Program: Scholar

There is currently a poor understanding of how a relatively harmless microbe can evolve into one that causes disease. However, analyzing microbial DNA indicates that these bacteria may exchange their DNA with one another, essentially sharing genes that cause disease. Some microbes have evolved into disease-producing organisms relatively recently, making them good models for examining how bacteria results in disease. That’s because we are more likely to relate genetic changes in bacteria to those that cause virulent disease when the changes are more recent. My team is conducting laboratory and computer research to analyze the role gene exchange plays in the development of disease-causing microbes, and to characterize the evolution of recent disease-causing microbes. Understanding how benign bacteria evolved into virulent disease-causing bacteria will increase knowledge of how bacteria cause disease and lead to genuinely new therapeutics and prophylactics to combat current disease-causing microbes, and hopefully help prevent new ones from emerging in the future.

I am studying protein folding, a poorly understood but fundamental cellular process by which proteins made in cells fold to attain their correct three-dimensional structures (shapes) and become active. When proteins in a cell do not become active, the result is abnormal function, which often leads to disease. Amino acids are the basic component of proteins, with hundreds of amino acids in each protein. The sequence of amino acids in proteins dictates how a protein folds into its proper shape and achieves its specific function. In some instances, proteins called molecular chaperones have been shown to help newly-made proteins fold properly. My research focuses on understanding how molecular chaperones function at the biochemical and cellular levels, and determining what goes wrong when certain proteins don’t fold properly. For example, one protein called von Hippel-Lindau relies on a particular molecular chaperone to fold correctly. The protein’s loss of function is often caused by protein misfolding, and leads to the major cause of renal cancer. Other diseases, such as Huntington’s and Alzheimer’s, are also associated with the improper folding of proteins. My basic biomedical work on molecular chaperones helps us understand a fundamental process (protein folding) required for good health. Ultimately, such studies may also provide valuable clues regarding how to tackle some diseases that arise from protein misfolding.

Naturally occurring cellular components such as enzymes are often the only tools available to perform biological research, a limitation that slows the pace of research and hinders the search for cures to human disease. The situation is similar to having your car break down in the middle of the street and having to make repairs using parts scavenged from neighbouring automobiles. A proper toolbox would greatly decrease the time required to perform the repair. My research examines the potential functions of ribonucleic acid (RNA), a cellular component which is vital for the development and functioning of all living things. I am examining the ability of RNA to replicate itself, without the help of protein, because RNA may be capable of important metabolic functions that are currently performed by protein enzymes. I am developing in vitro (in the test tube) techniques to isolate new RNA catalytic molecules. Because these artificially manufactured catalysts perform specific functions, they can be used as tools for conducting medical research. Ultimately, I will examine whether artificial RNA sequences can interact with existing cellular components. Such experiments give us a better understanding of natural processes within cells, perhaps leading to potent new genetic therapies for the treatment of disease.

DNA and RNA (the genetic matter in the cells of all living organisms) have properties beyond their function as storehouses of genetic information. I am examining ways we can exploit these other properties to develop new biomedical applications to combat disease. For example, DNA has a slight tendency to conduct electricity. I am investigating how to harness this conductivity to generate sensors that can detect and monitor hormones, metabolites (substances essential to metabolism), toxins, enzymes, drugs, proteins and other molecules in the blood or other body fluids. DNA has potential as an electrical tool to manipulate products at the molecular level. A major interest of mine is based on the discovery that synthetic enzymes made out of DNA and RNA can sometimes function as efficiently as naturally occurring enzymes. Enzymes act as catalysts to accelerate chemical reactions and cellular processes in the body, such as breaking down food during the digestive process. With huge, synthetic DNA and RNA libraries available, we have endless opportunities to create enzymes that perform specific therapeutic functions. Ultimately, we hope to synthesize nucleic acid enzymes to help counteract cancers and viral infections.