Posted Aug 13, 2013

A group of Lewis-Sigler Institute researchers have joined with university undergraduates to publish A New System for Comparative Functional Genomics of Saccharomyces Yeasts in the journal Genetics.

With genome sequencing in humans and other organisms quickly becoming easier and cheaper, the next big challenge for biology is to translate genome sequences into gene functions. The researchers tackled this problem in a novel way by harnessing the power of undergraduate researchers. The group experimentally tested gene functions in the sequenced but otherwise poorly studied yeast Saccharomyces bayanus var uvarum. This yeast, perhaps best known as a yeast that gives champagne its fizz, is evolutionarily related to the well-studied baking and brewing yeast Saccharomyces cerevisiae. The team of students leveraged work in the well-studied yeast to select and carry out hundreds of microarray expression analysis experiments characterizing the response of S. bayanus to a range of environmental conditions and stresses. The students also isolated mutant strains to identify genes necessary for nutrient metabolism and for resistance to copper.

The team of 51 Princeton undergraduates, most of them members of the QCB program enrolled in the QCB301 Project Laboratory, were joined by Princeton graduate students and technical staff and by visiting students and faculty from Spelman College. The project was led by former Lewis-Sigler Fellows Dr. Amy Caudy (now an assistant professor at the University of Toronto) and Dr. Maitreya Dunham (now an assistant professor at the University of Washington), and joined by faculty Dr. Coleen Murphy, Dr. Manuel Llinas, Dr. David Botstein, and Dr. Olga Troyanskaya.

The expression data were analyzed by a Princeton graduate student, Yuanfang Guan (now an assistant professor at the University of Michigan) and her supervisor Dr. Olga Troyanskaya to predict the functions of genes in this understudied organism. The data reveals significant differences in how S. bayanus processes sugars, and uncovered an entirely novel set of genes that respond to oxidative stress. One of the anonymous reviewers of the paper wrote, "This research required a heroic experimental and computational undertaking.  It will strongly influence comparative and evolutionary genomicists as they design similar strategies to functionally annotate other poorly studied organisms that have well-studied relatives."

Many of the student authors of this study have moved on to graduate work in biology, building on the research experience gained at Princeton. Author Maitreya Dunham commented, "Our work is a great demonstration of the substantive contributions undergraduate researchers can make to scientific discovery."  She also speculated that the experimental, computational, and educational approaches could be used to characterize many other sequenced but understudied organisms while simultaneously building meaningful research experiences for students.

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