March 2010

Systems Biology for Biochemists Merging the Experimental and Theoretical


Valérie de Crécy-Lagard

In October 2009, approximately 60 scientists met for the first “Systems Biology for Biochemists” American Society for Biochemistry and Molecular Biology Special Symposium at Granlibakken resort in Lake Tahoe, Calif. As biology is now fully in the post-genomic era, the question of how the availability of more than a thousand genome sequences changes the way biochemists design and conduct their experiments is a pressing one.

Arcady Mushegian of Stowers Institute for Medical Research organized the meeting to allow experimental and theoretical scientists to come together and see how biochemistry is now integrated at several levels with many other fields. This integration was apparent during the first evening, when Gregory A. Petsko of Brandeis University presented his work that combined yeast genetics and three-dimensional structures to rapidly identify drug targets and drug candidates in Parkinson’s disease. Another “big picture” presentation was given by Eugene V. Koonin of the National Center for Biotechnology Information, who showed that evolutionary principles can be extracted from whole genome sequences as evolutionary biology goes from “stamp collecting to physics.”

Alexandre V. Morozov

The emphasis of the next day’s session was on reconstructing ancestral and minimal biochemical pathways. In the morning, Vadim Gladyshev of Harvard Medical School and Valérie de Crécy-Lagard of the University of Florida emphasized the power of using comparative genomic approaches to discover new pathways and physiological trends. Gladyshev presented an impressive analysis of players in metal trace-element metabolism in 700 genomes (1). De Crécy-Lagard showed that in silico data-mining approaches can be used to identify many missing tRNA modification genes. The field of synthetic biology was represented by Mikkel Algire of the J. Craig Venter Institute. He described a general method that eliminates ligation steps in gene, operon or plasmid assembly that was used to assemble a whole Mycoplasma mycoides genome in yeast and transplant it into Mycoplasma capricolum (2). Eric Gaucher of the Georgia Institute of Technology combined phylogeny reconstruction with gene synthesis to express “ancestor proteins.” Using EF-Tu as a molecular thermometer, he analyzed the melting temperature of specific reconstituted ancestor proteins, which pointed to a possible thermophilic origin of life.

For more information

• The meeting program and slides from several of the lectures can be found here.

•To learn more about systems biology, check out the Journal of Biological Chemistry thematic minireview series, “Computational Biochemistry: Systems Biology."

The afternoon continued with an “origin of life” theme as Armen Mulkidjanian of Universitat of Osnabruck presented evidence for his “zinc world hypothesis,” in which photosynthesizing ZnS precipitating around primeval hot springs in high-pressure environments could have driven the synthesis of organic molecules (3). Other afternoon talks covered a range of topics: Frederic F. Pio of Simon Fraser University talked about automated long range homology algorithms, network analysis and experimental methods used to identify the “inflammasome,” and Georgy P. Karev of the National Institutes of Health presented a modification of the Eigen “error catastrophy” model that would allow biological systems to evolve. Literature mining was at the core of the Medscan platform Ilya Mazo of Ariadne Inc. designed to infer relationships between genes and/or compounds using scattered and non-homogeneous literature sources. The afternoon ended with Peter D. Karp of SRI International presenting the Pathway Tools platform.


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