Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UNC researchers create new tool to unravel the mysteries of metastasis

10.03.2014

The lab of Klaus Hahn, Ph.D., developed a new technique to help scientists map the interactions between the proteins at the heart of many diseases

Researchers at the UNC School of Medicine have devised a new biochemical technique that will allow them and other scientists to delve much deeper than ever before into the specific cellular circuitry that keeps us healthy or causes disease.


This is Klaus Hahn, Ph.D., UNC School of Medicine.

Credit: UNC

The method – developed in the lab of Klaus Hahn, PhD, and described in the journal Nature Chemical Biology – helps researchers study how specific proteins called kinases interact to trigger a specific cellular behavior, such as how a cell moves. These kinase interactions are extraordinarily complex, and their interactions remain largely unknown. But researchers do know that kinases are crucial operators in disease.

"I dare you to find a disease in which kinases are not involved," said Hahn, senior author of the study and the Thurman Distinguished Professor of Pharmacology. "These kinase processes have been very difficult to fully understand, but we all know they're very important."

For years, scientists have been able to tweak a kinase to see what would happen – such as causing cell death or cell movement or cellular signaling. But these experiments can only scratch the surface when it comes to understanding the cascade of kinase interactions that lead to a cellular behavior. Nor have these experiments been able to show the timing of rapid events. That's important, Hahn said, because when a protein is activated has a lot to do with how the cell will respond. Drug developers haven't been able to take this into account, which is likely one reason why some drugs that target proteins don't work as well as scientists had hoped.

"Imagine you're an electrician looking at a circuit board, and all you can do is plug something in and watch all the circuits light up, but you have no idea how the board really works," Hahn said. "What you'd like to do is put a probe on one component, turn it on, and see what immediately happens to the circuit components next to that one component."

If you could do this with all the circuit components, then this would allow you to learn how the circuitry is built.

"We are now doing this in live cells and seeing what happens," said Hahn, a member of the UNC Lineberger Comprehensive Cancer Center. "Kinases are the circuit components. And we can now activate just one kinase and study how it interacts with just one other molecule in real time."

These kinase circuits are critical for cellular activities, such as metabolism, signaling, protein regulation, movement, enzyme secretion, and many others. All kinases have nuanced differences but all of them share one little part that researchers call a domain.

Hahn's team, led in the lab by postdoctoral fellow Andrei Karginov, PhD, studied the sarcoma kinase (Src) and figured out a way to use that part to attach an artificial protein to render Src inactive. That artificial protein had a binding site. When Karginov added a drug analog to the solution in which the cell lived, the drug analog bound to that site, causing the kinase to reactivate. Karginov could activate the kinase to see how the circuits lit up – how the cell responded at any given time during the cell's transition from a stationary cell to a moving, metastatic cell.

They could see the reaction in real time, so they knew that what they did caused the cell to react. Other methods struggle with this. Genetically manipulating a cell, for instance, takes too much time, Hahn said. Before you can see the results of the experiment, other proteins compensate for the kinase that was shut down.

Hahn's technique got around that problem, which allowed his lab to take their work one step further.

Karginov developed a two-component system. In this new system, adding the drug caused the activated kinase to interact only with molecules that contain a second engineered protein. Not only could Karginov turn on the kinase at an exact time; he could now tell the kinase exactly which circuit component to interact with.

They found that when Src was linked only to the kinase FAK, the cell's shape changed; it extended huge arms, or protrusions, but the cell didn't create new protrusions. When Src was linked with only the kinase CAS, the cell added new protrusions and the cell's adhesion ability improved. These are the behaviors that cancer cells need to move. In essence, Hahn's lab figured out a way to pinpoint precise mechanisms underlying metastasis.

"What this paper really does is show how all of this can be done to any kinase you want," Hahn said. "Our lab is interested in metastasis. But our hope is that our tool goes well beyond our narrow field of study. You just have to ask yourself, 'how important are kinases to disease?' And the answer is they're very important; they are everywhere."

###

Klaus Hahn, PhD, the senior author of the study, has a joint appointment with the UNC Eshelman School of Pharmacy. Karginov, the first author, is now an assistant professor of pharmacology at the University of Illinois-Chicago. Other authors include UNC research assistant professor Dennis Tsygankov and UNC professor of pharmacology Timothy Elston, PhD.

This research was funded through a grant from the National Institutes of Health.

Mark Derewicz | EurekAlert!
Further information:
http://www.unch.unc.edu

Further reports about: UNC circuit interact interactions kinases metastasis pharmacology proteins

More articles from Life Sciences:

nachricht A cell senses its own curves: New research from the MBL Whitman Center
29.04.2016 | Marine Biological Laboratory

nachricht A New Discovery in the Fight against Cancer: Tumor Cells Switch to a Different Mode
29.04.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Tiny microbots that can clean up water

Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.

Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...

Im Focus: ORNL researchers discover new state of water molecule

Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.

In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...

Im Focus: Bionic Lightweight Design researchers of the Alfred Wegener Institute at Hannover Messe 2016

Honeycomb structures as the basic building block for industrial applications presented using holo pyramid

Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...

Im Focus: New world record for fullerene-free polymer solar cells

Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences (CAS). This work is about avoiding costly and unstable fullerenes.

Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences...

Im Focus: Ultra-thin glass is up and coming

As one of the leading R&D partners in the development of surface technologies and organic electronics, the Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP will be exhibiting its recent achievements in vacuum coating of ultra-thin glass at SVC TechCon 2016 (Booth 846), taking place in Indianapolis / USA from May 9 – 13.

Fraunhofer FEP is an experienced partner for technological developments, known for testing the limits of new materials and for optimization of those materials...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The “AC21 International Forum 2016” is About to Begin

27.04.2016 | Event News

Soft switching combines efficiency and improved electro-magnetic compatibility

15.04.2016 | Event News

Grid-Supportive Buildings Give Boost to Renewable Energy Integration

12.04.2016 | Event News

 
Latest News

Winds a quarter the speed of light spotted leaving mysterious binary systems

29.04.2016 | Physics and Astronomy

Fiber optic biosensor-integrated microfluidic chip to detect glucose levels

29.04.2016 | Health and Medicine

A cell senses its own curves: New research from the MBL Whitman Center

29.04.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>