While many people (not Dr. G) fear snakes or spiders, I have been afraid of antibiotic resistant bacteria since I read a book about it in middle school. But unlike my other fears, I don’t want to avoid antibiotic resistant bacteria. I want to do something about it. That’s one of the reasons why the Brennan lab stood out as a good match for me this summer.
My project in the Brennan lab is primarily focused on a bacterial toxin called HipA (high persistence A), a protein that mediates multidrug tolerance through a mechanism known as persistence. Essentially, during times of stress, such as the presence of antibiotics in an environment, HipA causes bacterial cells to enter a dormant state in which all cellular activity stops. During this time, antibiotics are not effective against them because the functions targeted by antibiotics are shut down. After a period of time, the levels of HipA in the cell decrease, and the cell returns to normal functioning. These cells are known as persisters because they survive antibiotic treatment. You can learn more about bacterial persistence here. The Brennan lab is collaborating with a drug discovery company to find molecules that bind with HipA, potentially reducing its ability to induce dormancy. In the future, these findings could lead to improvement of antibiotics.
My project involves isolating HipA from E. coli that are engineered to overexpress it, or make much more of it than they usually would. HipA is a kinase, which means that it transfers phosphate from ATP to other molecules, and its activity can be measured by its ability to autophosphorylate, in which it uses its kinase abilities to phosphorylate itself. I can treat HipA with the drug precursors to determine if any of them can inhibit HipA’s autophosphorylation, since if HipA cannot phosphorylate itself, this is an indication that it has lost its function as a kinase. My longterm goal is to determine which, if any, of the drug precursors inhibit HipA’s function. You can read more about HipA and phosphorylation here.
Field trip to the lemur center!
