Roger Brent

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.

Roger Brent
Roger Brent in his Lab at Fred Hutchinson Cancer Research Center
Born	(1955-12-28)December 28, 1955 Spartanburg, South Carolina, US
Alma mater	University of Southern Mississippi Harvard University
Known for	Domain structure of transcription regulators, systems biology
Scientific career
Fields	Biologist
Institutions	Harvard University Molecular Sciences Institute Fred Hutchinson Cancer Research Center
Thesis	Regulation of the cellular response to DNA damage  (1982)
Website	http://brentlab.fredhutch.org/brent/en.html

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]

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. (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.