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Single-Cell Biophysics: Measurement, Modulation, and Modeling
Monday Speaker Abstracts
29
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.