Roger Brent

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Roger Brent
Roger Brent(2).jpg
Roger Brent in his Lab at Fred Hutchinson Cancer Research Center
Born(1955-12-28)December 28, 1955
Spartanburg, South Carolina, US
Alma mater
Known forDomain structure of transcription regulators, systems biology
Scientific career
FieldsBiologist
Institutions
Thesis Regulation of the cellular response to DNA damage (1982)
Website http://brentlab.fredhutch.org/brent/en.html

Roger Brent (born December 28, 1955) is an American biologist known for his work on gene regulation and systems biology. He studies the quantitative behaviors of cell signaling systems and the origins and consequences of variation in them. He is Full Member in the Division of Basic Sciences at the Fred Hutchinson Cancer Research Center and an Affiliate Professor of Genome Sciences at the University of Washington.

Contents

Early life

Brent grew up in Hattiesburg, Mississippi and received his BA in Computer Science and Statistics from the University of Southern Mississippi, where he applied AI techniques to protein folding. He performed PhD (1982) [1] and postdoctoral work (1985) in Biochemistry and Molecular Biology at Harvard University in the laboratory of Mark Ptashne. In work there he cloned the E. coli LexA repressor and showed how it controlled the cell's response to DNA damage, used LexA as a repressor in yeast, [2] [3] and created fusion proteins that used LexA to bring portions of yeast Gal4 and other transcription regulatory proteins to synthetic reporter genes in yeast. [4] These domain swap experiments established the domain structure of eukaryotic transcription regulatory proteins. [5] [6] [7] [8]

Career

Brent's use of prokaryotic repressor proteins in eukaryotes, and development of chimeric proteins containing prokaryotic DNA binding domains, enabled identification of other transcription regulatory domains [9] and gene regulatory technologies including tetracycline-repressor controlled transcriptional repression [10] and the Gal4 and LexA UAS systems used in other model organisms. [11] The use of DNA binding domains to target tethered functional protein domains (for example double strand endonucleases [12] and DNA methylases [13] ) or bait moieties in two-hybrid experiments to defined sites on DNA is now routine.

In 1985, Brent moved to the Department of Molecular Biology at Massachusetts General Hospital and the Department of Genetics at Harvard Medical School. His work there contributed to two-hybrid methods and to development of large scale/ general purpose functional genomic means (interaction mating [14] and development of peptide aptamers) to detect and disrupt protein-protein interactions. [15] In 1997, with Sydney Brenner he helped establish the Molecular Sciences Institute, [16] a nonprofit research laboratory in Berkeley, California, and became its CEO, [17] research director and president in 2001. He initiated his lab's studies on cell signal control and cell-to-cell variation there. He is now a Professor of Basic Sciences at the Fred Hutchinson Cancer Center and an Affiliate Professor of Genome Sciences and Bioengineering at the University of Washington.

Brent's work pursues two main questions: how cell signaling systems control their signals and the information those transmit [18] [19] and the origins and phenotypic consequences of cell-to-cell variation in signaling and subsequent responses. [20]

In 1987, Brent help found, and continues to contribute to, Current Protocols in Molecular Biology, a "how to clone it manual" [21] which started the Current Protocols journals. From 1995 to 2000 he organized the "After the Genome" workshops in Santa Fe, whose content contributed to some of the early systems biology agenda. [22] In addition to customary advisory work with NIH, NSF, and industrial organizations, in 1997 he began to advise the US government on tactical and strategic considerations for defense against biological attack and emerging diseases. [23] [24] [25] [26] In 1998, at the Molecular Sciences Institute, he participated in discussions with Rob Carlson and Drew Endy that helped develop some of the ideas underpinning synthetic biology. [27] From 2011 to 2014 he directed the Center for Biological Futures, an experimental effort to better understand the impacts of advances in biological knowledge and capability on human affairs. [28]

He has been a scholar of The Pew Charitable Trusts [29] and a senior scholar of the Ellison Medical Foundation. [30] In 2003 he shared the Gabbay Award in Biotechnology and Medicine for his work on protein interaction methods, [31] and in 2011 he was named a Fellow of the American Association for the Advancement of Science "for outstanding contributions in the area of biochemistry, transcription, genomics, and systems biology." [32]

Brent's use of prokaryotic repressor proteins and use of them in chimeric proteins to regulate gene expression in eukaryotes was the subject of basic patents (including U.S. Patent 4,833,080 , Regulation of Eukaryotic Gene Expression, with Mark Ptashne). Dr. Brent is the inventor on 16 additional US patents and four pending US patents. [33]

Personal

In 2006, Brent married biologist and 2004 Nobel Prize in Physiology or Medicine laureate Linda B. Buck. [34]

Related Research Articles

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Enterobacteria phage λ is a bacterial virus, or bacteriophage, that infects the bacterial species Escherichia coli. It was discovered by Esther Lederberg in 1950. The wild type of this virus has a temperate life cycle that allows it to either reside within the genome of its host through lysogeny or enter into a lytic phase, during which it kills and lyses the cell to produce offspring. Lambda strains, mutated at specific sites, are unable to lysogenize cells; instead, they grow and enter the lytic cycle after superinfecting an already lysogenized cell.

