Featured Research

from universities, journals, and other organizations

Powerful tool to measure metabolites in living cells

Date:
March 8, 2012
Source:
NewYork-Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Summary:
By engineering cells to express a modified RNA called "Spinach," researchers have imaged small-molecule metabolites in living cells and observed how their levels change over time. Metabolites are the products of individual cell metabolism. The ability to measure their rate of production could be used to recognize a cell gone metabolically awry, as in cancer, or identify the drug that can restore the cell's metabolites to normal.

Imaging S-adenosylmethionine in cells with RNA. The fluorescence markedly increases at each time point after adding methionine (bottom right).
Credit: Image courtesy of NewYork-Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College

By engineering cells to express a modified RNA called "Spinach," researchers have imaged small-molecule metabolites in living cells and observed how their levels change over time. Metabolites are the products of individual cell metabolism. The ability to measure their rate of production could be used to recognize a cell gone metabolically awry, as in cancer, or identify the drug that can restore the cell's metabolites to normal.

Researchers at Weill Cornell Medical College say the advance, described in the March 9 issue of Science, has the potential to revolutionize the understanding of the metabolome, the thousands of metabolites that provide chemical fingerprints of dynamic activity within cells.

"The ability to see metabolites in action will offer us new and powerful clues into how they are altered in disease and help us find treatments that can restore their levels to normal," says Dr. Samie R. Jaffrey, an associate professor of pharmacology at Weill Cornell Medical College. Dr. Jaffrey led the study, which included three other Weill Cornell investigators.

"Metabolite levels in cells control so many aspects of their function, and because of this, they provide a powerful snapshot of what is going on inside a cell at a particular time," he says.

For example, biologists know that metabolism in cancer cells is abnormal; these cells alter their use of glucose for energy and produce unique breakdown products such as lactic acid, thus producing a distinct metabolic profile. "The ability to see these metabolic abnormalities can tell you how the cancer might develop," Dr. Jaffrey says. "But up until now, measuring metabolites has been very difficult in living cells."

In the Science study, Dr. Jaffrey and his team demonstrated that specific RNA sequences can be used to sense levels of metabolites in cells. These RNAs are based on the Spinach RNA, which emits a greenish glow in cells. Dr. Jaffrey's team modified Spinach RNAs so they are turned off until they encounter the metabolite they are specifically designed to bind to, causing the fluorescence of Spinach to be switched on. They designed RNA sequences to trace the levels of five different metabolites in cells, including ADP, the product of ATP, the cell's energy molecule, and SAM (S-Adenosyl methionine), which is involved in methylation that regulates gene activity. "Before this, no one has been able to watch how the levels of these metabolites change in real time in cells," he says.

Delivering the RNA sensors into living cells allows researchers to measure levels of a target metabolite in a single cell as it changes over time. "You could see how these levels change dynamically in response to signaling pathways or genetic changes. And you can screen drugs that normalize those genetic abnormalities," Dr. Jaffrey says. "A major goal is to identify drugs that normalize cellular metabolism."

This strategy overcomes drawbacks of the prevailing method of sensing molecules in living cells using green fluorescent protein (GFP). GFP and other proteins can be used to sense metabolites if they are fused to naturally occurring proteins that bind the metabolite. In some cases, metabolite binding can twist the proteins in a way that affects their fluorescence. However, for most metabolites, there are no proteins available that can be fused to GFP to make sensors.

By using RNAs as metabolite sensors, this problem is overcome. "The amazing thing about RNA is that you can make RNA sequences that bind to essentially any small molecule you want. They can be made in a couple of weeks," Dr. Jaffrey says. These artificial sequences are then fused to Spinach and expressed as a single strand of RNA in cells.

"This approach would potentially allow you to take any small molecule metabolite you want to study and see it inside cells," Dr. Jaffrey says. He and his colleagues have expanded the technology to detect proteins and other molecules inside living cells.

He adds that uses of the technology to understand human biology can be applied to many diseases. "We are very interested in seeing how metabolic changes within brain neurons contribute to developmental disorders such as autism," Dr. Jaffrey says. "There are a lot of opportunities, as far as this new tool is concerned."

Co-authors of the study include Dr. Jeremy S. Paige, Mr. Thinh Nguyen Duc, and Dr. Wenjiao Song from the Department of Pharmacology at Weill Cornell Medical College.

The study was funded by the National Institute of Biomedical Imaging and Bioengineering of the NIH, and the McKnight Foundation. The Cornell Center for Technology Enterprise and Commercialization (CCTEC), on behalf of Cornell University, has filed has filed for patent protection on this technology. Dr. Samie Jaffrey is the founder and scientific advisor to Lucerna Technologies, and holds equity interests in this company. In addition, Lucerna Technologies has a license that is related to technology described here.


Story Source:

The above story is based on materials provided by NewYork-Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. S. Paige, T. Nguyen-Duc, W. Song, S. R. Jaffrey. Fluorescence Imaging of Cellular Metabolites with RNA. Science, 2012; 335 (6073): 1194 DOI: 10.1126/science.1218298

Cite This Page:

NewYork-Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College. "Powerful tool to measure metabolites in living cells." ScienceDaily. ScienceDaily, 8 March 2012. <www.sciencedaily.com/releases/2012/03/120308143111.htm>.
NewYork-Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College. (2012, March 8). Powerful tool to measure metabolites in living cells. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2012/03/120308143111.htm
NewYork-Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College. "Powerful tool to measure metabolites in living cells." ScienceDaily. www.sciencedaily.com/releases/2012/03/120308143111.htm (accessed July 23, 2014).

Share This




More Plants & Animals News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Stone Fruit Listeria Scare Causes Sweeping Recall

Stone Fruit Listeria Scare Causes Sweeping Recall

Newsy (July 22, 2014) The Wawona Packing Company has issued a voluntary recall on the stone fruit it distributes due to a possible Listeria outbreak. Video provided by Newsy
Powered by NewsLook.com
Michigan Plant's Goal: Flower and Die

Michigan Plant's Goal: Flower and Die

AP (July 22, 2014) An 80-year-old agave plant, which is blooming for the first and only time at a University of Michigan conservatory, will die when it's done (July 22) Video provided by AP
Powered by NewsLook.com
Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Newsy (July 22, 2014) The 83 new genetic markers could open dozens of new avenues for schizophrenia treatment research. Video provided by Newsy
Powered by NewsLook.com
CDC Head Concerned About a Post-Antibiotic Era

CDC Head Concerned About a Post-Antibiotic Era

AP (July 22, 2014) Sounding alarms about the growing threat of antibiotic resistance, CDC Director Tom Frieden warned Tuesday if the global community does not confront the problem soon, the world will be living in a devastating post-antibiotic era. (July 22) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins