Susan Golden

Susan S. Golden
Nationality American
Alma mater B.A. in Biology from Mississippi University for Women (1978), Ph.D. in Genetics from the University of Missouri (1983)
Scientific career
Fields Chronobiology, Bioengineering
Institutions University of Chicago (1983), Texas A&M University (1986), UCSD Division of Biological Sciences (2008)

Susan Golden (née Stephens) was born in Pine Bluff, Arkansas in 1957.[1] She attended the local public high school, where she was involved with the marching band and school newspaper. She was accepted to the Mississippi University for Women in 1976 as a journalism major, but soon after switched to a major in biology and a minor in chemistry.

Golden graduated from MUW in two years, after which she was offered a position in the first cohort of trainees in an NIH-financed doctoral program in genetics at the University of Missouri. During her graduate program Golden met her husband, James Golden, another student in the NIH program.[2] They married in 1979. At the University of Missouri Golden researched the protein makeup of the photosynthetic center in cyanobacteria, work she continued when she moved to the University of Chicago in 1983 as an NIH postdoctoral research fellow.[1]

In 1986 Golden accepted a faculty position at Texas A&M to further her investigation into light-dependent gene regulation in bacteria. It was at Texas A&M that Golden was first put into contact with Drs. Carl H. Johnson and Takao Kondo (the two other researchers responsible for the discovery of the Kai complex) and first became interested in studying circadian rhythms.[2] Dr. Golden was promoted to Distinguished Professor at Texas A&M in 2003, and then moved to UCSD in 2008 where she is currently a Distinguished Professor and the Director of the Center for Circadian Biology.[3]

Research Contributions

Early Work

Dr. Golden began her graduate career in the lab of Dr. Louis A. Sherman, where she worked on developing genetic approaches to research the protein makeup of the photosynthetic complexes of the cyanobacteria Synechoccus elongatus. Golden was the first to demonstrate that a mutant allele of the psbA gene is sufficient to confer herbicide resistance in cyanobacteria.[2] Other research later confirmed that this gene coded for a protein integral to the photosynthetic Photosystem II complex.[4] These findings also demonstrated that genetic manipulation of cyanobacteria was straightforward, opening up S. elongatus as a model organism for future genetic experiments.[2] During her postdoctoral research at the University of Chicago, in the lab of Dr. Robert Haselkorn, Dr. Golden continued to work on developing genetic manipulation techniques for Synechoccus elongatus in order to elucidate mechanisms of gene regulation in photosynthesis genes. In 1989, Dr. Golden's team discovered that the specific psbA allele expressed by cyanobacteria depended on the lighting conditions in which the colony was grown.[5] This finding led her to investigate more generally how light influenced expression of photosynthetic genes in the organism,[6] and contributed to the overall understanding of bacterial responses to environmental input.[7] This line of inquiry necessitated the development of a technique for visualizing changes in gene expression in living organisms. While a professor at the Texas A&M, Golden attempted to solve this problem by attaching a luciferase gene to the promoters of the cyanobacterial genes of interest and viewing the colonies with a night vision scope.[2] The approach was a success, allowing for quantification of cyanobacterial gene expression in vivo over an extended time period. This technique drew the interest of chronobiologist Dr. Carl H. Johnson, with whom Dr. Golden would go on to collaborate in the discovery of the KaiABC complex .[2]

Discovery of Kai Complex

Golden studies the endogenous rhythms of cyanobacteria, a group of prokaryotes shown to have circadian clocks. She transformed Synechococcus elongatus, one of the better studied models, with a luciferase reporter gene and showed circadian rhythm in bioluminescence. This was used to discover the cyanobacterial clock, based on three proteins, KaiA, KaiB, and KaiC. In collaboration with Carl H. Johnson and Takao Kondo, she demonstrated circadian rhythms in S. elongatus PCC 7942,[8] the only model organism for a prokaryotic circadian clock.[3] Susan Golden is identifying genes in the S. elongatus genome that contribute to circadian rhythm through reverse genetics, creating a mutation in a gene and screening for mutant phenotypes. Transposons are inserted to recombine in the genome, producing a gene knockout.[3] In one study, nineteen clock mutations were mapped to the three kai genes, and the inactivation of any single kai gene abolished the circadian rhythm of expression of KaiA and KaiB and reduced kaiBC-promoter activity.[9]

The Kai Protein Circadian System

S. elongatus has a circadian clock with an oscillator based only on three proteins, KaiA, KaiB, and KaiC where rhythm is generated based on KaiC phosphorylation and dephosphorylation in vitro. Photosynthesis is used to send light information, leading to clock-controlled outputs affecting transcription. This 24-hour rhythm can be recreated in vitro with the addition of ATP.[10] The ratio of ATP/ADP fluctuates during the course of the day, and is sensed by KaiC, which phosphorylates or de-phosphorylates based on this signal. This Kai protein system is the simplest post-translational oscillator known so far.

