Grant: CIHR Fellowship

Antibiotic resistance remains one of the most pressing crises facing modern medicine. We use antibiotics as weapons against bacteria, while bacteria find ways of deflecting our attack. Existing forms of resistance make current antibiotics nonfunctional, and newly emerging resistance makes even our best new antibiotics stop working. Currently, our only option when we encounter resistance is to switch to a different antibiotic, and we're rapidly running out of good ones to use. This is because resistance is widespread and frequently develops spontaneously. We need to understand resistance better to "hit back" when we encounter it. By counteracting resistance we can protect the usefulness of antibiotics and continue to treat the patients that suffer from antibiotic-resistant infections. The tools of synthetic biology can help, using libraries of de novo proteins - proteins that have never before existed in nature. I will develop a method to predict the emergence of new antibiotic resistance activities by screening vast libraries of proteins for new antibiotic resistance activities. Proteins that produce resistance will indicate mechanisms of resistance that could also emerge in clinical bacteria. These proteins will teach us about the way a bacterium escapes antibiotics, so we can learn to counter that resistance even before we introduce that antibiotic into patients. Once I have identified proteins that produce resistance, I will determine the chemical mechanism the proteins use to make the bacteria resistant. This information will help us better understand the likely causes of resistance when we use an antibiotic in the clinic. Thus, using this broad screening method for antibiotic resistance, we will be able to better predict and anticipate where resistance will come from. We can even apply this strategy for the newest antibiotics as they are discovered. For the first time, we will be prepared when we find resistance and be able to immediately fight back