When a group of renowned analytical chemists and bioinformaticists founded systems biology startup Beyond Genomics last March, it was clear proteomics would play a role in the companys vision to integrate genetic, protein, and metabolite data into a computational model of how mammalian organisms function.
The Waltham, Mass.-based company may not yet have refined its bioinformatics strategy for bridging these separate forms of data into a seamless whole, but in recent weeks at least the proteomics platform is beginning to fall into place.
Earlier this month, Beyond Genomics announced that it had licensed mass spectrometry technology from Indiana University called ion mobility mass spectrometry (IMMS), and last week the companys chief technology officer told ProteoMonitor that the company would combine stable isotope tagging with IMMS and other mass spectrometry techniques in a liquid chromatography-based approach to studying the differential expression of proteins in diseased and normal cells.
The general concept of differential protein expression is certainly not new to proteomics, but Beyond Genomics is the first company to apply the IMMS technique in this capacity. Although IMMS was originally developed to study inorganic molecules, David Clemmer, an analytical chemist at Indiana University and a co-founder of the company, began applying the technique in his academic laboratory several years ago to determine the structure of biological molecules.
The technique is useful in proteomics because it allows the spectrometer to apply an extra dimension in which to separate proteins, said Steve Naylor, Beyond Genomics CTO, who joined the company earlier this fall. When peptides are sprayed into the instrument from the liquid chromatograph, they pass through a drift tube filled with an inert gas. An applied voltage draws the peptides through the chamber, but the gas interferes with the motion of larger species, in effect separating the peptide fragments by size, even if they have the same molecular weight.
From the drift tube, peptide fragments then pass into a second chamber for time-of-flight mass spectrometry analysis, which separates peptides on the basis of mass-to-charge ratio. Naylor said the company is also planning to add a collision cell to the instrument, to allow the companys researchers to perform peptide sequencing using the IMMS spectrometer.
Clemmers instrument is going to give us a dimension of resolving capability that is anywhere from a hundred to a thousand times better than just doing conventional online chromatography, Naylor said. Its in effect a second generation proteomic analyzer.
IMMS + GIST = ?
Clemmer isnt the only member of Beyond Genomics advisory board to have contributed in some way to the companys intellectual property. Fred Regnier, a co-founder and chemist at Purdue University, has developed a method for labeling peptide fragments that Naylor intends to use to determine whether the peptides were derived from a diseased or normal sample.
The technique, called global internal standard technology (GIST), will allow Beyond Genomics researchers to label the N-terminus of the peptides and any free lysine side chains with a deuterated marker, Naylor said. Other companies involved in differential proteomics, such as GeneProt and Celera, are applying an analogous technique for labeling peptides, called ICAT, initially developed at the University of Washington.
Another member of the Beyond Genomics advisory board from Purdue University, Scott McLuckey, is contributing his research on applying software algorithms to the analysis of undigested proteins using ion trap mass spectrometry, Naylor said. The technique can analyze complex undigested protein mixtures by altering the electronics of the ion trap, he said.
In addition, the company is attempting to license functional proteomics technology from Naylors former academic institution, the Mayo Clinic in Rochester, Minn., where Naylor served as director of biomedical mass spectrometry and functional proteomics. At Mayo, Naylor led the development of methods for studying whether proteins from a cell lysate interact with specific proteins expressed in individual wells using a combination of protein microarray and mass spectrometry technology.
While Naylor and his team put the finishing touches on Beyond Genomics proteomics platform, the company as a whole continues to mold how it will put systems biology to work for its current and future pharmaceutical partners. In June, Beyond Genomics hired Eric Neumann, a former vice president at bioinformatics consulting firm 3rd Millennium, to direct the development of its bioinformatics platform. Naylor said the company has implemented its strategy for integrating its bioinformatics platform with proteomics, but Beyond Genomics capabilities in globally modeling cellular systems are still under development.
Beyond Genomics is currently working with Elan Pharmaceuticals to identify biomarkers for Alzheimers disease, and is in late-stage discussions with another unnamed partner, Naylor added.