Single-Cell Biophysics: Measurement, Modulation, and Modeling

Single-Cell Biophysics: Measurement, Modulation, and Modeling

Monday Speaker Abstracts

Chromosomes as Single Molecules Sunney Xie 1,2 . 1 Harvard University, Cambridge, MA, USA, 2 Peking University, Beijing Advanced Innovation Center for Genomics, Beijing, China. Since the 1990s, developments in room-temperature single-molecule spectroscopy, imaging, and manipulation have allowed studies of single-molecule behaviors in vitro and in living cells. Unlike conventional ensemble studies, single-molecule enzymology is characterized by ubiquitous fluctuations of molecular properties. The understanding of such single-molecule stochasticity is pertinent to many life processes. Applications of single-molecule technologies to biology and medicine have become a major force in life sciences. DNA exists as single molecules that carry genetic codes in each individual cell. For this reason, gene expression is stochastic, i.e probabilistic. Single-molecule gene expression experiments in live single cells have allowed quantitative description and mechanistic interpretations. The fact that there are 46 different individual DNA molecules (chromosomes) in a human cell and each chromosomal DNA has a different nucleotide sequence, dictates that genomic variation occurs stochastically and cannot be synchronized among individual cells. In fact, every germ cell of an individual is different because of recombination, and cancer cells in a primary tissue are highly heterogeneous because of drastic genome changes such as single- nucleotide variations and copy-number variations. Because these genomic changes in a single cell occur stochastically, different cells cannot be synchronized. Consequently, single-cell measurements are necessary, yet they have been hampered by technical difficulties. It is only recently that single-cell single-molecule measurements have been made possible, thus creating opportunities to investigate and diagnose cancer, and to avoid genetic disorders in newborns.

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