Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

International consortium builds 'Google Map' of human metabolism

04.03.2013
Building on earlier pioneering work by researchers at the University of California, San Diego, an international consortium of university researchers has produced the most comprehensive virtual reconstruction of human metabolism to date.

Scientists could use the model, known as Recon 2, to identify causes of and new treatments for diseases like cancer, diabetes and even psychiatric and neurodegenerative disorders. Each person's metabolism, which represents the conversion of food sources into energy and the assembly of molecules, is determined by genetics, environment and nutrition.

The researchers presented Recon 2 in a paper published online March 3 in the journal Nature Biotechnology.

Doctors have long recognized the importance of metabolic imbalances as an underlying cause of disease, but scientists have been ramping up their research on the connection as a result of compelling evidence enabled by the Human Genome Project and advances in systems biology, which leverages the power of high-powered computing to build vast interactive databases of biological information.

"Recon 2 allows biomedical researchers to study the human metabolic network with more precision than was ever previously possible. This is essential to understanding where and how specific metabolic pathways go off track to create disease," said Bernhard Palsson, Galletti Professor of Bioengineering at UC San Diego Jacobs School of Engineering.

"It's like having the coordinates of all the cars in town, but no street map. Without this tool, we don't know why people are moving the way they are," said Palsson.

He likened Recon 2 to Google mapping for its ability to merge complex details into a single, interactive map. For example, researchers looking at how metabolism sets the stage for cancerous tumor growth could zoom in on the "map" for finely detailed images of individual metabolic reactions or zoom out to look at patterns and relationships among pathways or different sectors of metabolism. This is not unlike how you can get a street view of a single house or zoom out to see how the house fits into the whole neighborhood, city, state, country and globe. And just as Google maps brings together a broad set of data – such as images, addresses, streets and traffic flow – into an easily navigated tool, Recon 2 pulls together a vast compendium of data from published literature and existing models of metabolic processes.

As a multi-scale representation of the human metabolic network, Recon 2 provides essential context for data being reviewed by researchers. Palsson and other scientists in the field have already successfully demonstrated the utility of such models in simple organisms such as yeast and E.coli. As a result, they have been able to engineer these organisms in the lab to improve the efficiency of ethanol production and predict drug resistance in bacteria.

One of the most promising applications for the network reconstruction is the ability to identify specific gene expressions and their metabolic pathways for targeted drug delivery. Large gene expression databases are available for human cells that have been treated with molecules extracted from existing drugs as well as drugs that are in development. Recon 2 allows researchers to use this existing gene expression data and knowledge of the entire metabolic network to figure how certain drugs would affect specific metabolic pathways found to create the conditions for cancerous cell growth, for example. They could then conduct virtual experiments to see whether the drug can fix the metabolic imbalance causing the disease.

Palsson's Systems Biology Research Group at UC San Diego built the first virtual reconstruction of the human metabolism network, known as Recon 1, in 2007 with a six-person team. It featured more than 3,300 known biochemical reactions documented in over 50 years of metabolic research. Recon 2, which contains more than 7,400 reactions, was built by bringing together researchers from dozens of institutions around the globe in a series of "jamboree" meetings to refine and consolidate the data used in the reconstruction. Palsson said this jamboree approach helped the group establish common standards to build a consensus reconstruction, simplify its usability for biomedical researchers, and increase its transparency. Recon 2 will facilitate many future biomedical studies and is freely available at http://humanmetabolism.org.

Recon 2 is already proving its utility, according to Ines Thiele, a professor at the University of Iceland and UC San Diego alumna, who led the Recon 2 effort. Thiele earned her Ph.D. in bioinformatics as a student of Palsson's and was part of the original Recon 1 team. Several other UC San Diego alumni, and former Palsson students, participated in the consortium from their new institutions, including Neema Jamshidi (Ph.D., 2008, M.D., 2009), who is now interning at UCLA; Jason Papin (Ph.D., 2004), a professor at the University of Virginia; and Nathan Price (Ph.D., 2005), who is a professor at the Institute for Systems Biology in Seattle, Wash.

Thiele said Recon 2 has successfully predicted alterations in metabolism that are currently used to diagnose certain inherited metabolic diseases.

"The use of this foundational resource will undoubtedly lead to a myriad of exciting predictions that will accelerate the translation of basic experimental results into clinical applications," said Thiele. "Ultimately, I envision it being used to personalize diagnosis and treatment to meet the needs of individual patients. In the future, this capability could enable doctors to develop virtual models of their patients' individual metabolic networks and identify the most efficacious treatment for various diseases including diabetes, cancer and neurodegenerative diseases."

As much as Recon 2 marks a significant improvement over Recon 1, there is still much work to be done, according to the research team. Thiele said Recon 2 accounts for almost 1,800 genes of an estimated 20,000 protein-coding genes in the human genome. "Clearly, further community effort will be required to capture chemical interactions with and between the rest of the genome," she said.

The international consortium includes researchers from the following institutions: University of Vienna, Austria; Charité– Universitätsmedizin Berlin, Germany; Jacobs University Bremen, Germany; Center for Systems Biology, University of Iceland; Okinawa Institute Science and Technology, Japan; Luxembourg Centre for Systems Biomedicine; University of Amsterdam, the Netherlands; Netherlands Bioinformatics Centre, the Netherlands; Vrije Universiteit, Amsterdam, the Netherlands; Netherlands Consortium for Systems Biology; Institute of Cell Biophysics, Moscow region, Pushchino, Russia; Chalmers University of Technology, Sweden; University of Manchester, United Kingdom; Manchester Institute of Biotechnology, UK; Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, UK; European Bioinformatics Institute, UK; Babraham Institute, Cambridge, UK; University of Warwick, UK; University of Edinburgh, UK; University of Sheffield, UK; University of California, San Diego; University of Virginia; Virginia Tech; Centre for Advanced Discovery and Experimental Therapeutics (CADET), University of North Texas; Genome Designs, Inc., Walnut Creek, Calif.; California Institute of Technology; and Institute for Systems Biology, Seattle, Wash.

Catherine Hockmuth | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>