* They have a strain of C.Elegans worms that have engineered to develop Alzheimer's within 5 days of birth.
* They will develop lasers and microfluidics to monitor the worms in real time to instantly detect when one of millions of drugs is repairing neurons
* This will greatly speed up the search for drugs that may delay or prevent neurodegeneration in humans.
* It will also accelerate developing an improved understanding of aging.
A challenge to understanding aging and development of degenerative diseases is that new technology is needed to directly characterize how neuronal proteins are distributed across the entire nervous system over time, and how specific neurons degenerate and are malformed with age. A second huge barrier to preventing or treating diseases like Alzheimer's disease is the amount of time it takes to identify drugs that work effectively. Typically, drugs are tested on mice — a process that is expensive and requires one to two years for mice to age while testing just a few dozen drugs at a time.
With the NIH grant, Ben-Yakar, Pierce-Shimomura and a team of students aim to eliminate both hurdles by developing an automated system that rapidly reduces the time and cost of drug testing. Instead of mice, the researchers will use a short-lived, 1 mm-long worm, known as C. elegans, to test the effectiveness of millions of drugs.
Despite having only 302 neurons compared to the billions of neurons in the human brain, the worms have a genetic makeup similar to humans – making them prime for testing drugs.
Researchers in Pierce-Shimomura’s lab engineered a new strain of worm that develops Alzheimer’s disease. Just as in humans, a subset of the worm’s brain degenerates in “middle age” – which conveniently is only 5-days-old in the tiny worms. The dying neurons can be visualized easily through the transparent body. The researchers have recently discovered that candidate drugs for treating human Alzheimer’s disease also prevent the death of neurons in their worm model. This result provides the basis to use their worm model to search for new drugs that may delay or prevent neurodegeneration in humans.
It will be up to Ben-Yakar to develop the novel optical techniques and microfluidic devices capable of determining — within a matter of seconds — which drugs are effective at repairing or regenerating neurons within the worms.
Ben-Yakar, whose engineering feats already include developing a precise laser nanosurgery for nerve regeneration studies in C. elegans and the first laser microscalpels capable of removing cancerous cells without damaging neighboring cells, said the worms will be genetically engineered to have color-coded neurons with florescent probes. Neurons in the worm that emit a strong florescent signal will indicate that the specific neurons in the worm are healthy and that the drug being tested is working.
“Using Adela’s microfluidic system, we will automate the monitoring of the nervous system, enabling us to test how millions of candidate medicines might prevent or delay neurodegeneration,” said Pierce-Shimomura, an assistant professor in the Section of Neurobiology. "A drug screen of this size has never been attempted."
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