method doesn’t kill the cells because
information is captured from the outside, on the glass plate.
Love is applying this interrogation
method to ask questions that are relevant
to chronic diseases such as HIV, autoim-munity, cancer and allergies. One ongoing study tracks how allergic patients
become desensitized to milk allergens,
measuring how the patients’ white blood
cells respond to milk extracts. The study
looks at how many cells are responding,
what kinds of immune proteins are being
produced and how much of each protein
is produced by each cell.
By analyzing large numbers of single
events and interactions between small
groups of cells in concert, Love can spot
rare types of cells and events that are
linked to disease. Certain T cells and B
cells found in diseases like multiple sclerosis or diabetes, for example, typically
are present at rates of 1 in 10,000 to 1 in
100,000 of the circulating T cells in a
blood sample, he says. Without looking
at many, many cells, he wouldn’t be able
to spot or study the interactions of these
rare types.
“Single-cell analysis is a bit of a misnomer in the sense that you’re not really
looking at one cell,” Love says. “You’re
resolving to one cell, but you are needing to look at thousands, if not tens or
hundreds of thousands, of cells to understand what that individual measurement
looks like in relation to the rest of the
distribution.”
Single microbes
Studies of cell-to-cell differences also
promise to reveal new information
about single-celled organisms. For a long
time, biologists thought that members
of a microbe colony were all basically
the same, and that those cloned from a
single cell, because they were genetically
identical, should react to environmental
challenges in the very same way.
Scientists now know that individual
traits may, in fact, serve as drivers to boost
the robustness and resistance of microbial populations, says Michael Konopka,
a biochemical engineer at the University
of Washington in Seattle. In the October
2010 issue of Nature Chemical Biology,
he and coauthor Mary Lidstrom outlined
how some members of a microbial colony
will stop growing in times of stress, moving into a dormant state that allows them
to ride out the bad conditions while their
neighbors perish.
Understanding how individuals adapt
to environmental conditions, such as
temperature fluctuations, could help
engineers find ways to boost certain
types of chemical processes used in
manufacturing, Konopka says. Some
naturally occurring microbes, for example, may have a built-in capacity to do
the chemical reactions that industrial
researchers want to perform.
Others research teams are developing
ways to determine the complete genetic
blueprint of single-celled organisms to
get insight into whole populations of cells
that are otherwise difficult to study. Stanford University scientists working under
the direction of Stephen Quake are plucking single cells from populations found in
pond scum, soil or even plaque on teeth,
to ask a seemingly simple question: Who
are you?
Conventional genetic analysis techniques require a large, pure sample
of the microbes, says Paul Blainey, a
postdoctoral researcher in Quake’s lab.
“That usually requires that you’re able to
isolate the particular organism and grow
up a whole huge beaker of it in the lab.”
Unfortunately, the chemical reaction
used to amplify tiny amounts of DNA is
notoriously prone to contamination.
To get around this problem, the Stanford group is using a laser tweezer to sort
individual microbes inside tiny, automated devices designed to analyze minute traces of DNA. Enclosed within this
miniature lab, microbes and their DNA
are safe from contaminants.
In 2007, Quake’s group analyzed the
genome of a single bacterium found
in dental plaque taken from a person’s
mouth. This year the team turned to a
less familiar class of single-celled organisms, the Archaea: Online February 22
in PLoS One, the researchers published
findings on the genome of a single-celled
ammonia-eater from San Francisco Bay.
Developed at the University of British
Columbia, this microchip allows the
simultaneous analysis of 300 cells.
Genetic information gleaned from
an individual microbe, combined with
findings on cell-to-cell differences in
behavior, may provide new insights into
the thousands of unknown or barely
known populations found in water and
soil. Such insight could in turn offer
clues to how microbes act as infectious
agents and how they develop resistance
to antibiotics.
Despite recent gains in studying single
cells and how they differ, there’s much
work to be done, Allbritton says. Current techniques still allow only a small
number — fewer than two dozen — of
the thousands of molecular components
that float around in cells to be measured
at one time.
“It’s embarrassing,” she says. “We’ve
made a lot of progress, but you can see
how far we have to go.”
With such a small subset of cellular
components under study, scientists’
perception of how cells operate may be
colored by what they see, she adds. The
big push now is to develop ways to mea-
sure more of the cell’s contents, and see
how they change over time and work in
relationship to each other.
“If we can see everything,” Allbritton
says, “it might dramatically change how
we view the single cell.” s
Explore more
s Altschuler and Wu lab: www4.
utsouthwestern.edu/altschulerwulab
www.sciencenews.org
October 8, 2011 | SCIENCE NEWS | 29