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Goodman, Brian Kruzick

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Brian Kruzick

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Goodman, Brian Kruzick

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2014 - 20162

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    Investigating Cytoskeletal Motor Mechanisms using DNA Nanotechnology
    (2014-02-25) Goodman, Brian Kruzick; Reck-Peterson, Samara Louise; Yin, Peng; Wong, Wesley; Gennerich, Arne; Mitchison, Timothy
    The microtubule cytoskeleton plays a vital role in the spatial-temporal organization of subcellular cargo required to maintain homeostasis and direct cell division. Cytoplasmic dynein and kinesin are opposite-polarity, microtubule-based motors that transport a wide variety of cargo throughout eukaryotic cells. While much is known about the stepping mechanism of kinesin from decades of study, cytoplasmic dynein's size and complexity has limited our understanding of its underlying motor mechanism. Here, a minimal, artificially-dimerized dynein motor was observed with two-color, near-simultaneous, high-precision, single-molecule imaging, which reveals the stepping pattern of each motor domain as dynein moves along the microtubule. Although the stepping behavior appeared highly irregular and erratic, with large variability in step sizes, side stepping behavior, and back stepping behavior, dynein did show evidence of tension-based, coordinated stepping. Furthermore, advances in DNA nanotechnology enabled us to engineer a synthetic motor-cargo system, referred to as a chassis, to investigate how multiple cytoskeletal motors work in teams to produce the myriad of motile behaviors observed in vivo. Specifically, the mechanisms that coordinate motor ensemble behavior was examined using three-dimensional DNA origami to which varying numbers of DNA oligonucleotide-linked motors could be attached, allowing control of motor type, number, spacing, and orientation in vitro. Ensembles of 1-7 identical-polarity motors displayed minimal interference with respect to directional velocity, while ensembles of opposite-polarity motors engaged in a tug-of-war resolvable by disengaging one motor species. This experimental system allowed us to test directly the tug-of-war proposed to occur during dynein's delivery to the microtubule plus-end by the kinesin Kip2. This work led to the mechanistic understanding that Lis1/Pac1, CLIP170/Bik1, and EB1/Bim1 proteins function to enhance kinesin's processivity, allowing it to win a tug-of-war and transport dynein toward the microtubule plus-end. Overall, this work elucidated mechanisms of ensemble motor function and dynein's stepping mechanism in addition to building significant tools to further pave the way for future studies to elucidate how cytoskeletal motors function to organize cellular cargos.
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    Cold War Bohemia: Literary Exchange between the United States and Czechoslovakia, 1947-1989
    (2016-05-13) Goodman, Brian Kruzick; Menand, Louis; Stauffer, John; Bolton, Jonathan; Dimock, Wai Chee
    After the onset of the Cold War, literature and culture continued to circulate across the so-called Iron Curtain between the United States and the countries of the Eastern bloc, often with surprising consequences. This dissertation presents a narrative history of literary exchange between the US and Czechoslovakia between 1947 and 1989. I provide an account of the material circulation of texts and discourses that is grounded in the biographical experiences of specific writers and intellectuals who served as key intermediaries between Cold War blocs. Individual chapters focus on F. O. Matthiessen, Josef Škvorecký, Allen Ginsberg, and Philip Roth, and I discuss the transmission of literary works by writers like Franz Kafka, Ernest Hemingway, Langston Hughes, Ludvík Vaculík, and Milan Kundera. I also discuss a range of institutions—from literary magazines and book series to universities and government censors—that mediated the circulation of literature between the US and Czechoslovakia. To reconstruct this history, I draw on a multilingual archive of sources that includes transnational correspondence, secret police files, travelogues, and samizdat texts. A central argument of “Cold War Bohemia” is that the transnational circulation of literature produced new lines of countercultural influence across the Iron Curtain. By the 1970s and 1980s, literary exchange also helped constitute a network of writers and intellectuals who promoted new discourses about the relationship between literature, dissent, and human rights. The literary counterculture that emerged between the US and Czechoslovakia took on many local and contingent forms, but in each case, the circulation of literature allowed a new transnational public to imagine an alternative world beyond Cold War boundaries.