2006 Eighth Annual Beckman Scholars Symposium
Beckman Scholar Alumni Speaker

Tracy LaGrassa , Ph.D.
1999 Beckman Scholar Alumni
B.S. - State University of New York, Stony Brook
Ph.D. - University of Heidelberg
Presently in Post-Doctoral Position at Columbia University

Organelle size control: A phospho-switch tells yeast vacuoles to stay small

.Eukaryotic cells contain an elaborate and dynamic endomembrane system, a network that serves to both compartmentalize and integrate cellular activities. Although much of the machinery responsible for organelle biogenesis has been identified, we are only beginning to understand the mechanisms that regulate their size and shape. Toward this end, we have focused on the yeast vacuole, which is easily visualized by light microscopy and amenable to biochemical and genetic analysis. Its morphology is exquisitely tuned to changes in the environment: When cells are placed into hypertonic medium, the vacuole is a first line of defense, rapidly undergoing fragmentation to restore the cell’s osmotic balance. We used this phenomenon as the basis for a genetic screen to identify regulators of vacuole membrane flux. We found that maintenance of the fragmented phenotype requires the vacuolar casein kinase I Yck3: when Yck3 is absent, salt-stressed vacuoles undergo fission, but become large again. Further experiments confirmed that Yck3 is a negative regulator of vacuole membrane fusion; specifically, it interferes with vacuole-to-vacuole tethering. Because Yck3 also promotes efficient vacuole inheritance, we propose that tethering complex phosphorylation is part of a general, switch-like mechanism for driving changes in organelle architecture.

My first undergraduate life was as a writer (poems mostly) at Bard College. After graduating, I became fascinated with viruses – such beautiful examples of form, so compactly efficient in their deadliness – and so returned to school with dreams of becoming a strapping virus hunter. I started a second bachelor’s degree, now in biochemistry, at SUNY Stony Brook, and began doing virology research (on HIV) under the incredible mentorship of Professor Carol Carter. I thoroughly fell in love with science as a result of my experience in her lab; with the privilege of two full-time summers in the Beckman Scholars Program (1999-2000), I felt first-hand the excitement and challenge of a life in research. I then had an opportunity to engage with the world both microscopic and huge: I moved to Germany to enter the inaugural class of the International Graduate Programme in Molecular and Cellular Biology and Biochemistry at the University of Heidelberg. Last year, I completed my NSFGRFP-funded PhD (my “Dr. rer. nat.”) with an enthusiastic young advisor, Dr. Christian Ungermann, at the University’s Biochemistry Center, using yeast as a model organism to understand mechanisms of intracellular membrane traffic. I am now back in New York, and recently began an NIH-funded postdoctoral fellowship with Professor Stephen Goff at Columbia. My research focus: membrane trafficking during assembly of my beloved viruses.