Our Research
Explore our groundbreaking work in chemistry and biology.
Biocompatible Chemistry
Interfacing Chemical Catalysis With Engineered Microbes for Expanding Biomass-Sourced Materials
Metabolic engineering—a process in which an organism is genetically engineered to produce valuable commodity chemicals from sugar—is a powerful strategy to source industrial chemicals and drugs from biomass. However, several persistent problems limit this approach. Product accumulation can trigger microbe death, which limits titer yields.
Moreover, a relatively limited number of discrete chemical products can be produced by metabolic pathways alone, especially in comparison to the massive variety of products that can be produced with synthetic chemistry.
Catalysis & Biology
To address these problems, we are interfacing catalytic upgrading reactions with microbial production of chemical building blocks in single-flask processes. Using approaches fundamentally rooted in green chemistry, we are identifying chemical reactions that can upgrade bacterial metabolites concomitantly with bacterial metabolite production.
This will greatly expand the types of products that can be sourced from biomass while minimizing toxicity and increasing flux through the system.
Dynamic Biomaterials Cell-Activated Soft Materials
To close the gap between the environments in which cells are grown for research purposes and the cytoarchitecture they experience in native tissue, we are working toward dynamic hydrogels that can serve as three-dimensional cell culture matrices and soft materials that can act as cell-activated wound-healing materials.
Two-dimensional cell culture—for example, the growth of adherent cells on a glass coverslip—is an indispensable technique in molecular and cell biology. However, the conditions in which these cells are grown (e.g., in aqueous culture media) differ drastically from the cytoarchitecture cells experience in native tissue.
The differences in the chemical, physical, and mechanical characteristics of these environments can make it difficult to translate results from cell culture to in vivo systems.
Responsive Biomaterials
To clear the path from experimental results to practical applications, we are working toward dynamic hydrogels that can serve as three-dimensional cell culture matrices and soft materials that can act as cell-activated wound-healing materials. To this end, we are developing dynamic covalent soft materials that alter their mechanical properties in the presence of cellular events, such as ion efflux and oxidative stress.
Using principles from synthetic organic/inorganic and physical organic chemistry, we are rationally designing chemistry that undergoes chemoselective transformations to alter the dynamics of the crosslinking components and, by extension, the bulk properties of the material.
Molecular Imaging
Self-Immolative Probes for Spatial Mapping of Cellular Reactive Oxygen Species
Cellular reactive oxygen species (ROS) are important metabolites derived from dioxygen (O₂) that are a double-edged sword for living organisms: though uncontrolled ROS production and distribution can lead to oxidative damage of nucleic acids, lipids, and proteins, causing disease states, emerging evidence points toward ROS’ role as critical signaling molecules that mediate protein phosphorylation and transcription factor activity.
Progress in the past decade has yielded small molecule fluorophores capable of monitoring ROS production in living cells, providing biologists with a powerful toolkit to visualize ROS production in real time. However, these small molecules are free to diffuse through the cell, greatly limiting the spatial information they can provide about the genesis of cellular ROS.
Targeting Cellular ROS
Drawing on established chemistry in the field of bioconjugation, as well as new chemistry established in the Domaille lab, we are developing new chemical triggers that covalently tag proteins directly involved in ROS generation. This will enable us to better understand the spatial distribution of cellular ROS so that we can identify key players in ROS signaling pathways.
