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 particularly interested in understanding how resistant bacteria expel antibiotics and how drugs are transported within the human body.
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 organic cation transporters OCT1, OCT2 and MATE1, MATE2 are expressed in hepatic and renal cells and play a key role in drug pharmacokinetics. The efficacy of common drugs is directly related to the function (and malfunction) of these proteins, which is to be expected since 40% of prescribed drugs are organic cations. We study the functional dynamics of OCTs using structural mass spectrometry (H/D exchange).
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.
