Dr. Michael Giddings
Macs and the Next Frontier: Proteomics
Now that scientists have decoded the human genome, they’re taking the next and much more challenging step in understanding the molecular foundations of life. The new science of proteomics catalogs and analyzes each protein that a gene produces. Far more varied and complex than DNA, proteins carry out every chemical reaction essential to life. They are the beams and rafters of cells, the hormones, enzymes, circuits and even the glue that binds the body together.
One of the scientists who pursues proteomics — with the help of Macs and a cluster of Xserve servers — is biologist Dr. Michael Giddings at the University of North Carolina.
Mapping Proteins
“From a biologist’s perspective,” says Dr. Giddings, assistant professor of microbiology and immunology at the university, “proteomics is an important technology, but we’re interested in applying it to a specific problem. The genomes of microbes are very adaptable organisms; they change very rapidly. That’s one of the reasons there are such problems with antibiotic resistance and new diseases breaking out.”
“The genomes of microbes are very adaptable organisms; they change very rapidly.”
— Dr. David Fresco, assistant professor of psychology, Kent State University
“We want to use proteomics technology to try to get better insight into how these microbes are changing with time. If we could understand how these microbes react, we could develop a new antibiotic that targets changes, preemptively.”
Combining mass spectrometry with analysis on Macs, Dr. Giddings and his team are working to identify which genes produce which proteins, measuring the shape of each protein — what a protein does is largely determined by its shape — and identifying its chemical composition.
“Mass spectrometry,” says Dr. Giddings, “can perform very precise mass measurements on both proteins and the products of proteins, which are called peptides. But all you’re doing is measuring masses. We need to understand what those measurements mean.” To find out, Dr. Giddings uses Macs.
Bypassing Databases
After using a mass spectrometer to measure the mass and describe a protein that has been expressed in a cell, Dr. Giddings runs a UNIX software program he wrote for the Mac to link the “fingerprint” of the protein back to the genome. “A number of programs are out there to do it,” says Dr. Giddings, “but they need a database of known genes and sometimes those databases are pretty limited. If the gene that encodes a protein isn’t present in the database, we’re going to miss it.”
“Our program is unique,” Dr. Giddings explains, “in that it bypasses those databases and matches proteins against the raw genome sequence. We take that genome sequence — three billion characters long for the human genome, much shorter for microbes — and calculate all the possible peptides that this genome sequence could produce. Then, each time we do the mass spectrometry, we can go in and map out places where a cluster of peptides match up in a small region of the genome.”
“That’s important, because there’s enough noise in the mass spectrometry and processes that we never get just a single peptide matching on the whole genome. We get matches all over the place for different measurements. The key is finding the one place where enough of those add up to make the unique place that expresses that particular protein, as opposed to random coincidence.”
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