Featured Research

from universities, journals, and other organizations

Hopkins Researchers Develop New Tool To Watch Real-time Chemical Activity In Cells

Date:
July 24, 2006
Source:
Johns Hopkins Medical Institutions
Summary:
Attempts to identify potential drugs that interfere with the action of one particular enzyme linked to heart disease and similar health problems led scientists at Johns Hopkins to create a new tool and new experimental approach that allow them to see multiple, real-time chemical reactions in living cells.

The team built a protein biosensor that indicates if an enzyme located nearby is turned on or off. The sensor is made from a protein that glows, originally isolated from jellyfish. When PKA is turned off, the biosensor glows blue. When PKA is turned on and is physically close to a biosensor, PKA itself changes the shape of the biosensor, causing it to glow green instead.
Credit: Image courtesy of Johns Hopkins Medical Institutions

Attempts to identify potential drugs that interfere with the action of one particular enzyme linked to heart disease and similar health problems led scientists at Johns Hopkins to create a new tool and new experimental approach that allow them to see multiple, real-time chemical reactions in living cells. Their report on the work is published July 21 in the journal ACS Chemical Biology.

Most current drug development operations test chemicals on enzymes isolated from their normal environs and then take further steps to see if the chemical can get into the cell to do its work, and figure out how poisonous the chemical is to a cell.

"Living cells are critical to our work because they show us how and what is actually happening in a normal context and time span when a chemical is added," says Jin Zhang, Ph.D., an assistant professor of pharmacology and molecular sciences in Hopkins' Institute for Basic Biomedical Sciences.

Testing chemicals on enzymes in living cells provides the opportunity to find potential drugs that work in new ways. For example, using living cells allows researchers to "see" where in the cell chemicals do their work. Scientists could then design new drugs to go to specific places within cells to work more efficiently. Also, streamlining the one-at-a-time approach offers the chance to study - and rule out or in - many potentially useful chemicals at once.

What Zhang's team developed is a biosensor and simple testing procedure that tells if a particular enzyme - called PKA - that acts like a "switch" is "on" or "off" in a living cell. The group has been focused on trying to understand and interfere with this enzyme switch, because if the enzyme is turned on at the wrong time or at the wrong place within cells, it can lead to cells misbehaving, which ultimately can lead to heart disease.

In the course of their work, the team built a protein biosensor that indicates if an enzyme located nearby is turned on or off. The sensor is made from a protein that glows, originally isolated from jellyfish. When PKA is turned off, the biosensor glows blue. When PKA is turned on and is physically close to a biosensor, PKA itself changes the shape of the biosensor, causing it to glow green instead.

Manipulating the sensor allows the researchers to direct it to specific locales within cells. That allows the researchers to see where in the cell the active enzyme is located. So this PKA sensor not only indicates whether the enzyme is on or off, but also locates where PKA is being turned on or off within the cell. "Proteins aren't spread out evenly in cells," says Zhang, "but tend to cluster together in order to do specific jobs, and we now can see how different clusters are regulated differently."

When the researchers put their new sensor into living mammalian cells growing in the lab, they were able to test the effects of 160 different chemicals at once and see if any of these chemicals could turn on or off the PKA enzyme by looking for green or blue glowing cells.

Of the 160 chemicals tested, three caused cells to turn on the switch and two others caused cells to turn off the switch.

The 160 chemicals tested are from the Johns Hopkins Clinical Compound Library, a collection of about 3,300 chemicals. Most of them are drugs already approved by the U.S. Food and Drug Administration, while others are drugs approved by regulatory agencies in other countries or are other clinically relevant chemicals.

"If we can find a new activity for a known drug, this may lead to a new use or a new way of thinking about that drug," says Zhang, who hopes to test the rest of the chemicals in the collection soon for their ability to interfere with the enzyme tested in this study. Finding a drug that can tame this enzyme could lead to new treatments for heart disease, diabetes, memory disorders and certain cancers, for example.

Zhang says the "high throughput" potential of the sensor may have wide-reaching applications that could be adapted to testing various chemicals to test chemicals for their ability to interfere with other enzymes related to PKA - which as a family are known as kinases - that are widely implicated in diseases and an emerging class of drug targets.

The researchers were funded by the American Heart Association and the National Institutes of Health.

Authors on this paper are: Michael Allen, Lisa DiPilato, Meghdad Rahdar, Yunzhao Ren, Curtis Chong, Jun Liu and Zhang, all of Hopkins.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Cite This Page:

Johns Hopkins Medical Institutions. "Hopkins Researchers Develop New Tool To Watch Real-time Chemical Activity In Cells." ScienceDaily. ScienceDaily, 24 July 2006. <www.sciencedaily.com/releases/2006/07/060721182621.htm>.
Johns Hopkins Medical Institutions. (2006, July 24). Hopkins Researchers Develop New Tool To Watch Real-time Chemical Activity In Cells. ScienceDaily. Retrieved April 17, 2014 from www.sciencedaily.com/releases/2006/07/060721182621.htm
Johns Hopkins Medical Institutions. "Hopkins Researchers Develop New Tool To Watch Real-time Chemical Activity In Cells." ScienceDaily. www.sciencedaily.com/releases/2006/07/060721182621.htm (accessed April 17, 2014).

Share This



More Plants & Animals News

Thursday, April 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Change of Diet Helps Crocodile Business

Change of Diet Helps Crocodile Business

Reuters - Business Video Online (Apr. 16, 2014) Crocodile farming has been a challenge in Zimbabwe in recent years do the economic collapse and the financial crisis. But as Ciara Sutton reports one of Europe's biggest suppliers of skins to the luxury market has come up with an unusual survival strategy - vegetarian food. Video provided by Reuters
Powered by NewsLook.com
Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
Powered by NewsLook.com
Thousands Of Vials Of SARS Virus Go Missing

Thousands Of Vials Of SARS Virus Go Missing

Newsy (Apr. 16, 2014) A research institute in Paris somehow misplaced more than 2,000 vials of the deadly SARS virus. Video provided by Newsy
Powered by NewsLook.com
Raw: Three Rare White Tiger Cubs Debut at Zoo

Raw: Three Rare White Tiger Cubs Debut at Zoo

AP (Apr. 16, 2014) The Buenos Aires Zoo debuted a trio of rare white Bengal tiger cubs on Wednesday. (April 16) 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