Proteins are essential building blocks of biology, used in muscle, brain, blood and hormones. If the genes are the blueprints, the proteins patterned on them are the hammers and tongs of life.
Proteins are not only numerous — humans have more than a 100,000 varieties — but each one has a complex structure that determines its exact function in the biological realm. Just as tissue from cats and kangaroos can be distinguished by studying the individual "letters" of their genetic codes, protein A can be distinguished from protein B by looking at the amino-acid subunits that compose all proteins.
The fastest way to count and identify proteins is to use a mass spectrometer, a precise instrument that measures chemical compounds by mass. "Mass spec is an essential part of modern biology, and most people use it to look at variations in proteins," says Joshua Coon, a professor of chemistry and biomolecular chemistry.
Because mass spectrometers are expensive, and proteins are both numerous and ubiquitous, chemists have recently learned to double up their samples so they can, for example, compare normal tissue to diseased tissue in a single run.
Knowing how the proteins change when good tissue goes bad suggests what has gone wrong.
Now, Coon has doubled-down on the doubling-up process with a technique that has the potential to run as many as 20 samples at once. The new process, described in the journal Nature Methods, has already gone to work, says Alexander Hebert, a graduate student who was first author on the new publication.
"Working with John Denu at the Wisconsin Institute for Discovery, we are looking at mice that lived with or without caloric restriction," says Hebert. Caloric restriction is known to increase lifespan in many animals, and scientists are eager to unravel the biochemical pathways that explain this life extension. "Some of these mice have lost a certain gene related to metabolism, so we are comparing four types of tissue all at once. We can look at the brain, liver or heart, and ask, how does the abundance of proteins vary?"
Already, Coon and Hebert have performed six simultaneous analyses using the new technique; but it could actually do batches of 20, Coon says.
Key to the original doubling-up process was inserting a "tag" into the amino acids that gives the proteins a slightly different mass. The tags are isotopes — chemically identical atoms that have different masses.
To prepare two samples, one would receive an amino acid containing common isotopes, and the other special, heavier isotopes. The result — proteins that are chemically identical but have different masses — can easily be identified in a mass spectrometer.
The new journal report by Coon and Hebert describes a way to use amino acids built from a broader range of isotopes that would be expected to have identical mass, but do not because some of their mass has been converted to energy to hold the atomic nuclei together. Without this energy, the positively charged proteins would repel each other and the atomic nucleus would be destroyed. The tiny loss of mass due to this conversion to binding energy can be detected in the new, ultra-precise mass spectrometers that are now installed in several labs on campus.
The mass difference in the new technique is more than 1,000 times below the mass differences in the existing doubled-up technique, but it is enough to count and identify proteins from six — and, theoretically, 20 — samples at once. The researchers applied for a patent last fall and assigned the rights to the Wisconsin Alumni Research Foundation.
The study of proteins is the forefront of biology, says Coon, and so it's easy to envision uses for a faster, cheaper analytical tool. "We could look for protein differences in cells from 100 different tumors. The proteins might reveal that you are dealing with five or 10 distinct syndromes in this seemingly-identical cancer, which could suggest treatments that are more tailored to the individual. If you compare proteins in normal versus tumor tissue, you might find a certain protein at uncommonly high concentrations, or [that] was modified in certain ways. You might identify a protein that would help diagnose this cancer sooner. Or — and this is the real pay dirt — you might identify a protein that is so vital to the cancer that it would make an ideal target for a new drug."
— David Tenenbaum, 608-265-8549, email@example.com
Joshua Coon | Source: EurekAlert!
Further information: www.wisc.edu
More articles from Life Sciences:
Estrogen: Not just produced by the ovaries
05.12.2013 | University of Wisconsin-Madison
Iranian biodiversity was underestimated, several new candidate species found
05.12.2013 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere
The Light: Global study gets underway with online user survey
Light has a fundamental impact on our sense of well-being and performance. In cooperation with Zumtobel, a supplier of lighting solutions, Fraunhofer IAO has launched a global user survey of lighting quality in offices. The objective is to identify the best lighting conditions for a variety of spaces and lighting ...
Quantum entanglement, a perplexing phenomenon of quantum mechanics that Albert Einstein once referred to as “spooky action at a distance,” could be even spookier than Einstein perceived.
Physicists at the University of Washington and Stony Brook University in New York believe the phenomenon might be intrinsically linked with wormholes, hypothetical features of space-time that in popular science fiction can provide a much-faster-than-light shortcut from one part of the universe to another.
But here’s the catch: One couldn’t actually ...
A star is formed when a large cloud of gas and dust condenses and eventually becomes so dense that it collapses into a ball of gas, where the pressure heats the matter, creating a glowing gas ball – a star is born.
New research from the Niels Bohr Institute, among others, shows that a young, newly formed star in the Milky Way had such an explosive growth, that it was initially about 100 times brighter than it is now. The results are published in the scientific journal, Astrophysical Journal Letters.
The young ...
EPFL scientists have shown how to achieve a dramatic increase in the capacity of optical fibers; Their simple, innovative solution reduces the amount of space required between the pulses of light that transport data
Optical fibers carry data in the form of pulses of light over distances of thousands of miles at amazing speeds. They are one of the glories of modern telecommunications technology.
However, their capacity is limited, because the pulses of light need to be lined up one after the other in ...
NASA's Hurricane and Severe Storms Sentinel airborne mission known as HS3 wrapped up for the 2013 Atlantic Ocean hurricane season at the end of September, and had several highlights. HS3 will return to NASA’s Wallops Flight Facility in Wallops Island, Va., for the 2014 Atlantic hurricane season.
During the 2013 mission, two unmanned Global Hawks flew from Wallops for the first time. The mission highlights included studying the Saharan Air Layer, following the genesis of a tropical storm, finding a unique hybrid core or center circulation in a redeveloped storm, obtaining measurements on the strongest side of ...
05.12.2013 | Health and Medicine
05.12.2013 | Ecology, The Environment and Conservation
05.12.2013 | Information Technology
05.12.2013 | Event News
04.12.2013 | Event News
12.11.2013 | Event News