Wimley Lab
Membrane protein models and combinatorial chemistry — designing peptide assemblies that interact with lipid bilayer membranes for applications in drug design, delivery, and diagnostics.
Research Assistant
In Dr. William Wimley's lab (George A. Adrouny Professor of Biochemistry at Tulane School of Medicine), Evan used PDB membrane protein models with combinatorial chemistry to design peptide assemblies that interact with membrane proteins and lipid bilayers.
The work involved identifying membrane-spanning peptide pore structures using high-throughput screening — including the pHD peptide family (nanopores activated at pH < 6) and macrolittins (evolved from melittin, the primary cytolytic component of bee venom).
The lab's approach — synthetic molecular evolution — uses iterative rounds of peptide library design, synthesis, and functional screening to evolve peptides with specific membrane-interacting properties. This has produced peptides effective as antibacterial agents in whole blood, pH-responsive drug delivery vehicles, and self-assembling biosensor components.
Lab Context
- •$1.6M NIH grant for nanopore medicine research
- •Combinatorial peptide libraries with 10,000+ variants per screen
- •Collaboration with Tulane Biochemistry and Biomedical Engineering departments
- •Applications spanning infectious disease, oncology, and diagnostics
Molecular Visualization
Lipid bilayer membrane with self-assembling peptide pores. Six peptide subunits form a transmembrane channel allowing controlled molecular transport.
Evolved molecules.
Through synthetic molecular evolution, the Wimley Lab has developed peptide families with distinct membrane-interacting properties — each designed for a specific biomedical application.
Macrolittins
Evolved from melittin (bee venom)Form large, stable pores in lipid membranes at nanomolar concentrations. Potent antibacterial activity maintained in physiological conditions.
pHD Peptides
Synthetic molecular evolutionpH-dependent nanopores that remain inactive at physiological pH (7.4) and activate at acidic pH (< 6). Ideal for tumor-targeted delivery.
ATRAM
Acidity-Triggered Rational Membrane insertionPeptide that inserts into membranes only under acidic conditions, serving as a molecular switch for controlled membrane disruption.
From membrane to medicine.
Antibiotic-Resistant Drug Design
Peptide assemblies that bypass conventional resistance mechanisms by disrupting bacterial membranes through physical pore formation rather than metabolic inhibition. These peptides remain effective even in whole blood environments — a critical benchmark that most antimicrobial peptides fail.
pH-Responsive Drug Delivery
The pHD peptide family (pH-dependent) forms nanopores that activate specifically at pH < 6, enabling targeted drug release in acidic tumor microenvironments. This selectivity means the delivery vehicle is inert in healthy tissue and activates only at the disease site.
Biosensor Engineering
Self-assembling nanopore structures that can be engineered to detect specific molecular signatures. The controlled geometry of peptide pores enables single-molecule detection capabilities for diagnostic applications in infectious disease and cancer biomarkers.