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Weitz, Charles

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Weitz

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Charles

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Weitz, Charles
Author's Publications: search.filters.isAuthorOfPublication.11faffcd-eead-41ed-8f99-65f8adfd22c8

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    Single-cell analysis of circadian dynamics in tissue explants
    (The American Society for Cell Biology, 2015) Lande-Diner, Laura; Stewart-Ornstein, Jacob; Weitz, Charles; Lahav, Galit
    Tracking molecular dynamics in single cells in vivo is instrumental to understanding how cells act and interact in tissues. Current tissue imaging approaches focus on short-term observation and typically nonendogenous or implanted samples. Here we develop an experimental and computational setup that allows for single-cell tracking of a transcriptional reporter over a period of >1 wk in the context of an intact tissue. We focus on the peripheral circadian clock as a model system and measure the circadian signaling of hundreds of cells from two tissues. The circadian clock is an autonomous oscillator whose behavior is well described in isolated cells, but in situ analysis of circadian signaling in single cells of peripheral tissues is as-yet uncharacterized. Our approach allowed us to investigate the oscillatory properties of individual clocks, determine how these properties are maintained among different cells, and assess how they compare to the population rhythm. These experiments, using a wide-field microscope, a previously generated reporter mouse, and custom software to track cells over days, suggest how many signaling pathways might be quantitatively characterized in explant models.
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    Guidelines for Genome-Scale Analysis of Biological Rhythms
    (SAGE Publications, 2017) Hughes, Michael E.; Abruzzi, Katherine C.; Allada, Ravi; Anafi, Ron; Arpat, Alaaddin Bulak; Asher, Gad; Baldi, Pierre; de Bekker, Charissa; Bell-Pedersen, Deborah; Blau, Justin; Brown, Steve; Ceriani, M. Fernanda; Chen, Zheng; Chiu, Joanna C.; Cox, Juergen; Crowell, Alexander M.; DeBruyne, Jason P.; Dijk, Derk-Jan; DiTacchio, Luciano; Doyle, Francis; Duffield, Giles E.; Dunlap, Jay C.; Eckel-Mahan, Kristin; Esser, Karyn A.; FitzGerald, Garret A.; Forger, Daniel B.; Francey, Lauren J.; Fu, Ying-Hui; Gachon, Frédéric; Gatfield, David; de Goede, Paul; Golden, Susan S.; Green, Carla; Harer, John; Harmer, Stacey; Haspel, Jeff; Hastings, Michael H.; Herzel, Hanspeter; Herzog, Erik D.; Hoffmann, Christy; Hong, Christian; Hughey, Jacob J.; Hurley, Jennifer M.; de la Iglesia, Horacio O.; Johnson, Carl; Kay, Steve A.; Koike, Nobuya; Kornacker, Karl; Kramer, Achim; Lamia, Katja; Leise, Tanya; Lewis, Scott A.; Li, Jiajia; Li, Xiaodong; Liu, Andrew C.; Loros, Jennifer J.; Martino, Tami A.; Menet, Jerome S.; Merrow, Martha; Millar, Andrew J.; Mockler, Todd; Naef, Felix; Nagoshi, Emi; Nitabach, Michael N.; Olmedo, Maria; Nusinow, Dmitri A.; Ptáček, Louis J.; Rand, David; Reddy, Akhilesh B.; Robles, Maria S.; Roenneberg, Till; Rosbash, Michael; Ruben, Marc D.; Rund, Samuel S.C.; Sancar, Aziz; Sassone-Corsi, Paolo; Sehgal, Amita; Sherrill-Mix, Scott; Skene, Debra J.; Storch, Kai-Florian; Takahashi, Joseph S.; Ueda, Hiroki R.; Wang, Han; Weitz, Charles; Westermark, Pål O.; Wijnen, Herman; Xu, Ying; Wu, Gang; Yoo, Seung-Hee; Young, Michael; Zhang, Eric Erquan; Zielinski, Tomasz; Hogenesch, John B.
    Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding “big data” that are conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome-scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them.