The new age of bioimaging — Page 3 of 7 <
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DNA-damage
control
A woman lies on the beach on a warm summer day, bathing
her skin in ultraviolet light. A man takes a drag on
a cigarette, filling his lungs with smoke. Although
DNA-damaging agents such as these bombard our cells
every day, proteins heal most of the injuries. A team
of scientists developed a high-throughput system to
probe components of this DNA repair kit during the summer
of 2005.
 |
| Carlos Ríos-Velázquez |
MIT’s Computational and Systems Biology Initiative
(CSBi) supported Professor Carlos Ríos-Velázquez,
who took a three-month sabbatical from the University
of Puerto Rico at Mayagüez to spearhead the effort
as part of an outreach program for minority faculty.
He traveled to Cambridge with graduate student Josué
Malevé-Orengo and undergraduate Alana Toro-Ramos,
and worked in the labs of Rebecca Fry and Leona Samson.
| “Soon we’ll be able to see how the
entire cell reacts to a specific environmental change,”
says University of Puerto Rico professor Carlos
Ríos-Velázquez. “We’ll
have a global view of the response.” |
The team decided to map the concentration and location
of all the yeast proteins that respond to DNA-damaging
agents. Each yeast cell contains about 4,000 genes that
code for proteins, and Ríos-Velázquez
wondered how many play a “detoxifying” role.
His team tapped into a yeast library to investigate
their functions.
 |
| Josué Malevé-Orengo |
|
| Alana Toro-Ramos |
Each “book” in the library consists of a
yeast cell with a modified gene for a particular protein.
When produced, the protein glows green. Ríos-Velázquez
resolved to screen the entire yeast genome by exposing
each book to a DNA-damaging agent and photographing
the results.
Ríos-Velázquez has not yet completed the
screen, but his team tested the procedure and determined
it will work. (They are using a Cellomics Array-Scan
at the Whitehead-MIT center to automate the experiment,
though the microscope works best with mammalian cells,
which are bigger.)
Members doused two strains of yeast cells—books
corresponding to well-studied proteins—with a
potent DNA-damaging agent. Before and after shots revealed
that the proteins responded as expected. One protein
moved from the nucleus to the cytoplasm, and the level
of the other protein increased.
“Soon we’ll be able to see how the entire
cell reacts to a specific environmental change,”
says Ríos-Velázquez. “We’ll
have a global view of the response.”
| Written by Alyssa Kneller |
|
