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Susan S. Golden

Research

Circadian Rhythms of Gene Expression in Cyanobacteria

Cells of diverse organisms, from cyanobacteria to humans, use a circadian (24 h) clock to control physiological events and gene expression. The circadian clock of the cyanobacterium Synechococcus elongatus is a discrete nanomachine comprising three proteins — KaiA, KaiB, and KaiC — which interact progressively to set up the timekeeping mechanism, and two kinases whose activities are altered by engaging the Kai oscillator. Our research focuses on understanding the key events that enable the clock to tell time, become set to local time, and regulate global patterns of gene expression and metabolism. To address these research questions we use approaches of molecular genetics, genomics, and biochemistry, and work closely with structural biologists.

Functional Genomics in S. elongatus

The easy genetic manipulation of S. elongatus provides many strategies to understand the function and regulation of its genome. In addition to a suite of genetic tools that enable gene inactivation and overexpression and use of reporter genes, we employ a dense bar-coded transposon library that enables the fitness of thousands of mutants to be assessed in a population under specific test conditions. This strategy helps to identify unknown genes that contribute to phenotypes of interest by an unbiased, quick, and inexpensive method.

Metabolic Engineering of Cyanobacteria for the production of Molecules of Interest

Because cyanobacteria grow photosynthetically using water and CO 2 and are easy to manipulate genetically, they are attractive organisms for the production of molecules that have industrial applications. Through development of genetic tools, support of a metabolic model, and characterization of different growth modes such as biofilm formation, we seek to improve the prospects for cyanobacteria as industrial production platforms.

