Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Uncharted Territory: Scientists Sequence the First Carbohydrate Biopolymer

11.10.2011
DNA and protein sequencing have forever transformed science, medicine, and society. Understanding the structure of these complex biomolecules has revolutionized drug development, medical diagnostics, forensic science, and our understanding of evolution and development. But, one major molecule in the biological triumvirate has remained largely uncharted: carbohydrate biopolymers.

Today, for the first time ever, a team of researchers led by Robert Linhardt of Rensselaer Polytechnic Institute has announced in the October 9 Advanced Online Publication edition of the journal Nature Chemical Biology the sequence of a complete complex carbohydrate biopolymer. The surprising discovery provides the scientific and medical communities with an important and fundamental new view of these vital biomolecules, which play a role in everything from cell structure and development to disease pathology and blood clotting.


Rensselaer Polytechnic Institute
Structure of the bikunin. The portion on the left corresponds to the sugar part of the molecule, the sequence of which was determined in the current study. The portion on the right corresponds to the protein part of bikunin.
Nature Chemical Biology

The paper is titled “The proteoglycan bikunin has a defined sequence.”

“Carbohydrate biopolymers, known as glycosaminoglycans, appear to be really important in how cells interact in higher organisms and could explain evolutionary differences and how development is driven. We also know that carbohydrate chains respond to disease, injury, and changes in the environment,” said Linhardt, who is the Ann and John H. Broadbent Jr. ’59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer. “In order to understand how and why this all happens, we first need to know their structure. And today, at least for the simplest glycosaminoglycan structure, we can now do this.”

The first glycosaminoglycan sequenced was obtained from bikunin. Bikunin is a proteoglycan, a protein to which a single glycosaminoglycan chain is attached. Unlike less sophisticated carbohydrate biopolymers, such as starch and cellulose, the proteoglycans are decorated with structurally complex carbohydrates that enable them to perform more sophisticated and defined roles in the body. Bikunin, for example, is a natural anti-inflammatory that is used as a drug for the treatment of acute pancreatitis in Japan. It has the simplest chemical structure of any proteoglycan. Linhardt views the discovery of the structure of bikuin as the first step on the ladder to the discovery of the structure of more complex proteoglycans.

“The first genome sequences of DNA were on the simplest organisms such as bacteria. Once the technology was developed it ultimately led to the sequencing of the human genome,” he said. “In our efforts to sequence carbohydrate biopolymers we don’t yet know if the defined structure we observe for this simple protoglycan will hold for much more complex proteoglycans.”

But, looking for structure in more complex proteoglycans will be among the next steps in the research for Linhardt and his team. The search for structure could help put to rest a long-running debate in the scientific community as to whether complex carbohydrate biopolymers require a defined structure to function.

“Despite all that is known about glycan formation, our understanding has not yet been deep enough to infer sequence or even determine if sequence occurs,” Linhardt said. “These findings represent a new way of looking at these complex biomolecules as ordered structures.”

Linhardt’s research into carbohydrate sequencing began 30 years ago. In his previous work, he determined that some order existed in at least a portion of some carbohydrate biopolymers, but it did not represent the entire finished puzzle.

“Previously, we could see a pattern, but we could not see if all the chains were playing the same music. The tools did not yet exist. Now we can recognize it as a symphony.”

To uncover the entire structure, Linhardt and his team, which was led by his doctoral student Mellisa Ly, borrowed a technique from the field of protein research called the proteomics top-down approach. As opposed to the bottom-up approach that first breaks apart a complex biopolymer into pieces and then rebuilds it piece by piece like a jigsaw puzzle, the top-down approach used by Linhardt and colleagues allows the researcher to picture the whole intact puzzle. This can only be accomplished with some of the most sophisticated technology available to the scientific community today, including very high-powered mass spectrometers.

Linhardt used a mass spectrometer located in the Rensselaer Center for Biotechnology and Interdisciplinary Studies (CBIS) to make his initial discoveries, and had these results independently confirmed on a separate and higher-level spectrometer at the University of Georgia. Mass spectrometers break down a molecule into separate charged particles or ions. These ions can then be categorized and analyzed based on their mass-to-charge ratio. These ratios then allow for sequencing of the entire molecule.

“This was truly the convergence of really sophisticated spectroscopy and its application to biology,” Linhardt said. “We were fortunate to have a lot of time to play with the instrument at CBIS to understand its capabilities.”

Beyond the technology it also took faith and determination. According to Linhardt, “It takes a student that is willing to try something even when the odds are pretty low. If it doesn’t work, you make incremental progress. If it does work, you can make a great discovery. But, from the beginning you need to be a believer that it is worth taking the chance because it takes a lot of hard work in the lab.”

And the odds weren’t in Linhardt’s favor. Despite being the most simple of proteoglycans, there were still 290 billion different possible sequences for the molecule.

“The first sample we looked at, we got the structure,” Linhardt said. “In the end we did 15 chains and they all came back playing the same exact symphony.”

The research is funded by the National Institutes of Health.

Linhardt and Ly were joined in the research by Tatiana Laremore of Rensselaer; Franklin Leach and Jonathan Amster of the University of Georgia; and Toshihiko Toida of Chiba University in Japan.

Gabrielle DeMarco | Newswise Science News
Further information:
http://www.rpi.edu

Further reports about: Bikunin Biopolymer CBIS Carbohydrate DNA genome sequence mass spectrometer territory

More articles from Life Sciences:

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>