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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

  • Machine learning reveals the transcriptional regulatory network and circadian dynamics of Synechococcus elongatus PCC 7942. Yuan Y, Al Bulushi T, Sastry AV, Sancar C, Szubin R, Golden SS, Palsson BO. Proc Natl Acad Sci U S A. 2024 Sep 17;121(38):e2410492121. doi: 10.1073/pnas.2410492121. Epub 2024 Sep 13. PMID: 39269777
  • A cyanobacterial sigma factor F controls biofilm-promoting genes through intra- and intercellular pathways. Suban S, Yemini S, Shor A, Waldman Ben-Asher H, Yaron O, Karako-Lampert S, Sendersky E, Golden SS, Schwarz R. Biofilm. 2024 Jul 26;8:100217. doi: 10.1016/j.bioflm.2024.100217. eCollection 2024 Dec. PMID: 39188729
  • Synechococcus elongatus Argonaute reduces natural transformation efficiency and provides immunity against exogenous plasmids. Taton A, Gilderman TS, Ernst DC, Omaga CA, Cohen LA, Rey-Bedon C, Golden JW, Golden SS. mBio. 2023 Oct 31;14(5):e0184323. doi: 10.1128/mbio.01843-23. Epub 2023 Oct 4. PMID: 37791787
  • Phenotypically complex living materials containing engineered cyanobacteria. Datta D, Weiss EL, Wangpraseurt D, Hild E, Chen S, Golden JW, Golden SS, Pokorski JK. Nat Commun. 2023 Aug 7;14(1):4742. doi: 10.1038/s41467-023-40265-2. PMID: 37550278
  • Roles for the Synechococcus elongatus RNA-Binding Protein Rbp2 in Regulating the Circadian Clock. McKnight BM, Kang S, Le TH, Fang M, Carbonel G, Rodriguez E, Govindarajan S, Albocher-Kedem N, Tran AL, Duncan NR, Amster-Choder O, Golden SS, Cohen SE. J Biol Rhythms. 2023 Oct;38(5):447-460. doi: 10.1177/07487304231188761. Epub 2023 Jul 28. PMID: 37515350
  • Synchronization of the circadian clock to the environment tracked in real time. Fang M, Chavan AG, LiWang A, Golden SS. Proc Natl Acad Sci U S A. 2023 Mar 28;120(13):e2221453120. doi: 10.1073/pnas.2221453120. Epub 2023 Mar 20. PMID: 36940340
  • Cell specialization in cyanobacterial biofilm development revealed by expression of a cell-surface and extracellular matrix protein. Frenkel A, Zecharia E, Gómez-Pérez D, Sendersky E, Yegorov Y, Jacob A, Benichou JIC, Stierhof YD, Parnasa R, Golden SS, Kemen E, Schwarz R. NPJ Biofilms Microbiomes. 2023 Mar 2;9(1):10. doi: 10.1038/s41522-023-00376-6. PMID: 36864092
  • Glycogen metabolism is required for optimal cyanobacterial growth in the rapid light-dark cycle of low-Earth orbit. Bishé B, Golden SS, Golden JW. Life Sci Space Res (Amst). 2023 Feb;36:18-26. doi: 10.1016/j.lssr.2022.11.001. Epub 2022 Nov 4. PMID: 36682825
  • An unexpected role for leucyl aminopeptidase in UV tolerance revealed by a genome-wide fitness assessment in a model cyanobacterium. Weiss EL, Fang M, Taton A, Szubin R, Palsson BØ, Mitchell BG, Golden SS. Proc Natl Acad Sci U S A. 2022 Nov 8;119(45):e2211789119. doi: 10.1073/pnas.2211789119. Epub 2022 Nov 2. PMID: 36322730
  • Coupling of distant ATPase domains in the circadian clock protein KaiC. Swan JA, Sandate CR, Chavan AG, Freeberg AM, Etwaru D, Ernst DC, Palacios JG, Golden SS, LiWang A, Lander GC, Partch CL. Nat Struct Mol Biol. 2022 Aug;29(8):759-766. doi: 10.1038/s41594-022-00803-w. Epub 2022 Jul 21. PMID: 35864165
  • Transcriptomic and Phenomic Investigations Reveal Elements in Biofilm Repression and Formation in the Cyanobacterium Synechococcus elongatus PCC 7942. Simkovsky R, Parnasa R, Wang J, Nagar E, Zecharia E, Suban S, Yegorov Y, Veltman B, Sendersky E, Schwarz R, Golden SS. Front Microbiol. 2022 Jun 23;13:899150. doi: 10.3389/fmicb.2022.899150. eCollection 2022. PMID: 35814646
  • Comparative Genomics of Synechococcus elongatus Explains the Phenotypic Diversity of the Strains. Adomako M, Ernst D, Simkovsky R, Chao YY, Wang J, Fang M, Bouchier C, Lopez-Igual R, Mazel D, Gugger M, Golden SS. mBio. 2022 Jun 28;13(3):e0086222. doi: 10.1128/mbio.00862-22. Epub 2022 Apr 27. PMID: 35475644
  • Impairment of a cyanobacterial glycosyltransferase that modifies a pilin results in biofilm development. Suban S, Sendersky E, Golden SS, Schwarz R. Environ Microbiol Rep. 2022 Apr;14(2):218-229. doi: 10.1111/1758-2229.13050. Epub 2022 Feb 16. PMID: 35172394
  • 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

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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