistance mechanisms. Allosteric modulation of efflux pumps dynamics is a promising approach to counteract their action.
Hydrogen-Deuterium eXchange Mass Spectrometry (HDX-MS)
for transporters
The conformational dynamics of transporters are the linchpin of their function. Transport proteins alternate between different conformational states open to opposite sides of the biological membrane to allow substrate transport. HDX-MS is well adapted to follow shifts between theses different conformational states. This method is currently not easily applicable to the study of transporters in native-like environments. We are developing workflows and methods to facilitate the study of transporters in complex and heterogeneous environments closer to the cellular one.
Solute Carriers involved in drug transport
The human L-type amino acid transporter LAT1, in complex with its chaperone CD98hc, is highly expressed at the blood–brain barrier, where it mediates the uptake of essential neutral amino acids into the brain. This privileged localization also makes LAT1 a major route for drug delivery to the central nervous system, as it recognizes several clinically relevant drugs and prodrugs, including L-DOPA, gabapentin and melphalan. We study the functional dynamics of LAT1-CD98hc using different biophysical and biochemical approaches, in particular hydrogen/deuterium exchange mass spectrometry.
Multidrug Efflux Pumps from Gram-Positive Bacteria
Bacteria have developed an efficient strategy to avoid being killed by cytotoxic drugs. They express membrane proteins known as multidrug efflux pumps that actively expel molecules of various size and shapes, including antibiotics, out of the cytoplasm. The molecular basis underlying substrate specificity is not understood, preventing rational approaches for inhibition.
