A new set of technologies for controlling the aggregation of proteins in living cells could aid the search for cures for Alzheimer’s disease, amyotrophic lateral sclerosis (ALS) and other neurodegenerative conditions. The methods also have potential for a host of other biotechnology applications requiring the control of protein assemblies.
The technologies build on a new paradigm in intracellular organization: Living matter, including the proteins inside cells, can self-organize by condensing into liquid droplets and gels.
These “phase transitions” in living organisms are part of normal functioning, but they can go awry and cause cellular dysfunction and disease, said Clifford Brangwynne, an associate professor of chemical and biological engineering, a Howard Hughes Medical Institute investigator, and a pioneer in this area of research.
Brangwynne and his team have developed methods to screen for new drug compounds to treat diseases that involve faulty protein organization. One of these tools, called optoDroplet, uses blue laser light to control the interactions between proteins. Researchers can fire a laser into a precise area of the cell to trigger proteins to cling to each other.
By varying the intensity of the light, the researchers can prompt the proteins to cluster into liquid-like droplets, which over time can mature into solid-like aggregates, mimicking what occurs in neurodegenerative diseases like ALS. The tools recently developed by the team can help researchers learn more about protein interactions and how to control them to restore human health.
“The study of phase transitions in living cells is a growing new field, but until now there have been limited ways to monitor and control these transitions. Our tools allow researchers to study and manipulate these processes in living cells.”
-Clifford Brangwynne, Associate Professor of Chemical and Biological Engineering
Team members: Dan Bracha, postdoctoral research fellow, and Yongdae Shin, former postdoctoral research associate
Collaborators: Mikko Haataja, professor of mechanical and aerospace engineering; Michael Levine, the Anthony B. Evnin ’62 Professor in Genomics; Jared Toettcher, assistant professor of molecular biology
Development status: Patent protection is pending. Princeton is seeking outside interest for the further development of this opportunity.
Funding: National Institutes of Health, Defense Advanced Research Projects Agency, Howard Hughes Medical Institute
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