Membrane Transporters:
Decoding the Rules of Molecular Transport
Membrane transporters are the molecular gatekeepers of the cell, controlling the movement of nutrients, metabolites, toxins, and drugs across biological membranes. Many bacterial pathogens rely on multidrug efflux pumps to survive antibiotic treatment by actively exporting toxic compounds using cellular energy gradients. These proteins face a remarkable challenge: they must recognize and transport a wide variety of chemically unrelated molecules while preserving the integrity of the cell’s own metabolites. This requires transporters to balance competing demands—specificity versus promiscuity, transport efficiency versus flexibility, and robustness versus evolvability.
Our laboratory studies membrane transporters to uncover the sequence-level rules that govern these trade-offs. Using deep mutational scanning and barcoded pooled selections, we systematically perturb transporter sequences and measure how individual mutations affect substrate specificity, transport efficiency, and cellular fitness. These experiments generate comprehensive sequence–function maps that reveal how transport activity emerges from distributed networks of residues rather than single binding-site determinants. By comparing transporters across multiple protein families—including major facilitator superfamily (MFS), resistance–nodulation–division (RND), and small multidrug resistance (SMR) transporters—we seek to uncover general principles that govern how molecular transport systems recognize substrates, couple to energy sources, and evolve under environmental pressure.
Engineering Transport Systems for Biotechnology and Energy
Beyond their role in antibiotic resistance, transporters are essential components of engineered biological systems. In industrial biotechnology, the ability of cells to produce fuels, chemicals, or pharmaceuticals is often limited by the transport of molecules across membranes. Inefficient export of products can lead to toxicity, metabolic bottlenecks, and reduced yields.
Our research aims to transform membrane transporters into programmable components for synthetic biology. By combining large-scale experimental datasets with predictive models, we seek to design transporters with tailored substrate specificity, improved energy coupling, and optimized transport efficiency. These engineered transport systems could enable microbial factories to export biofuels, specialty chemicals, and metabolic intermediates more efficiently, unlocking new possibilities for sustainable biomanufacturing and bioenergy production.
