Steven A. Benner

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Dr. Steven Benner
Nationality United States
Fields Chemistry, synthetic biology
Institutions Harvard University
University of Florida
Alma mater Yale University
Harvard University
Doctoral advisor Robert Burns Woodward, Frank Westheimer

Steven A. Benner is a former V.T. & Louise Jackson Distinguished Professor of Chemistry at the University of Florida Department of Chemistry. He was also a faculty member in the Department of Molecular Cell Biology.

Benner left University of Florida in late December 2005 to found The Westheimer Institute of Science and Technology (TWIST) in Honor of Frank Westheimer. He also created the Foundation For Applied Molecular Evolution (FFAME).[1]

Benner has also founded EraGen Biosciences [1] and Firebird BioMolecular SCiences LLC.[2]

Benner joined the faculty at the University of Florida in 1997, after working at Harvard University and the Swiss Federal Institute of Technology Zurich. He received his B.S./M.S. in Molecular Biophysics and Biochemistry from Yale University, and his Ph.D. in Chemistry from Harvard University under the supervision of Robert Burns Woodward and Frank Westheimer.[3]

The Benner Laboratory[edit]

The Benner laboratory is an originator of the field of "synthetic biology", which seeks to generate, by chemical synthesis, molecules that reproduce the complex behavior of living systems, including their genetics, inheritance, and evolution. Some high points of past work in chemical genetics are listed below.

Gene synthesis[edit]

In 1984, the Benner laboratory was the first to report the chemical synthesis of a gene encoding an enzyme, following Khorana's synthesis of a shorter gene for tRNA in 1970. This was the first designed gene of any kind, and the design strategies introduced in this synthesis are now widely used to support protein engineering.

Artificial genetic systems[edit]

The Benner laboratory introduced the first expanded DNA alphabets in 1989, and developed these into an Artificially Expanded Genetic Information System (AEGIS),[4] which now has its own supporting molecular biology. AEGIS enables the synthesis of proteins with more than 20 encoded amino acids, and provides insight into how nucleic acids form duplex structures, how proteins interact with nucleic acids, and how alternative genetic systems might appear in non-terran life.

Researchers such as Eric T. Kool, J. Morales, S. Benner, S. Moroney, C. Switzer, K. Tanaka, M. Shinoya and others, have created an extended alphabet of synthetic bases that can be incorporated into DNA (as well as RNA) using Watson-Crick bonding (as well as non-Watson-Crick bonding). While most of these synthetic bases are derrivatives of the A, C, G, T bases, some are different. While some are in Watson-Crick pairs (A/T, C/G), some are self complementing (X/X). Thus the genetic alphabet has been expanded. An example is the xDNA of Eric T. Kool.[5]

The expanded DNA alphabet supports an expanded set of codons: synthetic codons. Thus if codons consist of DNA base triples, the typical 43 = 64 codons is expanded. For example, if there are 9 DNA bases, then there can be 93 = 729 possible codons. For these codons to be useful, then aminoacyl-tRNA synthetase has been created such that tRNA can code for the possibly synthetic amino acid to be coupled with its corresponding synthetic anti-codon. S. Brenner has described such a system which uses synthetic iso-C/iso-G DNA which uses the synthetic DNA codon [iso-C/A/G] which he calls the 65th codon. Synthetic mRNA with synthetic anti-codon [iso-G/U/C] with synthetic aminoacyl-tRNA synthetase results in an in vivo experiment that can code for a synthetic amino acid incorporated into synthetic polypeptides (synthetic proteomics).[6]

Furthermore, synthetic codons using more than 3 bases have been created, that are functional with ribosomes. For example, if codons consisting of 4- or 5-bases are considered, then synthetic biology can be expanded even further. See codons, research by H. Murakami and M. Sisido with medical genetics applications to Duchene/Becker Muscular Dystrophy.

This discussion constitutes part of the subject matter of synthetic biology, a subject that was founded by S. Benner. This research may also be extended to aspects of nanotechnology insofar as DNA is under research in nanotechnology (thus synthetic DNA also), as well as synthetic Biological Warfare.

A "second generation" model for nucleic acids[edit]

The first generation model for nucleic acid structure, proposed by Watson and Crick 50 years ago, has proven inadequate to guide modification of the core structure of DNA. The Benner group has used synthetic organic chemistry and biophysics to create a "second generation" model for nucleic acid structure. The model emphasizes the role of the sugar and phosphate backbone in the genetic molecular recognition event, and creates perspectives on how nucleic acids work, tools for diagnostics and nanotechnology, and insights on how extraterrestrial life might be recognized.

Practical genotyping tools[edit]

The FDA has approved two products that use AEGIS DNA in human diagnostics. These monitor the loads of virus in patients infected with hepatitis C and HIV. AEGIS also enables products developed by EraGen Biosciences[1] for multiplexed detection of genetic markers and single nucleotide polymorphisms in patient samples. These tools will allow personalized medicine using "point-of-care" genetic analysis, as well as research tools that measure the level of individual mRNA molecules within single processes of single living neurons.

