Bryan Schmidt
Class of 2007
Biochemistry, Biophysics and Structural Biology
I was struck by how open and friendly people in the department were, and how the traditional barriers between students and faculty didn’t seem to exist. Plus, the students actually seemed happy here!
I had never been to California until I began recruitment at graduate programs. So when I visited Berkeley, I wasn’t sure what to expect. I was struck by how open and friendly people in the department were, and how the traditional barriers between students and faculty didn’t seem to exist. Plus, the students actually seemed happy here! These qualities really stood out to me as unique to Berkeley (whereas most programs I was looking at featured both depth and breadth of great research). I went to college at Indiana University, and I grew up in St. Louis, and so without hesitation I packed everything into my car and drove a couple thousand miles to my new home in California.
And I’ve never regretted it since. I am about to enter my fifth year at Berkeley (it’s also my final year – yes, we really do graduate on time here). I have loved living in Berkeley. The city itself is unique in its quirks - in a good way - and San Francisco is just a short subway ride away. Plus, I am a reasonable driving distance to Redwood forests, Tahoe’s ski slopes, multiple national parks, and Napa and Sonoma wine country. And I have found plenty of time to explore all these great opportunities.
But Berkeley isn’t merely a fun place to be a graduate student; we also do some amazing science here. In James Berger’s lab, my project uses a mix of X-ray crystallography and biochemical assays to understand the mechanism of type II topoisomerases. Each cell has about six feet of DNA crammed into the tiny confines of its nucleus, and topoisomerases manage the entanglements that inevitably arise during events such as DNA replication. To do this, topoisomerases must temporarily cleave DNA, which makes these molecular machines a cellular Achilles’ heel. These enzymes have been successfully exploited by small molecules that disrupt the DNA cleavage state and serve as widespread antibiotics and anticancer agents. We have long known that topos cleave DNA, but an understanding of the chemistry and control of cleavage has remained elusive. I used a chemically modified DNA as a suicide inhibitor to trap the ordinarily short-lived cleavage state, and subsequently purified enough of the complex to grow crystals and determine its structure which revealed its chemical mechanism. We learned that type II topos use a novel variation of a canonical mechanism in which only one of two metal ions plays a direct catalytic role. The structure also revealed how the enzyme avoids dissociation during cleavage, Overall, my work helped explain how the fidelity of DNA breakage and rejoining is maximized to protect the genome from the accidental formation of toxic DNA lesions during supercoiling management and chromosome disentanglement.
Undergraduate Degree: Indiana University
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