 |
PAGE 3 OF 3
It takes two copies of human alpha-synuclein gene to make yeast sick and die. To find out which yeast genes could rescue them, researchers in the lab of Susan L. Lindquist, of the Whitehead Institute for Biomedical Research and the Massachusetts Institute of Technology (MIT), devised a “screening platform.”
To find out which yeast genes could rescue them, researchers in the lab of Susan L. Lindquist, of the Whitehead Institute for Biomedical Research and the Massachusetts Institute of Technology (MIT), devised a “screening platform.”
They used a new library of individual yeast genes and deposited them one by one in 96-well plates. With the aid of a high-throughput device, a robot stamped a small amount of yeast into each well, already spiked by the researchers with an essential ingredient for yeast growth. Next, the robot dropped a different, additional gene into each well, working through the yeast genome, one gene per well. If the yeast in the wells started dividing, researchers knew it had taken up the extra gene.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
A Yeast Screen to Discover Modifiers of α-synuclein Toxicity
 Download PDF (PDF, 179KB)
|
|
|
|
|
|
|
|
|
|
Finally, the robot put the growing colonies on food-filled dishes with a special sugar that turned on the alpha-synuclein genes, which had been silent until then.
Normally, most yeast would stop dividing and die. Those that lived provided the clues that may eventually help people with Parkinson’s disease. In the case of the Lindquist lab’s study, more of the yeast with extra copies of the ER-Golgi trafficking pathway genes survived.
Using this same screening platform, the researchers have tested various small molecules (substituted for individual genes in the wells) to test potential therapies; at this writing, they have screened more than 150,000 small molecules secured from other collaborators. FoldRx Pharmaceuticals, Inc., a company Lindquist started three years ago, has licensed the yeast-screening platform and is screening proprietary molecules for activity against Parkinson’s disease. The platform is available to interested researchers through a material transfer agreement with MIT.
—C.C.M.
|
|
|
Back
