From the time we eat breakfast to when we leave work,
mechanical clocks control a large part of our lives. But we, and other
creatures, also have biological clocks that regulate just about every function
in our bodies.
Scientists know our biological clocks are coordinated—from
our daily rhythms to our metabolism, and the growth, development, and death of
cells—but they aren't sure how. Using a $14 million grant from DARPA, the
Defense Advanced Research Projects Agency, a team of biologists and
mathematicians at Duke and other universities will be looking more closely at
the timepieces that drive life.
"Biological systems have amazing timing
capabilities," says Duke mathematician John Harer, the lead investigator
on the new grant. The body and its individual cells form an intricate machine,
with complex timing mechanisms, which often work flawlessly and usually repair
themselves when they don't, he says.
Harer and his collaborators want to unwind the variety of
biological clocks found in cells, looking closely at their pieces to see how
they work individually and how they work together. Scientists have studied how
day and night affects animals' and plants' circadian rhythms, how cells divide,
live and die and how they control their own metabolism and growth, Harer says.
But, it's been much more challenging to understand how these
and other processes in cells relate to one another and how they work within
life's larger rhythms. The researchers wonder whether there are universal rules
controlling such cyclic behavior.
With the DARPA grant, Harer has assembled some of the
world's leading experts on the cell cycle, the circadian clock, the metabolism
of yeast, root growth in plants, and pulsing processes in bacteria, to deconstruct
the molecular and genetic rhythms that keep these organisms alive.
One of the most challenging goals is to identify the
specific genes that turn each type of biological clock on and off and what
signals those genes send with each on-off switch, Harer says. The other
challenge is to identify what role each gene plays in the clock and whether it
would be a good indicator of the position of that clock in its cycle. They
might, for example, find a gene that controls the circadian clock, and then study
it further to find out whether it's six in the morning or six at night, according
to that organism's clock.
If scientists can isolate the genes, molecules, and signals
of these different biological clocks, they could find ways to control and
repair them if they are broken or damaged, Harer says. They could then use that
information to better understand and control specific groups of cells,
organisms, and possibly even systems within our bodies. Harer says scientists
may also be better able to explain a variety of other observations, such as the
connection between sleep problems and cancer.
One specific DARPA application would be to adjust soldiers'
biological clocks when they travel, to speed recovery from jetlag or slow down
their metabolism after an injury. There's also interest in the signals that
genes and cells send to each other, despite a lot of noise from their
surroundings. If scientists can figure out how timing signals are sent, that
could be useful for improving the way we send, receive and decipher our own
communication signals, Harer says.
Under the new grant, he and his colleagues have four years
to investigate the diverse rhythms of life. DARPA will be checking in along the
way, but ultimately the agency is looking for the scientists to write the
equivalent of sheet music for life's rhythms and then be able to use the notes
to identify the clocks of previously unstudied organisms.
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