Nuno Bandeira, a computer science and engineering Ph.D. candidate at UC San Diego's Jacobs School of Engineering has won the 2006 Human Proteome Organization's Young Investigator Award for work on snake venom proteins. The award-winning protein analysis technique is expected to aid drug development efforts, help scientists better understand cancer proteins and, perhaps, let scientists dive into dinosaur genetics.
Modified snake venom proteins have been used in the past to create blood thickening and thinning drugs and powerful pain killers -- but there is much more to learn about proteins from snake venom – and Bandeira's research provides a new and improved way to study them. In fact, the technique should be useful in studying a wide range of highly modified proteins that researchers have had trouble studying in the past, due to technical limitations.
The award-winning protein analysis technique gives scientists two new technical capabilities: the ability to glean amino acid sequences from mixtures of unidentified proteins and identify the specific ways in which proteins have been modified. Bandeira and colleagues present their improved protein sequencing technique with an analysis of venom proteins from western diamondback rattlesnakes.
Nuno Bandeira performed this research with his Ph.D. advisor -- UCSD computer science and engineering professor Pavel Pevzner, and Karl Clauser from the Broad Institute of MIT and Harvard. Pevzner is also the director of the newly-established Center for Algorithmic and Systems Biology (CASB) at the UCSD Division of Calit2.
In the language of biology, the new technique can be described as "shotgun protein sequencing of post-translationally modified proteins."
"Shotgun" refers to the process of "blowing" the proteins to small pieces. After several interim steps, scientists then put the pieces back together and reconstruct the original proteins, using the weights of amino acids as one of the guides.
The second half of the technique description -- "Post-translationally modified proteins" – refers to proteins that have been altered after being translated from the original genome "recipe." Post-translational modifications are very common and regularly change the way proteins work.
In 2004, Pevzner, Bandeira and others pioneered the use of this shotgun technique for generating amino acid sequences for unmodified proteins. The new work extends the shotgun approach to the kinds of highly modified mixes of proteins found in snake venom as well as proteins produced by some cancers.
"We had already figured out how to use the shotgun approach to get amino acid sequences from single purified proteins, but purified proteins are really hard to get. Working with purified proteins makes the computational part simpler but the experimental part harder," said Bandeira.
The new shotgun approach also surpasses current protein identification techniques which require researchers to guess what set of proteins and what set of modifications they are looking for. "We remove that guesswork. Give us the data and we will tell you the amino acid sequences and the modifications of the proteins in the sample," said Bandeira. In addition, the new protein sequencing technique is completely automated and can be used to process samples that the older, labor-intensive "Edman degradation" procedure could not.
Bandeira and the other finalists for the young investigator award were judged on their submitted abstracts, their presentations at the Human Proteome Organization's Fifth Annual World Congress on Monday October 30, 2006 in Long Beach, Calif., as well as letters of recommendation and resumes.
"Nuno was the only Ph.D. student among the five finalists. He won this award in competition with star faculty members," said Dr. Pevzner.
A longer description of the findings has been submitted for publication.
Because scientists have not fully sequenced any snake genomes, getting amino acid sequences for individual snake venom proteins is especially relevant. Genome sequences, however, don't tell the entire story of genetic variation, explained Bandeira.
"We have diseases like cancer that are not a single disease but a universe of diseases created by different rearrangements in the genome that may yield new proteins. We're looking at ovarian cancer proteins right now," said Bandeira.
Single nucleotide polymorphisms or (SNPs) – single nucleotide substitutions – and genes that vary in the way their segments are sequenced provide two additional examples of genetic variability that may be picked up by protein sequencing but missed by some genome sequencing approaches.
While the improved protein sequencing technique is expected to advance science and medicine in the long term, the award itself may be useful in the short term.
"This award will definitely help in applying for jobs," said Bandeira, who will finish his Ph.D. in spring 2007.
"The award has given our bioinformatics group nice visibility. It will be easier to start up collaborations with groups of biologists who are generating really good data," said Bandeira. He and Pevzner are organizing Algorithmic Biology 2006 on Thursday, November 30, 2006 -- a conference at the UCSD Division of Calit2 that will bring computational and experimental researchers together to discuss some of the common challenges facing biologists working in today's post-genomic age.
Algorithmic Biology 2006 is the first in a series of conferences to be organized by the newly-established Center for Algorithmic and Systems Biology (CASB) at Calit2 in La Jolla. The new center brings together algorithmic and systems biology researchers and students from UCSD, Burnham Institute, and The Scripps Research Institute. The conference will be followed by the RECOMB satellite conferences on Systems Biology December 1-2, 2006 (Chair: Trey Ideker, UCSD) and Computational Proteomics on December 2-3, 2006 (Chair: Vineet Bafna, UCSD), which Bandeira is also helping to organize.
"It's going to be a really excellent four days at UCSD. The list of invited speakers is impressive. For those four days, all bioinformatics around here should stop. People should come, listen and ask tough questions. If you are going to ask the tough questions, these are the people you should be asking," said Bandeira.