Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Team's model aids understanding of protein networks --Work could impact cancer research

27.06.2007
An international team of researchers, including several from MIT, has developed a computational model that helps identify relationships between proteins and the enzymes that regulate them.

The work could help researchers understand the complex protein networks that influence human disease, including cancer. The researchers report their findings in the cover story of the June 29 issue of Cell.

The new method, known as NetworKIN, can trawl through existing research data and use it to illuminate protein networks that control cellular processes. It focuses on enzymes called kinases, which are involved in many cell signaling pathways, including repair of DNA damage that can lead to cancer.

The model was developed by researchers from MIT, the Samuel Lunenfeld Research Institute of Mount Sinai Hospital in Canada and the European Molecular Biology Laboratory in Germany.

... more about:
»Kinase »Yaffe »cellular process »developed »pathway

NetworKIN “gives us the tools to take the information we already have and begin to build a map of the kinase signaling pathways within the cells,” said Michael Yaffe, MIT associate professor of biology and biological engineering, a member of MIT's Center for Cancer Research (CCR) and one of the authors of the paper.

“By getting a network-wide view, multiple aberrant genes of kinase- controlled processes are more easily targeted,” said Rune Linding, a postdoctoral fellow with joint appointments through the CCR and Mount Sinai. “In the future, complex human diseases will be treated by targeting multiple genes.”

Kinases act by phosphorylating, or adding a phosphate group, to a protein. That signal tells a protein what it should be doing. Yaffe estimated that at any one time, 30 to 50 percent of the proteins in a cell are phosphorylated.

Because kinases play such a critical role in cellular processes, including DNA repair and cell division, scientists have been working to identify where phosphorylation takes place in a target protein.

Mass spectrometry makes it easy to identify those sites, but until now there has been no good way to figure out which kinases are acting on each site, Yaffe said.

“It's a huge bottleneck,” he said. “We're getting thousands of phosphorylation sites, but we don't know which kinase phosphorylated them, so we don't know what pathway to put them in.”

To solve that problem, the researchers developed a two-step approach.

In the first step, they used a pair of previously developed computer programs that can analyze the amino acid sequence of the phosphorylation site and predict which family of kinases is most likely to bind to and phosphorylate it.

However, each family includes several kinases, and the sequence alone cannot tell you which one acts on the site.

To pinpoint the kinases more accurately, the researchers developed a computational model that analyzes databases that contain information about signaling pathways and protein interactions. The program also performs “text mining” of published articles and abstracts to search for reported protein-kinase interactions.

By combining these two sources of information-sequences of the target proteins and contextual information about the interaction between proteins and kinases-the computational model can develop a detailed network that would be very difficult to create by manually examining the available data.

“The sequence gets us into the ballpark, but it's all of this contextual information that helps us figure out specifically which kinases are acting on which sites,” said Yaffe, who is also affiliated with the Broad Institute of MIT and Harvard, and Beth Israel Deaconess Medical Center.

Other MIT authors on the paper are Gerald Ostheimer, a postdoctoral fellow in biological engineering, Marcel van Vugt, a postdoctoral fellow at the Center for Cancer Research, and Leona Samson, director of the Center for Environmental Health Sciences and professor of biology and biological engineering.

The research was funded by the European Commission FP6 Programme, the Danish Research Council for the Natural Sciences, the Lundbeck Foundation, Genome Canada and the National Institutes of Health Integrative Cancer Biology Program.

Written by Anne Trafton, MIT News Office

Elizabeth A. Thomson | MIT News Office
Further information:
http://www.mit.edu

Further reports about: Kinase Yaffe cellular process developed pathway

More articles from Life Sciences:

nachricht More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>