Select Publications

  • Reconstitution of an intact clock reveals mechanisms of circadian timekeeping. Chavan AG, Swan JA, Heisler J, Sancar C, Ernst DC, Fang M, Palacios JG, Spangler RK, Bagshaw CR, Tripathi S, Crosby P, Golden SS, Partch CL, LiWang A. Science. 2021 Oct 8;374(6564):eabd4453. doi: 10.1126/science.abd4453. Epub 2021 Oct 8. PMID: 34618577
  • The circadian clock and darkness control natural competence in cyanobacteria. Taton A, Erikson C, Yang Y, Rubin BE, Rifkin SA, Golden JW, Golden SS. Nat Commun. 2020 Apr 3;11(1):1688. doi: 10.1038/s41467-020-15384-9. PMID: 32245943
  • A Cyanobacterial Component Required for Pilus Biogenesis Affects the Exoproteome. Yegorov Y, Sendersky E, Zilberman S, Nagar E, Waldman Ben-Asher H, Shimoni E, Simkovsky R, Golden SS, LiWang A, Schwarz R. mBio. 2021 Mar 16;12(2):e03674-20. doi: 10.1128/mBio.03674-20. PMID: 33727363
  • A microcin processing peptidase-like protein of the cyanobacterium Synechococcus elongatus is essential for secretion of biofilm-promoting proteins. Parnasa R, Sendersky E, Simkovsky R, Waldman Ben-Asher H, Golden SS, Schwarz R. Environ Microbiol Rep. 2019 Jun;11(3):456-463. doi: 10.1111/1758-2229.12751. Epub 2019 Mar 29. PMID: 30868754
  • Yang Y, Lam V, Adomako M, Simkovsky R, Jakob A, Rockwell NC, Cohen SE, Taton A, Wang J, Lagarias JC, Wilde A, Nobles DR, Brand JJ, Golden SS. Phototaxis in a wild isolate of the cyanobacterium Synechococcus elongatus. Proc Natl Acad Sci U S A. 2018 Dec 14. pii: 201812871. doi: 10.1073/pnas.1812871115. [Epub ahead of print] PMID: 30552139
  • Broddrick JT, Welkie DG, Jallet D, Golden SS, Peers G, Palsson BO. Predicting the metabolic capabilities of Synechococcus elongatus PCC 7942 adapted to different light regimes. Metab Eng. 2018 Nov 13;52:42-56. doi: 10.1016/j.ymben.2018.11.001. [Epub ahead of print] PMID: 30439494
  • Cohen SE, McKnight BM, Golden SS. Roles for ClpXP in regulating the circadian clock in Synechococcus elongatus. Proc Natl Acad Sci U S A. 2018 Aug 14;115(33):E7805-E7813. doi: 10.1073/pnas.1800828115. Epub 2018 Jul 30. PMID: 30061418
  • Welkie DG, Rubin BE, Chang YG, Diamond S, Rifkin SA, LiWang A, Golden SS. Genome-wide fitness assessment during diurnal growth reveals an expanded role of the cyanobacterial circadian clock protein KaiA. Proc Natl Acad Sci U S A. 2018 Jul 24;115(30):E7174-E7183. doi: 10.1073/pnas.1802940115. Epub 2018 Jul 10. PMID: 29991601
  • Rubin BE, Huynh TN, Welkie DG, Diamond S, Simkovsky R, Pierce EC, Taton A, Lowe LC, Lee JJ, Rifkin SA, Woodward JJ, Golden SS. High-throughput interaction screens illuminate the role of c-di-AMP in cyanobacterial nighttime survival. PLoS Genet. 2018 Apr 2;14(4):e1007301. doi: 10.1371/journal.pgen.1007301. eCollection 2018 Apr. PMID: 29608558
  • Taton, A., A.T. Ma, M. Ota M, S.S. Golden, and Golden JW. 2017. NOT gate genetic circuits to control gene expression in cyanobacteria. ACS Synth Biol. 2017 Aug 21. doi:10.1021/acssynbio.7b00203. [Epub ahead of print
  • Nagar E., S. Zilberman, E. Sendersky, R. Simkovsky, E. Shimoni, D. Gershtein, M. Herzberg, S.S. Golden, and R. Schwarz R. 2017. Type 4 pili are dispensable for biofilm development in the cyanobacterium Synechococcus elongatus. Environ Microbiol. 2017 Jun 5. doi: 10.1111/1462-2920.13814. [Epub ahead of print]
  • Tseng R., N.F. Goularte, A. Chavan, J. Luu, S.E. Cohen, Y.-G. Chang, J. Heisler, S. Li, A.K. Michael, S. Tripathi, S.S. Golden, A. LiWang., and C.L. Partch. 2017. Structural basis of the day-night transition in a bacterial circadian clock. Science. Mar 17;355(6330):1174-1180. doi: 10.1126/science.aag2516. Epub 2017 Mar 16.
  • Diamond S, Rubin BE, Shultzaberger RK, Chen Y, Barber CD, Golden SS. 2017. Redox crisis underlies conditional light-dark lethality in cyanobacterial mutants that lack the circadian regulator, RpaA. Proc Natl Acad Sci U S A. 2017 Jan 10. pii: 201613078. doi: 10.1073/pnas.1613078114. [Epub ahead of print] PMID: 28074036
  • Broddrick JT, Rubin BE, Welkie DG, Du N, Mih N, Diamond S, Lee JJ, Golden SS, Palsson BO. 2016. Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis. Proc Natl Acad Sci U S A. 2016 Dec 20;113(51):E8344-E8353. doi: 10.1073/pnas.1613446113. PMID: 27911809

Biography

Susan Golden received a B.A. (1978) in Biology from Mississippi University for Women and a Ph.D. (1983) in Genetics from the University of Missouri. After postdoctoral research at the University of Chicago, she joined the faculty of Biology at Texas A&M University (1986), where she was promoted to Distinguished Professor in 2003. She joined the Division of Biological Sciences at UCSD in 2008.

During her graduate work she developed genetic tools for the cyanobacterium Synechococcus elongatus (PCC 7942), the first cyanobacterium shown to be subject to genetic transformation. This led to work on regulation of light-responsive photosynthesis gene expression in this organism during her postdoctoral research and at Texas A&M. In the early 1990s she began a collaborative project with C.H. Johnson (Vanderbilt University) and T. Kondo (Nagoya University) that demonstrated circadian rhythms of gene expression in S. elongatus, which is currently the premier model organism for a prokaryotic circadian clock. The molecular basis of timekeeping in S. elongatus is now a major focus of her lab. Susan is a Fellow of the American Academy of Microbiology and an Member of the National Academy of Sciences.

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