Chemistry major Erin Berlew had been working in the lab of Lou Charkoudian ’03, which conducts wet-lab research focused on understanding how bacteria carry out some of their biosynthetic reactions, since the assistant professor returned to her alma mater in 2013. And broadly, the work done in that lab provided the jumping off point for Berlew’s senior thesis, “A bioinformatics-driven investigation into the structural diversity of type II polyketides.”
“Type II polyketides are a class of natural products produced by bacteria—specifically Streptomyces bacteria, the genus that give dirt its distinctive smell—which are of interest to researchers because of their properties as antibacterial, anticancer, antifungal, and antiviral agents,” explains Berlew. “Structurally, type II polyketides are quite difficult to synthesize in lab, so research has focused on ways to optimize and manipulate bacterial production of these molecules so they can be better used as therapeutic treatments.”
Interested in determining how type II polyketides have evolved to produce such structurally diverse molecules, Berlew and Charkoudian, in collaboration with Dr. Maureen Hillenmeyer at Stanford University, started compiling a catalog of all type II polyketides of known gene sequence and structure, analyzing the evolution of a pair of proteins in type II polyketide synthases thought to control the length of the molecule’s carbon backbone.
How did Lou help you develop your thesis, conduct your research, or interpret your results?
She has been an incredible resource and source of support for me over the past two years. Lou is very collaborative in her approach to research mentorship. When new results came in either from our end or from the West Coast team, we would discuss the new information together and decide on the next steps for the project. She taught me a great deal about drawing conclusions from large amounts of data as well as the importance of collaboration in research.
What did you learn from working on your thesis?
This project taught me a variety of new skills in using bioinformatics tools to draw conclusions about bacterial evolution. In my opinion, the biggest takeaway from this project is the type II polyketide catalog, which identified 78 polyketides of known producing sequence and structure and indexed key pieces of information about each of these molecules. Most importantly, this catalog will be open-source and maintained on the Stanford website so that other research groups can use it as a resource so that they have as complete information on the scope of type II systems as possible.
Slide culture photo: (cc) CDC/Dr. David Berd
“What They Learned” is a blog series exploring the thesis work of recent graduates.