Grant: Discovery Grants Program - Individual

Proteins act as components of life's molecular machinery. Many important biological processes are co-ordinated with extreme precision by proteins through their interactions with macromolecules like carbohydrates, or with small molecules including primary and secondary metabolites. My research group is pursuing several axes of research to apply control over protein function towards developing new tools for biotechnology. Firstly, we will develop and apply new strategies to engineer biosensors, which are detection systems consisting of biological components that produce a measurable response to a target molecule. By tailoring specific protein components that switch genes on or off within engineered microbial cells, we will reconfigure them to detect specific molecules, providing us with useful tools to optimize the bioproduction of valuable chemical building blocks. We will also engineer antibody-like proteins to bind to distinctive cell surface carbohydrate molecules-known as glycans-which are made up of a structured pattern of sugar building blocks. Because these glycans act as biomarkers to various states of health and disease, biosensors engineered to detect them can be useful as accurate diagnostics (e.g., to cancer). Secondly, we will establish new tools and methods to control the enzymes that assemble complex molecules using sugar building blocks. We will accomplish this in one case by engineering the enzymes that add sugar units to assemble therapeutic molecules. Altering the sugar unit that the enzyme attaches will allow us to produce new therapeutics. In another case, we will target the human enzymes that assemble glycan structures on cell surfaces in order to identify molecules that block their activity, which will be useful towards therapeutics to treat diseases like cancer where these enzymes are abnormally overactive. Thirdly, we will use new methods that we have devised to engineer enzymes that are useful tools for "green chemistry" towards producing flavour molecules, medicines, and polymers. These particular enzymes catalyze the transfer of electrons in key biotransformation steps. We will identify promising enzymes from nature and then engineer improved mutants by directed evolution.