Synthetic Biology

Biography

Biography: Richard McLean

Abstract

Campylobacter jejuni is the leading cause of human gastroenteritis in the developed world with cases in of Campylobacteriosis in Canada numbering nearly 50% of all bacterial foodborne illness. Primary infections are typically self-limiting however numerous secondary sequelae can develop including reactive arthritis, irritable bowel disorder, inflammatory bowel disease, and Guillain-Barre syndrome, the leading cause of acute fl accid paralysis in North America. Because as much as 70% of human Campylobacteriosis can be traced to the consumption of contaminated poultry, this project aims to prevent C. jejuni from proliferating in the chicken gut. Numerous approaches have been attempted previously including the addition of bacteriophages or bacteriocins to the feed, chicken vaccination, positive selection of C. jejuni free birds and a variety of methods to limit physical exposure of the birds to the bacterium. This project uses a synthetic biology approach to engineer the human gut commensal Bacteroides thetaiotaomicron to produce and secrete Nano-bodies within the chicken gut. Nano-bodies were raised against C. jejuni flagella and the focus of this project was to establish adequate expression levels, integrate required genes into the genome of B. theta and demonstrate the secretion of functional protein. The benefit of this approach will be the continued production of Campylobacter-active compounds within the chicken gut, which would be an economic and technological advancement over feed supplementation. In addition, this approach will enable the rational selection of therapeutic targets to help avoid the development of resistance.