Tufts University School of Medicine Mecsas Lab, Boston, MA
My internship at Tufts Medical School has allowed me to experience scientific research on a day-to-day basis. I spent the summer working in the Mecsas Lab under the direction of Joan Mecsas. Dr. Mecsas employs six graduate students and one post-doc who work on a combination of microbiology and immunology projects. I worked closely with post-doc Anne McCabe on the bacteria Klebsiella, a Multi Drug Resistant (MDR) bacteria that has become a large problem in hospitals as we are currently unable to effectively fight this infections with safe drugs. Medical professionals have to use “last resort” antibiotics, which are toxic and can cause liver damage, to treat these infections. In previous years, the Mecsas Lab determined that genes involved in central carbon metabolism likely contribute to the cause of Klebsiella’s antibiotic resistance. This summer I worked on two projects, one in microbiology and the other in immunology, to help the lab work out the genetic details of this metabolic pathway.
My primary project involved completing a series of ROS assays (Reactive Oxygen Species) which have been shown to destabilize bacteria cells leading to their death. Certain genes involved in central carbon metabolism in Klebsiella lead to ROS resistance and thus were the focus of our assays. I grew Klebsiella knockout strains, focusing on gntr and gnd, in rich L media as well as in glucose and gluconate, both minimal media. I then back-diluted each sampled into one of the three media and then exposed each strain to hydrogen peroxide, a reactive oxygen species and plated each condition in technical triplicate and normalized it to the untreated control that was not exposed to Hydrogen peroxide. After many weeks of testing every combination of growth conditions repeatedly, we found that when grown in an L overnight, and back-diluted into glucose or gluconate, gntr survived notably less than WT and gnd survived notably better than WT. When grown and back diluted in minimal media, we found that both WT and gntr die at a higher rate than gnd. This data suggests that the type of sugar source in the initial media and in the back diluted media impacts ROS resistance. It also shows that gnd leads to high ROS resistance and gntr leads to low ROS resistance. We also found that when grown in an L overnight and back diluted into glucose or gluconate, both gntr and WT grew better in gluconate.
My second project involved using a mouse model to look at the interactions between Klebsiella and neutrophils, first line defense immune cells that fight bacterial infections. We used a sample of 15 mice and depleted half them of their neutrophils. We then infected all of the mice with the yaaA and ycgE knockout strains of Klebsiella and found that the mice that had been depleted had a significantly higher bacterial load than the control mice which had not been depleted. This confirms that neutrophils play an important role in immune system defense against pathogens like Klebsiella. We also found that the knockout strain ycgE recovered more of its bacterial load in the depleted mice than WT and yaaA indicating that it may play an important role in interacting with neutrophils. However, we need to do more experiments including qPCR to find out what exactly that role is.
I really enjoyed my experience at Tufts. The people I worked with were wonderful and I learned so much. It was so interesting to see how scientific research works in the real world and how different it is from what I have experienced in lab at Williams. I was often thrown into projects that I did not initially understand the science behind but was able to learn so much through the process of doing the experiments myself and through the mentorship of Anne and everyone else in the lab. Working in the Mecsas Lab this summer has also shown me how scientific collaboration is executed in a professional environment as everyone in the lab worked so well with each other. People were willing to pause what they were doing to help each other figure out what was going wrong in their experiments. Also, everyone was so kind and welcoming which made me feel comfortable asking questions which definitely enhanced my learning and overall experience this summer.
Before this internship, I knew I wanted to study biology. However, this summer has made me realize that I really like the small cellular level of biology as opposed the larger picture population level area. I have taken classes that focus in both of these areas and now know that I want to take more classes that focus on cellular level processes. I have also realized I like microbiology more than I thought I would and may wish to take the microbiology class at Williams. Prior to this internship I was also thinking that I wanted to go to medical school. I still think that this is what I want to do but given how much I have enjoyed this internship, I would now consider potentially doing a MD/Ph.D. in microbiology or immunology. I would also now consider specializing in an area in medicine with a research component as opposed to just being a practicing physician. I have learned this summer that I really enjoy lab work and would like to maybe work that into my future career choices.
I would like to thank the ’68 Center for Career Exploration, the Kraft Family, and especially everyone in the Mecsas Lab for providing me with the wonderful opportunity to do research this summer.
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