In photosynthesizing cyanobacteria, light drives the clock and darkness resets it. When Golden mutated the gene cikA, the clock could not be reset, (resulting in permanent jet lag), but the clock still functioned. CikA contained a protein domain that resembled KaiA, which was also found to be important in resetting the clock. CikA and KaiA bind to quinones, which carry electrons in the electron transport chain of photosynthesis. Quinones are oxidized in the dark and reduced in the light, and the redox state affects KaiA activity. When quinones are oxidized, KaiA separates from KaiC and binds to them, resetting the clock. Therefore, quinones are essential in transmitting light information to KaiC.[2]

Current Research

Metabolic Engineering

After moving to UCSD in 2008, Susan Golden's research converged with that of her husband, James Golden, to investigate biofuels.[2] She is conducting research that investigates the usage of cyanobacteria for industrial purposes. Cyanobacteria are an attractive model organism due to simplistic genomes and their use of photosynthesis, and they could be used to replace petroleum fuels in the future through generation of biofuels.[3] Cyanobacteria also grow fast and fix atmospheric carbon, converting carbon dioxide into biomass, which can then be converted to bio-oils and biofuels. They only require sunlight, water and inorganic trace elements for growth, and direct fixation of carbon for biofuels.[11]

In 2016, Golden and colleagues manually curated a model of metabolism in S. elongates, indicating the importance of a linear TCA (tricarboxylic acid cycle) pathway and the discovery of a model for the basis of metabolic design.[12]

Honors and Awards[2]

  • National Science Foundation Presidential Young Investigator Award, 1989 to 1995
  • Fellowship in the American Academy of Microbiology, 2000
  • Texas A&M Distinguished Professor, 2003
  • Member of the Faculty of 1000 Biology
  • Member of the National Academy of Sciences
  • Howard Hughes Medical Institute Professor
  • UC San Diego Distinguished Professor and Chancellor’s Associates Chair
  • Honma Prize Winner (2018)

