CHEMICAL BIOLOGY, BIOORGANIC CHEMISTRY AND PROTEIN ENGINEERING

The research in our group centers around the concept of chemical biology. That is the introduction of small molecules into biological systems for the purpose of tracking or perturbing cellular processes. More particularly we are interested in introducing small unnatural moieties into the biopolymers of life. Methodologies that we rely upon include organic synthesis, biochemistry and molecular biology.

Metabolic Engineering

Metabolic engineering is the introduction of unnatural functionality into biosynthetic processes. This results in the production of proteins, oligosaccharides and DNA with inherent unnatural functionality that can be used for tracking, dynamics studies, and subsequent chemical modification. One of our focuses within metabolic engineering is to use this technique to remodel the surfaces of eukaryotic viruses, which has been limited by solely genetic approaches. Many of the basic science and therapeutic applications, such as gene therapy, oncolytic viruses, and live vaccines, have been hindered by the inability to sufficiently control surface interactions.

Protein engineering
Protein pharmaceuticals represent a rapidly expanding section of the pharmaceutical industry, this has been exacerbated by recent specificity issues with more traditional drugs. However, protein-based drugs are faced with their own set of limitations, particularly introduction, lifetime and immunogenicity. We focus on diminishing interactions with proteases and the complement system by introduction of unnatural functionality into the protein backbone.

Bioorthogonal reaction development
Precise chemical modification within a physiological context is a key hurdle facing many biosciences. The overwhelming diversity of native functionality complicates specific modification. Additionally, the environment dictates 55 M water, neutral pH and 37°C.
Realistically the target molecule will be in low abundance and the labeling molecule should also be to prevent background. Our lab is focusing on the development of fast, chemoselective reactions that create stable linkages under these conditions. Of particular interest to us are electrocyclic reactions aided by molecular recognition events.