<span class="mw-page-title-main">Transcription factor</span> Protein that regulates the rate of DNA transcription

In molecular biology, a transcription factor (TF) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are 1500-1600 TFs in the human genome. Transcription factors are members of the proteome as well as regulome.

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In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splicing to create monocistronic mRNAs that are translated separately, i.e. several strands of mRNA that each encode a single gene product. The result of this is that the genes contained in the operon are either expressed together or not at all. Several genes must be co-transcribed to define an operon.

In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control of when the gene is transcribed. This control allows the cell or organism to respond to a variety of intra- and extracellular signals and thus mount a response. Some examples of this include producing the mRNA that encode enzymes to adapt to a change in a food source, producing the gene products involved in cell cycle specific activities, and producing the gene products responsible for cellular differentiation in multicellular eukaryotes, as studied in evolutionary developmental biology.

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<span class="mw-page-title-main">Regulation of gene expression</span> Modifying mechanisms used by cells to increase or decrease the production of specific gene products

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<span class="mw-page-title-main">Primary transcript</span> RNA produced by transcription

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<span class="mw-page-title-main">Repressor</span> Sort of RNA-binding protein in molecular genetics

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<span class="mw-page-title-main">Two-hybrid screening</span> Molecular biology technique

Two-hybrid screening is a molecular biology technique used to discover protein–protein interactions (PPIs) and protein–DNA interactions by testing for physical interactions between two proteins or a single protein and a DNA molecule, respectively.

<span class="mw-page-title-main">Gene</span> Sequence of DNA or RNA that codes for an RNA or protein product

In biology, the word gene can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and non-coding genes.

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<span class="mw-page-title-main">Eukaryotic transcription</span> Transcription is heterocatalytic function of DNA

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<span class="mw-page-title-main">Mark Ptashne</span>

Mark Ptashne is a molecular biologist. He is the Ludwig Chair of Molecular Biology at Memorial Sloan–Kettering Cancer Center in New York City.

