Posted on 12/09/2021 4:29:37 PM PST by nickcarraway
Life is organized on a 24-hour schedule. Central to this regular rhythm is the circadian clock, timekeepers that are present in virtually every organ, tissue and cell type. When a clock goes awry, sleep disruption or a variety of diseases can result.
A recent Northwestern University discovery could help in understanding how this clock is linked to daily cycles. A team of neurobiologists has identified a new gene, called Tango10, that is critical for daily behavioral rhythms. This gene is involved in a molecular pathway by which the core circadian clock (the “gears”) controls the cellular output of the clock (the “hands”) to control daily sleep-wake cycles.
While the study was done using the fruit fly Drosophila melanogaster, the findings have implications for humans. Knowledge of how this pathway works could lead to therapeutics to help sleep problems and could shed light on clock-related human diseases, such as depression, neurodegenerative disease and metabolic disease.
“Scientists know a lot about the clock’s ‘gears’ but not so much about the ‘hands,’ where the behavior is produced, or the connection between the two,” said Dr. Ravi Allada, a circadian rhythms expert who led the study.
“We wanted to better understand the molecular underpinnings of the daily ‘wake-up signal,’ which alerts an animal it’s time to awake,” he said. “In this study, we focused on pacemaker neurons that control the sleep-wake cycle and used genetic screening to identify genes that regulate the neurons.”
Allada is the Edgar C. Stuntz Distinguished Professor in Neuroscience and chair of the neurobiology department in the Weinberg College of Arts and Sciences. Allada also is associate director of Northwestern’s Center for Sleep and Circadian Biology.
The study was published by the Proceedings of the National Academy of Sciences (PNAS). Allada is the corresponding author of the paper.
In addition to the fly experiments conducted in Allada’s lab, the Northwestern team worked with Casey Diekman and Matthew Moyeat the New Jersey Institute of Technology who performed computational modeling experiments.
The Northwestern researchers screened a number of genes they thought could be important for the circadian clock’s operation and behavior of the fly. Through this process, they discovered the gene called Tango10. When they knocked out this gene, the fly lost its normal 24-hour rhythm of behavior. Certain potassium currents were reduced and likely resulted in hyperactive neurons and contributed to a loss of regular rhythm.
Under normal conditions in the fly, the levels of Tango10 protein go up and down with circadian time which can modulate the activity of the neurons to go up and down, which in turn can drive the animal’s sleep-wake cycle and behavior. In flies that lack the Tango10 gene, this daily rhythm is disrupted.
“Our findings fill a molecular gap in our understanding of how the core gears of the clock control the hands,” Allada said.
The title of the paper is “The E3 ubiquitin ligase adaptor Tango10 links the core circadian clock to neuropeptide and behavioral rhythms.” The co-first authors are Jongbin Lee and Chunghun Lim, former postdoctoral fellows in Allada’s lab.
1. Jongbin Lee, Chunghun Lim, Tae Hee Han, Tomas Andreani, Matthew Moye, Jack Curran, Eric Johnson, William L. Kath, Casey O. Diekman, Bridget C. Lear, Ravi Allada. The E3 ubiquitin ligase adaptor Tango10 links the core circadian clock to neuropeptide and behavioral rhythms. Proceedings of the National Academy of Sciences, 2021; 118 (47): e2110767118 DOI: 10.1073/pnas.2110767118
Node Smith, ND is a naturopathic physician in Humboldt, Saskatchewan and associate editor and continuing education director for NDNR. His mission is serving relationships that support the process of transformation, and that ultimately lead to healthier people, businesses and communities. His primary therapeutic tools include counselling, homeopathy, diet and the use of cold water combined with exercise. Node considers health to be a reflection of the relationships a person or a business has with themselves, with God and with those around them. In order to cure disease and to heal, these relationships must be specifically considered. Node has worked intimately with many groups and organizations within the naturopathic profession, and helped found the non-profit, Association for Naturopathic Revitalization (ANR), which works to promote and facilitate experiential education in vitalism.
I’m of the understanding that shift workers live 7 years fewer.
How will this knowledge help POTUS Plugs and his Sundowners problem?
Node Smith—now there is name everyone should envy! Hopefully he hasn’t created multiple other nodes, one can only have so many nodes.
Time devours our feeble mortality, leaving us with but the sour residue of memory.
Lots of nodes in my Circuits class...
Let me know when they have knowledge that can be applied.
Usually if you have a job that requires you to work in shifts, you're more likely to be less educated and have other habits (smoking, drinking, unhealthy diet) that would be likely to decrease your lifespan. So I'm not sure if they've determined that shift work directly shortens your life. I'd like to know since I have worked in shifts for most of my career.
I would like to know as well. I worked shift duty in the USAF, and currently do storm duty for the electric utility company.
Certainly we will need this kind of gene therapy if we are to survive on other planets.
I feel confident that this research could never be used for evil by anyone ever.
I was lucky. When I was a rookie cop I did the 4x12 shift so I never did straight-up midnights. Those guys were zombies. And we’d get off work at midnight and go straight to the bars that closed at 4am, which is why everyone called it the “4x4” shift. Haha.
I worked 1800-0600. Weekends were Tuesday, Wednesday, and every other Thursday.
0700 on a Tuesday morning we were drunk, wrestling in the hallways, and playing pool.
Normal Airman were like WTF!?!?
“I feel confident that this research could never be used for evil by anyone ever.”
I’m glad we, and every SciFi writer ever, are on the same page...
I’ve worked ROTATING shift work for the last 31 years retiring in 2008.
Worst possible shifts at that. Midnights, evenings, days 10 days straight with 4 days off in between.
Then they went to 12 hour days rotating shifts which really messed me up.
Yet at the age of 75 I have outlived my dad by 5 years, who, in the last 20 years of his life worked only a day shift.
I certainly hope you have many more.
I’m sure you know, statistically speaking, N=2 is not a decent sample size.
My dad had 3 brothers and two sisters. The only non smoker/drinker died first. The whiskey swilling, 2 pack a day smoker outlived everyone...
And thus my genetic tendency of being a night owl is revealed....finally....
2-3Am to bed 10-12 wakeup is my natural cycle....has been forever and a day....used to lay awake in my bed as a teen every night just thinking about stuff for hours on end because I couldn’t sleep and my brother was in the next bed so I couldn’t turn the light on to read or I’d wake him.
In the Navy (decades past now) my favorite watch was the mid-watch 1) because I got mid rats right before hand, but 2) because it felt right to be in charge (OOD) while nearly everyone else was zonked.
ah well... in retirement I’ll be able to let nature take it’s proper course.
So, that’s it...my TANGO10 is broken.
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.