Santos, Andrew

Doctor of Philosophy
Brett Finlay
Toronto, ON.
Exploring how pathogenic E. coli manipulate host intracellular signaling to cause disease
Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC; EHEC) are foodborne enteric pathogens that cause severe diarrheal disease worldwide. While EPEC is primarily an infection seen in the developing world, EHEC is among the top five foodborne illnesses requiring hospitalization in Canada, with over 22,000 infections in Canada each year and a healthcare burden approaching $240 million each year. My research aims to understand how EPEC and EHEC manipulate normal human cell functioning during infection in order to cause disease. These bacteria are able to manipulate the human cells by using a type III secretion system, which functions as a molecular needle, to inject bacterial proteins and enzymes into host cells. Once within the host cells, these bacterial proteins target a variety of human cell functions, including interfering in the cell’s ability to trigger an immune response or undergo programmed cell death. Importantly, bacterial proteins directly modify human proteins during infection, and looking at these modifications would reveal how bacterial proteins go about manipulating human cell functions during infection. Using proteomics techniques, I study how bacterial proteins modify human proteins and pathways in human intestinal cells during infection, in an effort to understand the mechanisms by which bacteria manipulate infected human cells.
My hope is that I'm able to further characterize how these pathogens cause disease. I'd like to gain a understanding of how EPEC and EHEC affect the infected human cells on a global level, that is to understand how they impact the cell signaling systems within the infected host. Up until very recently, research in this area looked only at how a single bacterial protein interacted with a single human protein or pathway, but my goal is to look at how bacterial infection impacts infected human cells on a system-wide scale.

I have always been a curious person. While completing my undergraduate degree, I found that the way that scientists made their discoveries was fascinating. These scientists saw a problem or lacked an understanding of some biological truth, and they needed to come up with some clever way to figure out the problem. Both the clever techniques and ultimately the answers those researchers found held value. I found the prospect of coming up with those clever ideas and finding those solutions exciting.