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References

  1. ↑ "Regulation of the cellular response to DNA damage" (1982)
  2. ↑ Brent, Roger; Ptashne, Mark (1984). "A bacterial repressor protein or a yeast transcriptional terminator can block upstream activation of a yeast gene". Nature . 312 (5995): 612–615. Bibcode:1984Natur.312..612B. doi:10.1038/312612a0. PMID   6390216. S2CID   4309764.
  3. ↑ North, G. (1984). "Latterday lessons of lambda and lac". Nature. 308 (5961): 687–688. doi: 10.1038/308687a0 . PMID   6232462. S2CID   4240047.
  4. ↑ Brent, Roger; Ptashne, Mark (1985). "A eukaryotic transcriptional activator bearing the DNA specificity of a prokaryotic repressor". Cell . 43 (3): 729–736. doi: 10.1016/0092-8674(85)90246-6 . PMID   3907859.
  5. ↑ Alberts, A.; Bray, D.; Lewis, J.; Raff, M.; Roberts, K. (1989). "Membrane Structure". Molecular Biology of The Cell (6th ed.). Garland Science. p. 568: Figure 10–24. ISBN   978-0-8153-4432-2.
  6. ↑ Frankel, A. D.; Kim, P. S. (1991). "Modular Structure of Transcription Factors: Implications for Gene Regulation". Cell. 65 (5): 717–719. doi:10.1016/0092-8674(91)90378-c. PMID   2040012. S2CID   6632853.
  7. ↑ "Genetics: Lecture 21" (PDF). MIT OpenCourseWare . Massachusetts Institute of Technology. hdl:1721.1/34953. Archived (PDF) from the original on May 18, 2020. Retrieved December 15, 2014.
  8. ↑ Grotewold, E.; Kellogg, E.; Chappell, L (June 2015). Plant Genes, Genomes and Genetics (1st ed.). John Wiley and Sons. ISBN   978-1-119-99887-7.
  9. ↑ Godowski, P. J.; Picard, D.; Yamamoto, K. R. (August 1988). "Signal transduction and transcriptional regulation by glucocorticoid receptor-LexA fusion proteins". Science. 241 (4867): 812–816. Bibcode:1988Sci...241..812G. doi:10.1126/science.3043662. PMID   3043662.
  10. ↑ Deuschle, U.; Meyer, W. K.; Thiesen, H. J. (April 1995). "Tetracycline-reversible silencing of eukaryotic promoters". Molecular Cell Biology. 15 (4): 1907–1914. doi:10.1128/mcb.15.4.1907. PMC   230416 . PMID   7891684.
  11. ↑ Rodriguez, A. D. V; Didaniol, D.; Desplan, C. (2012). "Power tools for gene expression and clonal analysis in Drosophila". Nature Methods. 9 (1): 47–55. doi:10.1038/nmeth.1800. PMC   3574576 . PMID   22205518.
  12. ↑ Bibikova, M. J.; Carroll, D.; Segal, D. J.; Trautman, J.K.; Smith, J.; Kim, Y. G.; Chandrasegaran, S. (January 2001). "Stimulation of homologous recombination through targeted cleavage by chimeric nucleases". Mol Cell Biol. 21 (1): 289–297. doi:10.1128/MCB.21.1.289-297.2001. PMC   88802 . PMID   11113203.
  13. ↑ van Steensel, B.; Henikoff, S. (April 2000). "Identification of in vivo DNA targets of chromatin proteins using tethered dam methyltransferase". Nat. Biotechnol. 18 (4): 424–428. doi:10.1038/74487. PMID   10748524. S2CID   30350384.
  14. ↑ Finley, Jr, R. L. Jr.; and Brent, R. (1994). "Interaction mating reveals binary and ternary interactions between Drosophila cell cycle regulators". Proc. Natl. Acad. Sci. USA. 91 (26): 12980–12984. doi: 10.1073/pnas.91.26.12980 . PMC   45564 . PMID   7809159.
  15. ↑ Brent, Roger; Ptashne, Mark. "Regulation of eukaryotic gene expression US Patent 4,833,080 (1989)" . Retrieved January 6, 2015.
  16. ↑ Friedberg, Errol (October 2010). Sydney Brenner: A Biography. CSHL Press. ISBN   978-0-87969-947-5.
  17. ↑ "Proteomics: Current State and Future Directions - An interview with Roger Brent, PhD" . Retrieved July 5, 2010.
  18. ↑ Yu, R.; Gordon, A.; Colman-Lerner, A.; Benjamin, K. R.; Pincus, D.; Serra, E.; Holl, M.; Brent, R. (2008). "Negative feedback optimizes information transmission in a cell signaling system". Nature. 456 (7223): 755–761. doi:10.1038/nature07513. PMC   2716709 . PMID   19079053.
  19. ↑ Brent, R (2009). "What is the signal and what information does it carry?". FEBS Letters . 583 (24): 4019–24. doi:10.1016/j.febslet.2009.11.029. PMID   19917282. S2CID   15873809.
  20. ↑ Colman-Lerner, A.; Gordon, A.; Serra, E.; Holl, E.; Brent, R. (2005). "Regulated cell-to-cell variation in a cell fate decision system". Nature. 437 (7059): 699–706. Bibcode:2005Natur.437..699C. doi:10.1038/nature03998. PMID   16170311. S2CID   4398874.
  21. ↑ Ausubel, F. M.; Brent, R.; Kingston, R. E.; Moore, D. D.; Seidman, J. G.; Smith, J. A.; Struhl, K (2012). "Preface". Current Protocols in Molecular Biology . Vol. 98. pp. iii–v. doi: 10.1002/0471142727.mbprefs98 . ISBN   978-0-471-14272-0. S2CID   221604713.
  22. ↑ Gruber, M. "Map the Genome, Hack the Genome". Wired.com . Retrieved 2 February 2010.
  23. ↑ Marshall, E. (1997). "Too radical for NIH? Try DARPA". Science . 275 (5301): 744–746. doi:10.1126/science.275.5301.744. PMID   9036531. S2CID   5825319.
  24. ↑ Miller, J.; Broad, W. J.; Engelberg, S. (2001). Germs: Biological Weapons and America's Secret War . New York: Simon and Schuster. ISBN   978-0-684-87159-2.
  25. ↑ Bhattacharjee, Y. (2007). "Panel Provides Peer Review of Intelligence Research". Science. 318 (5856): 1538. doi: 10.1126/science.318.5856.1538 . PMID   18063763. S2CID   41060126.
  26. ↑ Brent, R. (2006-11-22). In the valley of the shadow of death. DSpace@MIT (Draft). hdl:1721.1/34914.
  27. ↑ Carlson, R; et al. "BIO-IO Components and Design Tools" (PDF). Retrieved 5 August 2010.
  28. ↑ Woodward, Kristin (2011-10-13). "Center for biological futures to address challenges posed by explosion of biological knowledge in 21st century". Fred Hutchinson Cancer Research Center. Fred Hutchinson Cancer Research Center . Retrieved 6 January 2014.
  29. ↑ "Pew Scholars Program in the Bio-Medical Sciences". The PEW Charitable Trusts. Retrieved 10 October 2011.
  30. ↑ "HOME::Senior Scholar Award in Aging::2000::Stem Cells". The Ellison Medical Foundation. The Ellison Medical Foundation . Retrieved 8 August 2011.
  31. ↑ "PAST WINNERS 2003 "for their development of yeast two-hybrid and yeast mating interaction traps"". Rosenstiel Basic Medical Sciences Research Center. Brandeis University Rosenstiel Basic Medical Sciences Research Center. Retrieved 13 June 2012.
  32. ↑ Sausville, E. A. (2011). "Awards, Appointments, Announcements". J Natl Cancer Inst . 103 (4): 295. doi: 10.1093/jnci/djr038 .
  33. ↑ "Patent search at USPTO.gov" . Retrieved December 20, 2022.
  34. ↑ Badge, Peter (2008). Nobel Faces. John Wiley & Sons. p. 180. ISBN   978-3-527-40678-4 . Retrieved December 2, 2015.
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