November 16, 2018 - Tis the season for infection and sickness! In most cases people don’t give the “why” they are sick a second thought and simply focus on the fact that they are sick. For undergraduate student Emily Snell this has never been the case. She has always had a curiosity about human infection and the pathways pathogens take inside of the body and has always wanted to pursue a degree and career that would satisfy those interests. It’s because of this, its relevance to healthcare and emphasis on the understanding of disease that she chose to study microbiology. It was the dedication to the life sciences and the research being conducted in the Biochemistry and Molecular Biology Department though that made her make the trip from her home town of Pittsburgh Pennsylvania and chose Penn State. “Being among the top 50 research universities, I knew that I could pursue my interests in biochemistry while being among world-class faculty,” said Snell.
As a student at Penn State, Snell has made many decisions and has taken advantage of many opportunities that have helped her get to where she is today. In the fall semester of 2016 she made the decision to become an Undergraduate Researcher and joined the Keiler Laboratory. There she works under the direction of Dr. Kenneth Keiler, a professor of biochemistry and molecular biology, and profiles the In vitro and Ex vivo activity of Tetrazole-based trans-Translation inhibitors in Bacillus anthracis. In a poster she presented at the Eberly College of Science Undergraduate Poster Exhibition she detailed her work and research.
Snell’s research revolves around the antibiotic resistant bacteria that top the list of causes of death around the globe. Over time, drug-resistant bacteria have evolved to carry genes that make current antibiotics useless, therefore causing fatal infections. One such bacteria, Bacillus anthracis, is the causative agent of anthrax and has been classified as a bioterror agent because of its pathogenicity and ability to thrive for decades as spores. The Keiler laboratory works with a ribosome rescue pathway known as trans-translation which is essential in bacterial cells. The lab has been able to identify compounds that inhibit this pathway, using a high-throughput screen, and has determined them to have antibiotic activity.
Snell works with a specific class of trans-translation inhibitors named Tetrazoles and her research thus far has proven them to be extremely active in a broad-spectrum of bacteria. These Tetrazoles are able to inhibit the germination of spores, protect macrophages from death following infection, and their low cytotoxicity levels make them good candidates for antibiotics of spore-related infections.
Snell is currently a senior graduating in May of 2019 and hopes to attend medical school in the future to pursue a career as a physician. As an undergraduate student, her summers have been spent working for many physicians who have conducted their own research and ideally, she hopes to one day conduct her own research while also practicing medicine.
The Keiler Lab:
The Keiler Lab’s mission is to understand how protein quality control is maintained during stress responses and homeostasis by trans-translation and alternative pathways. The lab’s goal is to characterize the fundamental biochemistry, genetics, and cell biology of these systems, and to use this knowledge to develop antibiotics and tools for basic research.
Recently, the lab’s identification of small-molecule inhibitors of trans-translation has opened new opportunities for translational research and basic science. They have identified and characterized inhibitors of trans-translation, and showed they have broad-spectrum antibiotic activity. There are currently several projects to advance drug development with these compounds.
The inhibitors they have identified have also provided new tools to understand the role of trans-translation in bacterial physiology and genetics. Individuals within the lab are using these inhibitors to examine the physiological response of bacteria to losing trans-translation activity, and for chemical genetic experiments to understand why trans-translation is universally conserved in bacteria.
The Keiler Lab’s experience with inhibitors of trans-translation led them to explore other pathways that are candidate targets for antibiotic development and chemical biology studies. In collaboration with Sarah Ades (Penn State), they have engineered and validated assays for inhibition of two mechanisms that are important for maintenance of the cell envelope in Gram-negative bacteria: σE-directed transcription, and Hfq-sRNA repression of gene expression.