University of Pittsburgh’s Robert Bowser, PhD, and Ronald Hamilton, MD, were part of a joint research effort that identified a molecular signature common to both familial and sporadic cases of amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease. The finding reveals that a peptide found in a gene in spinal cord fluid is common to patients with the disease. The work was done through a collaboration of University at Buffalo (UB) chemists with scientists studying ALS at California Pacific Medical Center Research Institute, The Johns Hopkins University, University of California at San Diego, and Pitt.
Researchers at California Pacific (led by Vishwanath R Lingappa, PhD) found an unknown protein species in nanogram quantities (billionth of a gram) in spinal cord fluid samples from ALS patients. At such low quantities, Troy Wood, PhD, associate professor of chemistry in UB's College of Arts and Sciences, explained, the standard analytical chemistry technologies are of no use.
"Only nanotechnology is capable of identifying a species in these amounts," he said. "Because of the minute amounts of analyte that are present in some samples, nanospray technologies, in particular, which reveal what we call a peptide's mass 'fingerprint,' have emerged as one of the most important tools in the field of proteomics."
In the ALS research, the UB researchers used trypsin, an enzyme, to digest or break down the unknown analyte into small peptide pieces that constitute the "fingerprint," which, in turn, allows researchers to identify the species through mass spectrometry. Through a nanospray emitter, it was found that the unique, cross-linked species contained superoxide dismutase, a protein that had been previously linked to only the familial form of ALS. This peptide provides researchers with an important piece of information as to where to focus future research.
In addition to Bowser, Hamilton, Wood, and Lingappa, other co-authors on the paper are William L. Wood, UB; Evgenia Alpert, Don Cleveland, Arie Gruzman, Jian Liu, the lead author, Robert G. Miller, and M. Dharma Prasad of the California Pacific Medical Center Research Institute; and, Jeffrey D. Rothstein of The Johns Hopkins University.
Illustration: Superoxide dismutase. -- Wikipedia.
University at Buffalo News Release (09/04/07)
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Proceedings of the National Academy of Sciences (Abstract: PNAS | July 24, 2007 | vol. 104 | no. 30 | 12524-12529)