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  • Thumbnail for Construction and characterization of a noise control system in human embryonic kidney cells (HEK293)
    Construction and characterization of a noise control system in human embryonic kidney cells (HEK293) by Wu, Qiu Chang

    Non-genetic cellular heterogeneity is often overlooked in the study of molecular biology. Population averaged measurements of clonal cell populations are made under the assumption that genetic homogeneity implies cellular homogeneity. On the contrary, such assumption discounts the vast variability that exists within a clonal cell population. When gene expression of individual genes is observed across a clonal population of mammalian cells, variation in expression of the same gene differ between cells. This phenomenon is defined as gene expression noise and has been shown to have a functional role in processes like cell fate decisions and viral latency reactivation. While many efforts have been made to measure gene expression noise, less is known about how to control noise. Here, we present our work towards controlling noise using a synthetic genetic circuit we call a noise rheostat. The circuit we built places two small-molecule inducible transcription systems linked in series, driving expression of a green fluorescent protein reporter gene. The inducible transcription system includes an abscisic acid inducible synthetic transcription factor with its cognate promoter and a doxycycline inducible transcription factor with its cognate promoter. By using two inducible transcription systems in series, we create lags in transcription of the terminal output and thus produce different noise levels. We performed transient transfections and characterized the system through dosage experiments using flow cytometry. The datasets analyzed demonstrate that gene expression noise is dialable while maintaining gene expression mean. These results offer a promising prototype for the first mammalian noise rheostat. We propose that this tool will be useful in the study of noise biology as it provides the ability to separate the control of gene expression mean from gene expression noise.