So Cal Bio Research Scientists Unlock Metabolic Secrets of Biological Clock
Anyone who's ever pulled an all-nighter to finish a project knows how it wreaks havoc with your metabolism. The fact is, it's not just a nicety to be awake and active during the day and sleep at night: it's the way bodies are hard-wired. Scientists have long-suspected that upsets in a person's biological clock could play a factor in the development of metabolic disorders like diabetes. Now a team of researchers from three Southern California universities has made surprising discoveries that support that hypothesis. Not only have they isolated the protein that regulates the biologic clock (and named it cryptochrome), but they have found a molecule called KL001 that dictates when cryptochrome gets sent to the proteasome recycling bin. Which is to say, they now know a lot more about this complex circadian system that not only tells the body when to sleep and wake, but also how the body should manage glucose levels in those periods of relative activity and dormancy. The bio research study was published in the July 13 advance online issue of the journal Science.
[Graphic by Peter Allen, University of California, Santa Barbara]
Dr. Steve Kay is a biologist and incoming dean of the University of Southern California Dornsife College of Letters, Arts and Sciences. He'll be making that move in the fall up the coast from his current appointment as a lab director and dean at UCSD. It was at UCSD that Kay's Lab made major strides understanding the subtle mechanism of circadian rhythms, with profound implications. Their work is elegantly described in the Kay Lab abstract:
Our Laboratory studies the composition and architecture of circadian networks in plants and animals. These networks are thought to provide adaptive advantages to organisms, and are now known to be pervasive in the integration with many other regulatory modules in multiple cell types. We employ high throughput genomics and chemical biology pipelines to identify network components and apply mechanistic approaches to understand their detailed function and interactions. In both plant and animal systems we have found that circadian networks are hierarchical and composed of regulatory layers that act at the transcriptional and posttranscriptional levels. Increasingly we are finding that circadian regulation is tightly integrated with metabolic networks, and operate with reciprocal regulatory interactions.
After Dr. Kay's lab research isolated KL001, they called on colleagues working in biological chemistry at the Scripps Research Institute in La Jolla to help them better understand chemically how it interacted with other regulatory molecules, specifically cryptochrome. The result:
“Those biochemical studies showed us that KL001 prevents cryptochrome from being degraded by the proteasome system, which was another big surprise,” Kay said. “It essentially interferes with the signal to send cryptochrome to the garbage can.”
Building on that new information, they next turned to UCSB chemical engineer Frank Doyle and his lab group to plot the mechanics of the KL001-chryptochrome function. Of that collaboration Kay gratefully acknowledges:
“They constructed a beautiful mathematical model of cryptochrome’s role in the clock. That model was essential in allowing us to understand the action of the compound because the biological clock is very complicated. It’s like opening the back of a Rolex and seeing the hundreds of tiny little cogs that are tightly integrated.”
The NSF just released a report titled Collaboration in Academic R&D: A Decade of Growth in Pass-Through Funding, noting that the amount of money passed on to other institutions to support joint participation in research studies has grown significantly in the past decade. They attribute this rise to Federal initiatives favoring research collaboration, technological advances that facilitate communication, and opportunities for division of labor, risk sharing, and increased research credibility. The joint effort between UCSD, Scripps, UCSB, and now USC (where Kay's Lab is moving, and where this valuable research will certainly continue), is a testament to the productivity of the collaborative model.
Biotechnology Calendar, Inc. will be holding its 7th annual USC BioResearch Product Faire FrontLine event on the Health Sciences campus October 3, 2012. This professional show is an excellent opportunity for life scientists and lab equipment specialists to come together and discuss lab technologies to make every lab run at its best. The USC Health Sciences event is one of three BCI tradeshows held over a three-day period in the greater Los Angeles area:
- 10/02/2012 -- 12th Annual BRPF event, UC Irvine
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- 10/04/2012 -- 29th Semiannual BVS event, UCLA
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