Selected publications

  • Kondo T, Strayer CA, Kulkarni RD, Taylor W, Ishiura M, Golden SS, Johnson CH (1993). "Circadian rhythms in prokaryotes: luciferase as a reporter of circadian gene expression in cyanobacteria". Proc Natl Acad Sci USA. 90 (12): 5672–6. PMID 8516317.
  • Kondo T, Tsinoremas NF, Golden SS, Johnson CH, Kutsuna S, Ishiura M (1994). "Circadian clock mutants of cyanobacteria". Science. 266 (5188): 1233–6. PMID 7973706.
  • Liu Y, Golden SS, Kondo T, Ishiura M, Johnson CH (1995). "Bacterial luciferase as a reporter of circadian gene expression in cyanobacteria". J Bacteriol. 177 (8): 2080–6. PMID 7536731.
  • Golden SS (1995). "Light-responsive gene expression in cyanobacteria". J Bacteriol. 177 (7): 1651–4. PMID 7896684.
  • Liu Y, Tsinoremas NF, Johnson CH, Lebedeva NV, Golden SS, Ishiura M, Kondo T (1995). "Circadian orchestration of gene expression in cyanobacteria". Genes Dev. 9 (12): 1469–78. PMID 7601351.
  • Tsinoremas NF, Ishiura M, Kondo T, Andersson CR, Tanaka K, Takahashi H, Johnson CH, Golden SS (1996). "A sigma factor that modifies the circadian expression of a subset of genes in cyanobacteria". EMBO J. 15 (10): 2488–95. PMID 8665856.
  • Johnson CH, Golden SS, Ishiura M, Kondo T (1996). "Circadian clocks in prokaryotes". Mol Microbiol. 21 (1): 5–11. PMID 8843429.
  • Kondo T, Mori T, Lebedeva NV, Aoki S, Ishiura M, Golden SS (1997). "Circadian rhythms in rapidly dividing cyanobacteria". Science. 275 (5297): 224–7. PMID 8985018.
  • Golden SS, Ishiura M, Johnson CH, Kondo T (1997). "Cyanobacterial circadian rhythms". Annu Rev Plant Physiol Plant Mol Biol. 48: 327–354. PMID 15012266.
  • Ouyang Y, Andersson CR, Kondo T, Golden SS, Johnson CH (1998). "Resonating circadian clocks enhance fitness in cyanobacteria". Proc Natl Acad Sci USA. 95 (15): 8660–4. PMID 9671734.
  • Ishiura M, Kutsuna S, Aoki S, Iwasaki H, Andersson CR, Tanabe A, Golden SS, Johnson CH, Kondo T (1998). "Expression of a gene cluster kaiABC as a circadian feedback process in cyanobacteria". Science. 281 (5382): 1519–23. PMID 9727980.
  • Johnson CH, Golden SS, Kondo T (1998). "Adaptive significance of circadian programs in cyanobacteria". Trends Microbiol. 6 (10): 407–10. PMID 9807785.
  • Golden SS, Johnson CH, Kondo T (1998). "The cyanobacterial circadian system: a clock apart". Curr Opin Microbiol. 1 (6): 669–73. PMID 10066545.
  • Katayama M, Tsinoremas NF, Kondo T, Golden SS (1999). "cpmA, a gene involved in an output pathway of the cyanobacterial circadian system". J Bacteriol. 181 (11): 3516–24. PMID 10348865.
  • Johnson CH, Golden SS (1999). "Circadian programs in cyanobacteria: adaptiveness and mechanism". Annu Rev Microbiol. 53: 389–409. PMID 10547696.
  • Andersson CR, Tsinoremas NF, Shelton J, Lebedeva NV, Yarrow J, Min H, Golden SS (2000). "Application of bioluminescence to the study of circadian rhythms in cyanobacteria". Methods Enzymol. 305: 527–42. PMID 10812624.
  • Williams SB, Vakonakis I, Golden SS, LiWang AC (2002). "Structure and function from the circadian clock protein KaiA of Synechococcus elongatus: a potential clock input mechanism". Proc Natl Acad Sci USA. 99 (24): 15357–62. PMID 12438647.
  • Ditty JL, Williams SB, Golden SS (2003). "A cyanobacterial circadian timing mechanism". Annu Rev Genet. 37: 513–43. PMID 14616072.
  • Golden SS (2003). "Timekeeping in bacteria: the cyanobacterial circadian clock". Curr Opin Microbiol. 6 (6): 535–40. PMID 14662347.
  • Golden SS (2004). "Meshing the gears of the cyanobacterial circadian clock". Proc Natl Acad Sci USA. 101 (38): 13697–8. PMID 15367731.
  • Mackey SR, Golden SS (2007). "Winding up the cyanobacterial circadian clock". Trends Microbiol. 15 (9): 381–8. PMID 17804240.
  • Kim YI, Dong G, Carruthers CW Jr, Golden SS, LiWang A (2008). "The day/night switch in KaiC, a central oscillator component of the circadian clock of cyanobacteria". Proc Natl Acad Sci USA. 105 (35): 12825–30. doi:10.1073/pnas.0800526105. PMC 2529086. PMID 18728181.
  • Dong G, Golden SS (2008). "How a cyanobacterium tells time". Curr Opin Microbiol. 11 (6): 541–6. doi:10.1016/j.mib.2008.10.003. PMC 2692899. PMID 18983934.
  • Chen Y, Kim YI, Mackey SR, Holtman CK, Liwang A, Golden SS (2009). "A novel allele of kaiA shortens the circadian period and strengthens interaction of oscillator components in the cyanobacterium Synechococcus elongatus PCC 7942". J Bacteriol. 191 (13): 4392–400. doi:10.1128/JB.00334-09. PMID 19395479.
  • Dong G, Yang Q, Wang Q, Kim YI, Wood TL, Osteryoung KW, van Oudenaarden A, Golden SS (2010). "Elevated ATPase activity of KaiC applies a circadian checkpoint on cell division in Synechococcus elongatus". Cell. 140 (4): 529–39. doi:10.1016/j.cell.2009.12.042. PMID 20178745.
  • Dong G, Kim YI, Golden SS (2010). "Simplicity and complexity in the cyanobacterial circadian clock mechanism". Curr Opin Genet Dev. 20 (6): 619–25. doi:10.1016/j.gde.2010.09.002. PMID 20934870.
  • Cohen SE, Golden SS (2015). "Circadian Rhythms in Cyanobacteria". Microbiol Mol Biol Rev. 79 (4): 373–85. doi:10.1128/MMBR.00036-15. PMID 26335718.
  • Rubin BE, Wetmore KM, Price MN, Diamond S, Shultzaberger RK, Lowe LC, Curtin G, Arkin AP, Deutschbauer A, Golden SS (2015). "The essential gene set of a photosynthetic organism". Proc Natl Acad Sci USA. 112 (48): E6634–43. doi:10.1073/pnas.1519220112. PMID 26508635.
  • Tseng R, Goularte NF, Chavan A, Luu J, Cohen SE, Chang YG, Heisler J, Li S, Michael AK, Tripathi S, Golden SS, LiWang A, Partch CL (2017). "Structural basis of the day-night transition in a bacterial circadian clock". Science. 355 (6330): 1174–1180. doi:10.1126/science.aag2516. PMID 28302851.

