KillerRed illuminates neurons

A new Yale-led study may help scientists develop novel treatments for neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases.

The team developed a new fluorescent protein called KillerRed that reveals how neurons in roundworms respond to damage. The study, which was published in the journal Cell Reports on Oct. 31, found that cells affected by KillerRed generated the same molecules produced by various neurodegenerative disorders.

“One of the biggest challenges in biology is the real time and precise manipulation of single cells in vivo,” Yale professor of cell biology Daniel Colon-Ramos, who was not involved in the study, said in an email to the News. “In recent years we have seen great progress on this topic. [This] study adds to this important repertoire.”

KillerRed causes neurons to produce the same toxic molecules generated by neurodegenerative diseases. The researchers found that certain neurons are resistant to KillerRed activation, which suggests that these neurons have a better ability to resist these toxic chemicals and potentially the effects of neurodegenerative disease.

The research team, which included investigators from Yale, Harvard, University of Queensland in Australia and Georgia Tech, sought to alter the way that neuron circuits work in a way researchers could easily analyze in the lab, said study lead author Hang Lu, a professor at Georgia Tech’s School of Chemical and Biomolecular Engineering. The KillerRed protein allows researchers to kill specific groups of neurons and observe the resulting changes in brain circuits and in behavior.

KillerRed has already had a positive impact on the research at Yale labs. Yale professor of molecular biophysics and biochemistry Michael Koelle said the protein represents a significant advance in the field of optogenetics, which uses biomedical engineering techniques and optical technology to manipulate the activity of neurons. Koelle, who has already used the technique in his lab, said KillerRed enables scientists to kill otherwise unharmed neurons and examine them in isolation before the body starts adapting to the effects of neuronal damage.

“The lab has really worked out all the necessary technical details to get the technology working well and has really validated that the technology works well, quickly, and in many types of neurons,” Koelle wrote in an email to the News.

Lu said she is optimistic KillerRed will play a significant role in future research, as the technique can help reveal how neurons change during development, how they contribute to behavior and how they change with age and disease.

According to the Alzheimer’s Association, one in eight older Americans suffers from Alzheimer’s disease.

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