Anna Brogan, a BMB undergraduate researcher, takes part in Poster Session Exhibition
Anna Brogan, a junior majoring in biochemistry and molecular biology within the Biochemistry and Molecular Biology (BMB) Department, has always shown an interest in science. During her high school experience in Glen Rock, New Jersey she began to develop a fascination with biology, chemistry and especially the chemistry related to biological systems. Brogan became a fan of Penn State and its atmosphere the moment she stepped foot on the University Park Campus and once she learned that Penn State had a department tailored exactly to what she hoped to study in the future she was hooked.
In the 2 years since she has been at University Park she has taken full advantage of the opportunities available to its students and gotten involved in working in a lab as an undergraduate researcher. She currently works in Keiler Lab working under the direction of Dr. Kenneth Keiler, a professor of biochemistry and molecular biology. Brogan recently submitted and presented at the Eberly College of Science Undergraduate Poster Exhibition. The title of her poster presentation was reflective of her individual research project in the lab, “Synthesis, Characterization and Target Identification of Quinoline Antimicrobials”.
Her project involves the characterization of a novel class of antimicrobials known as the quinolines. These antimicrobials were discovered in a screen of small molecules and inhibit a cellular pathway known as trans-translation. This pathway rescues ribosomes stalled in translation and is unique that it is only found in prokaryotic cells. Inhibitors to the pathway do not affect humans but kill bacteria, so the pathway is ideal for antibiotic development. After Brogan made the discovery she synthesized analogs of the parent compound and tested for their antimicrobial characteristics. Growth inhibition, toxicity and ability to inhibit spore germination of all compounds was characterized in Gram-positive and Gram-negative bacteria. She was then able to confirm their molecular target as the trans-translation pathway. Moving forward, she plans to use chemical biology techniques to identify and confirm molecular targets and mechanisms of action of the quinolines.
As most juniors, Brogan is looking to the future. She is not completely certain what her future career goals will be, but hopes to pursue either an M.D, Ph.D or an M.D/Ph.D program. No matter what program she gets involved in her desire is to someday take part in biomedical research and possible conduct research in infectious diseases.
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.
