A Johns Hopkins researcher played a leading role in
the creation of a landmark map detailing the way proteins
interact within fruit fly cells. The map provides a model
for future studies in humans that should lead to a better
understanding of genetic disorders and infectious diseases.
The research also opens an important new door toward
identifying drugs for treatment of such ailments. The paper
was published online by the journal Science at the
Science Express
Web site on Nov. 6.
Earlier research had provided a list of the 14,000
genes within a fruit fly and the proteins they produce
within the insect's cells. "That's like having a biological
'parts' list," said
Joel S.
Bader, an assistant professor in the
Department of Biomedical
Engineering. "But what we haven't known is how these
parts are connected to one another. We haven't had the
equivalent of a wiring diagram or an assembly manual. What
this new map does is tell us which proteins 'talk' to one
another and work together within the cell. We've only had
maps like this for single-cell organisms like yeast. This
is significant because it's the first large-scale assembly
diagram for a multicellular organism."
With more than three dozen colleagues, Bader began
working on the map several years ago as director of
bioinformatics at CuraGen Corp., a biotech firm based in
New Haven, Conn., where most of the re-search was carried
out. He continued working on the project after joining the
faculty of the
Whitaker Biomedical Engineering Institute at Johns
Hopkins in August. Bader is one of three lead authors of
the Science paper detailing the protein interaction map. He
said the map produced for the fruit fly, or Drosophila
melanogaster, can serve as a template that can be followed
for other species, including human beings.
"This is a milestone because one of the things that's
been missing from the advances in genome sequencing is that
we haven't known what each gene does," Bader said. "It's
not enough to know which parts make up a human cell. You
have to know which parts work together to carry out
particular functions within the cell. This will lead to a
better understanding of genetic diseases, and it will add
to our knowledge of basic biology, our understanding of how
cells work."
The fruit fly has been a favorite model for genetics
researchers for almost a century because the insects are
small, easily bred and have a generation time of only about
two weeks. Fruit flies and humans share devel-opmental
similarities, and biological processes are even more
similar at the cellular level.
To find out which proteins expressed by fruit flies'
genes interact with others, Bader and his colleagues
employed a technique called the two-hybrid method, in which
they "mated" specific types of yeast cells. In each
experiment, a yeast cell carrying just one fruit fly
protein was mixed with yeast cells carrying about 10,000
other fruit fly proteins. By examining the offspring that
survived this "marriage," the researchers could determine
which proteins interacted with one another. The experiment
had to be repeated 10,000 times to generate enough data to
produce the interaction map. The large research team
included people who conducted the lab experiments, others
who organized the massive amounts of data and still others
— including Bader, a specialist in computational
biology — who analyzed the data.
The results of the fruit fly protein interaction map
research will be stored in databases that will be publicly
accessible to other scientists via Web sites. Bader is
using the map in a collaboration with infectious disease
experts to understand how our cells combat microbial
pathogens. Bader believes other researchers will use the
data to learn more about the workings of living cells and
to locate drug targets that may be useful in the treatment
of illnesses that may have a genetic component, including
cancer, neurological disorders and diabetes.