Research
The Chemical Biology of Microbes and Membrane Proteins Lab is driven by a fundamental interest in how proteins function at the molecular level. The team seeks to establish quantitative structure-function relationships and leverage these insights to identify and target novel regulatory sites for inhibitor design. The lab is at the interface of chemical biology, structural biology, biochemistry and cell biology.
Several of the lab's research directions include:
Antibiotic resistance mechanisms
Antibiotics have been foundational to modern medicine, dramatically reducing mortality from bacterial infections and saving millions of lives. However, their effectiveness is increasingly threatened by the emergence of antibiotic resistance, which is the ability of bacteria to evade or withstand these drugs.
Resistance arises through several mechanisms, including active drug efflux, mutations in target proteins, decreased membrane permeability and enzymatic degradation of antibiotics. The Traaseth lab focuses on one of the most widespread and clinically significant defense strategies: the active efflux of antibiotics from the cell.
This project aims to elucidate the molecular mechanisms underlying antibiotic transport and leverage these insights to design inhibitors that block efflux, thereby restoring the efficacy of existing antibiotics.
Cellular signaling mediated by receptor tyrosine kinases
Receptor tyrosine kinase genes in humans regulate essential biological processes, including embryogenesis, adult tissue homeostasis and metabolism. These receptors exhibit tightly controlled spatiotemporal expression and activation patterns during development and throughout adulthood.
Dysregulation of receptor signaling through mutation, overexpression or aberrant activation can drive a wide range of human diseases, including cancer and other growth disorders. The goal of this project is to elucidate the molecular mechanisms that govern receptor tyrosine kinase regulation in human health and disease. The team aims to understand how structural dynamics, receptor oligomerization, and interactions with ligands and downstream signaling partners control activation and signal propagation.
These studies will seek to provide a mechanistic framework for identifying new strategies to modulate receptor activity and develop targeted therapeutic interventions.
Protein mechanisms and method development
The lab is broadly interested in understanding how proteins carry out diverse and complex functions at the molecular level. To uncover how these molecular machines perform work, the lab integrates:
- Cryoelectron microscopy to determine structures and delineate conformational ensembles.
- Nuclear magnetic resonance spectroscopy to probe dynamics across timescales.
- Computational approaches to reveal additional atomic-level detail.
These data are combined with functional measurements to establish quantitative structure-activity relationships.
While established methods can address many biological questions, others require the development of new approaches. To meet these challenges, the lab also advances methodologies that improve the sensitivity, resolution and feasibility to apply cryoelectron microscopy and nuclear magnetic resonance spectroscopy.
These innovations enable more-accurate and efficient characterization of challenging biomolecular systems, particularly membrane proteins. Membrane proteins represent a major class of therapeutic targets.