Susan Golden

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]

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]

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]

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]