References

  1. 1 2 "SQ Online / Faculty Spotlight: Dr. Susan Golden". sqonline.ucsd.edu. Retrieved 2017-04-12.
  2. 1 2 3 4 5 6 7 8 9 Gupta, Sujata (2013-05-28). "Profile of Susan S. Golden". Proceedings of the National Academy of Sciences of the United States of America. 110 (22): 8758–8760. doi:10.1073/pnas.1305064110. ISSN 0027-8424. PMC 3670312. PMID 23620521.
  3. 1 2 3 4 "Susan S. Golden". biology.ucsd.edu. Retrieved 2017-04-12.
  4. ↑ Goussias, Charilaos; Boussac, Alain; Rutherford, A William (2002-10-29). "Photosystem II and photosynthetic oxidation of water: an overview". Philosophical Transactions of the Royal Society B: Biological Sciences. 357 (1426): 1369–1420. doi:10.1098/rstb.2002.1134. ISSN 0962-8436. PMC 1693055. PMID 12437876.
  5. ↑ Schaefer, M. R.; Golden, S. S. (1989-05-05). "Light availability influences the ratio of two forms of D1 in cyanobacterial thylakoids". Journal of Biological Chemistry. 264 (13): 7412–7417. ISSN 0021-9258. PMID 2496127.
  6. ↑ http://www.nasonline.org, National Academy of Sciences -. "Susan Golden". www.nasonline.org. Retrieved 2017-04-12.
  7. ↑ Tandeau de Marsac, Nicole; Houmard, Jean (1993-01-01). "Adaptation of cyanobacteria to environmental stimuli: new steps towards molecular mechanisms". FEMS Microbiology Letters. 104 (1–2): 119–189. doi:10.1111/j.1574-6968.1993.tb05866.x. ISSN 0168-6445.
  8. ↑ Cohen, Susan (1 December 2015). "Circadian Rhythms in Cyanobacteria". Microbiology and Molecular Biology Reviews. 79 (4). doi:10.1128/MMBR.00036-15. PMC 4557074. Retrieved 12 April 2017.
  9. ↑ Ishiura, Masahiro; Kutsuna, Shinsuke; Aoki, Setsuyuki; Iwasaki, Hideo; Andersson, Carol R.; Tanabe, Akio; Golden, Susan S.; Johnson, Carl H.; Kondo, Takao (1998-09-04). "Expression of a Gene Cluster kaiABC as a Circadian Feedback Process in Cyanobacteria". Science. 281 (5382): 1519–1523. doi:10.1126/science.281.5382.1519. ISSN 0036-8075. PMID 9727980.
  10. ↑ Dong, Guogang (10 November 2008). "How a Cyanobacterium Tells Time". Current Opinion in Microbiology. 11 (6). doi:10.1016/j.mib.2008.10.003. PMC 2692899.
  11. ↑ Sarsekeyeva, Fariza (22 February 2015). "Cyanofuels: biofuels from cyanobacteria. Reality and perspectives". Photosynthesis Research. 125 (1): 325–340. doi:10.1007/s11120-015-0103-3. Retrieved 26 April 2017.
  12. ↑ Broddrick, Jared T.; Rubin, Benjamin E.; Welkie, David G.; Du, Niu; Mih, Nathan; Diamond, Spencer; Lee, Jenny J.; Golden, Susan S.; Palsson, Bernhard O. (2016-12-20). "Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis". Proceedings of the National Academy of Sciences. 113 (51): E8344–E8353. doi:10.1073/pnas.1613446113. ISSN 0027-8424. PMC 5187688. PMID 27911809.
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