Science Current Events | Science News | Brightsurf.com
 
Email a Friend Send to a friend
Printer Friendly Print Hopkins researchers develop new tool to watch real-time chemical activity in cells

Hopkins researchers develop new tool to watch real-time chemical activity in cells

July 24, 2006

Study has implications for speeding new drug design

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.

Johns Hopkins Medical Institutions



Related Chemical Activity Current Events and Chemical Activity News Articles
Scientists visualize how bacteria talk to one another
Using imaging mass spectrometry, researchers at the University of California, San Diego have developed tools that will enable scientists to visualize how different cell populations of cells communicate.

Team led by Scripps Scientists increases understanding of two types of blindness
Though based on mouse studies, the research bolsters the idea that humans suffering from these and other eye conditions may be able to help preserve function by adding antioxidants to their diet, and explains why this would work. The team also devised a new cell-based gene therapy technique that could eventually offer another option for arresting vision loss from these diseases.

Computer-designed molecule to clean up fluorocarbons?
The chemical bond between carbon and fluorine is one of the strongest in nature, and has been both a blessing and a curse in the complex history of fluorocarbons. Now, in a powerful demonstration of the relatively new field of "computational chemistry".

New paradigm will help identify leads for drug discovery
A new screening approach can profile compounds in large chemical libraries more accurately and precisely than standard methods, speeding the production of data that can be used to probe biological activities and identify leads for drug discovery.
More Chemical Activity Current Events and Chemical Activity News Articles
Chemical Activities

Chemical Activities
by Christie L. Borgford (Author), Lee R. Summerlin (Author)

Offering the teacher's edition of the same chemical demonstrations as found in Chemical Activities: Student Edition, this book provides additional information about the activity, some useful teaching tips, and a complete instructions for preparing any solutions or gathering any materials.

Historic Theater Poster (S), Hypnotist directing group of people to do unusual activities: wo

Historic Theater Poster (S), Hypnotist directing group of people to do unusual activities: wo
by Olde Yankee Map and Photo Shoppe

This is a museum quality, reproduction print on premium paper with archival/UV resistant inks.

Date: c. .

Print Info: Created by The Donaldson Litho. Co. Newport K.Y. Title devised. Forms part of the McManus-Young Collection. No. 2982. Transferred from; LC Rare Book and Special Collections Division; 1956.

Topics: Hypnotism. Police. Musicians. Riding. Theatrical productions.

Publisher: Russell-Morgan Print.

HISTORY OF THE THEATER POSTERS

Originally used to attract the public to performances and performers, these posters illustrate the wide range of popular, live entertainment in America from the late nineteenth to the early twentieth century. The bulk of the posters are color lithographs and woodcuts and come from three main genres: Magic Posters, Minstrel Posters,...

Chemistry Basics Series: Complete Set (3 DVDs, Activity Masters and Teacher Guides)

Chemistry Basics Series: Complete Set (3 DVDs, Activity Masters and Teacher Guides)
Also With: MS Harvey D. Goodman (Producer)

by Harvey Goodman The focus of this DVD trilogy is to permit the student to learn through an interactive, experiential venue. Scientists conduct experiments that require students to observe, interpret and infer conclusions. Throughout the series inquiry based questions challenge students to discover the concept and apply the facts. The Three-DVD Chemistry Basics Series includes: (1) Matter; (2) Atomic Theory and The Periodic Table; and (3) Changes in Matter (Chemical Reactions). The DVDs in this series were first published in 2003. Great for children in Middle School. Running time is approximately 60 minutes total.

Nature Wonders NAMASKARD Iceland

Nature Wonders NAMASKARD Iceland
Directed By: TravelVideoStore.com
Also With: TravelVideoStore.com (Producer)



Intro CXL

Intro CXL
Chemical Activity (Primary Contributor)



Physical and Chemical Changes Activity Book

Physical and Chemical Changes Activity Book
by Kathleen Hilmes (Author)

This book presents a program of basic studies in physical and chemical changes of matter. The definition of matter is presented along with explanations of states and properties of matter. Topics include atoms, molecules, elements, compounds, mixtures, solutions, symbols, and formulas. Each of the twelve teaching units in this book is introduced by a color transparency, which emphasizes the basic concept of the unit and presents questions for discussion. Reproducible student pages provide reinforcement and follow-up activities. The teaching guide offers descriptions of the basic concepts to be presented, background information, suggestions for enrichment activities, and a complete answer key. 32 pages, for grades 5-9.

Kickbutt Amped Energy Ballz Cherry Kick, 56-Count Box

Kickbutt Amped Energy Ballz Cherry Kick, 56-Count Box
by Energy Ballz

Kickbutt amped energy ballz are a true functional food for instant and sustained energy, providing hours of alertness and vigor. Kickbutt amped energy ballz are formulated with the ideal blend of ingredients. They contain high quality whey protein isolates, complex carbohydrates, energizer vitamins and herbs and caffeine. Kickbutt amped energy ballz are low in fat, trans-fat-free, peanut free, and only 38 calories per ball.

Micro Chem XM5000

Micro Chem XM5000
by Smithsonian Science Activities

This super safe chemistry set includes over 1500 experiments and procedures!It includes 20 microchemical vials, safety goggles, test tubes, measuring cups, galvanometer, laboratory balance, pipettes, microplate, and is contained in a standing storage chest. Perform over 1500 experiments in the gaseous phases of matter, chemical models, solutions, acid and bases, electro-chemistry, organic chemistry and much more. The revolutionary concept uses the latest in MicroChemistry Technology, and the experiments are approved by the Smithsonian Institution Scientists. Warning: To be used solely under the supervision of adults. Contains some chemicals which can be harmful if misused. Keep out of the reach of small children.

Kickbutt Amped Energy Ballz Cappuccino Kick, 28 (2-ball) Count Box

Kickbutt Amped Energy Ballz Cappuccino Kick, 28 (2-ball) Count Box
by Energy Ballz

Kickbutt amped energy ballz are a true functional food for instant and sustained energy, providing hours of alertness and vigor. Kickbutt amped energy ballz are formulated with the ideal blend of ingredients. They contain high quality whey protein isolates, complex carbohydrates, energizer vitamins and herbs and caffeine. Kickbutt amped energy ballz are low in fat, trans-fat-free, peanut free, and only 38 calories per ball.

Fungicidal Activity: Chemical and Biological Approaches to Plant Protection (Wiley Series in Agrochemicals & Plant Protection)

Fungicidal Activity: Chemical and Biological Approaches to Plant Protection (Wiley Series in Agrochemicals & Plant Protection)
by David Hutson (Editor), Junshi Miyamoto (Editor)

Increasing resistance to established fungicides has stimulated the search for novel fungicides with new modes of action. Environmental concerns now also demand that these have low environmental impact and toxicity. Fungicidal Activity discusses new approaches to fungicide development including biological control and genetic engineering, and takes a global view of the future of fungicidal development. Fungicidal Activity is a volume in the Wiley Series in Agrochemicals and Plant Protection. This series brings together current scientific and regulatory knowledge and perspectives on all aspects of the use of chemicals and biotechnology in agriculture.

© 2009 BrightSurf.com