Astrobiology[edit]

The exploration of planets other than Earth seeks signs of non-terrean life. The Benner group has worked to identify molecular structures likely to be universal features of living systems regardless of their genesis, and not likely products of non-biological processes. These are "bio-signatures", both for terrean-like life and for "weird" life forms. As a member of the NASA Astrobiology Institute (with the University of Washington), and in collaborations with the Jet Propulsion Laboratory and the University of Michigan, the Benner group is designing the next generation of probes to Mars.[7]

Genomics and Interpretive Proteomics[edit]

Proteins and genes are nothing more (and nothing less) than organic molecules. In the late 1980s, the Benner group recognized that genome sequencing projects would generate sequences for millions of these in the coming decade, offering more molecular structures than then known to organic chemistry. The group developed computational tools to extract chemical and biological information from these. FFAME has registered to compete for the Archon Genomics X-prize [8]

Bioinformatics workbenches and databases[edit]

In 1990, in collaboration with Prof. Gaston Gonnet, the Benner laboratory introduced [9]], the first bioinformatics workbench. DARWIN supported the first exhaustive matching of a modern genomic sequence databases, and generated information that showed how natural proteins divergently evolve under functional constraints by accumulating mutations, insertions, and deletions.[9]

Protein structure prediction[edit]

The Benner laboratory provided the first practical tools to predict the three dimensional structure of proteins from sequence data. This has led to a revolution in tools to model protein folds, detect distant homologs, enable structural genomics, and join protein sequence, structure, and function. Further, the work has suggested limits to structure prediction by homology, defining what can and cannot be done with this strategy.

Interpretive proteomics[edit]

The Benner laboratory introduced a range of "second generation" tools to interpret genomic data. These include tools that analyze patterns of conservation and variation using structural biology, study variation in these patterns across different branches of an evolutionary tree, and correlate events in the genetic record with events in the history of the biosphere known from geology and fossils. From this has emerged examples showing how the roles of biomolecules in contemporary life can be understood through models of the historical past.

Practical interpretive proteomics[edit]

The global proteome is assembled from approximately 100,000 easily recognized families of protein modules. The MasterCatalog, developed in collaboration with EraGen Biosciences,[1] organizes all of these according to their evolutionary histories. Genome Therapeutics Corporation recently selected the Master Catalog as the interpretive proteomics platform to distribute its proprietary microbial sequence database, and the combined product today has over $2 million in annual sales. In addition to offering a manageable version of GenBank, the MasterCatalog supports a variety of evolution-based tools in interpretive proteomics, and suggests therapeutic and diagnostic targets.

Experimental paleogenetics[edit]

For more details on this topic, see Ancestral gene resurrection.

The Benner laboratory was an originator of the field of experimental paleogenetics, where genes and proteins from ancient organisms are resurrected using bioinformatics and recombinant DNA technology. Experimental work on ancient proteins has tested hypotheses about the evolution of complex biological functions, including the biochemistry of ruminant digestion,[10] the thermophily of ancient bacteria, and the interaction between plants, fruits, and fungi at the time of the Cretaceous extinction. These develop our understanding of biological behavior that extends from the molecule to the cell to the organism, ecosystem, and planet.

References[edit]

  1. ^ a b c "EraGen Biosciences". 
  2. ^ "Firebird BioMolecular SCiences LLC". 
  3. ^ "Steven Benner biography at the FFAME". 
  4. ^ Zunyi Yang, Daniel Hutter, Pinpin Sheng, A. Michael Sismour and Steven A. Benner (2006). "Artificially expanded genetic information system: a new base pair with an alternative hydrogen bonding pattern". Nucleic Acids Research 34 (21): 6095–6101. doi:10.1093/nar/gkl633. PMC 1635279. PMID 17074747. 
  5. ^ "Emergent Computation: Emphasizing Bioinformatics", by Matthew Simon, Springer, 2005, pp. 88-98
  6. ^ Simon 2005, pp. 100-106
  7. ^ Davies, PCW Benner, SA Cleland, CE Lineweaver, CH McKay, CP Wolfe-Simon, F (2009). "Signatures of a Shadow Biosphere". Astrobiology 9 (2): 241–249. Bibcode:2009AsBio...9..241D. doi:10.1089/ast.2008.0251. PMID 19292603. 
  8. ^ "Archon X-prize entrant: Foundation for Applied Molecular Evolution". 
  9. ^ a b "DARWIN bioinformatics workbench". 
  10. ^ Steven A. Benner, M. Daniel Caraco, J. Michael Thomson, Eric A. Gaucher (May 2002). "Planetary Biology--Paleontological, Geological, and Molecular Histories of Life". Science 296 (5569): 864–868. Bibcode:2002Sci...296..864B. doi:10.1126/science.1069863. PMID 11988562.