Simulation of gene regulatory elements for biosensing

Mallory Bates, Svetlana Harbough, Tarun Goswami
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Abstract

Gene regulatory studies are of significant importance in many scenarios such as mental illness. 21% of U.S adults experience mental illnesses including 1 in 4 active-duty military personnel. Mental health can be identified in the body by different biomarkers. These biomarkers potentially controlled by riboswitches, which are located in mRNA and switch “ON” or “OFF” depending on the concentration of a biomarker. In this research, a known riboswitch reengineered and its response in the presence of a biomarker investigated. We changed computationally PreQ1, a known riboswitch that has the smallest aptamer, and then experimentally tested against biomarkers, dehydroepiandrosterone-sulfate (DHEA-S), Serotonin, Cortisol, Dopamine, Epinephrine, and Norepinephrine. A total of 7 variant riboswitches were tested in this research, 4 created computationally discussed here and 3 experimentally not covered in this paper. The results from these variants showed that variants 1 and 2 had different responses to DHEA-S then the expected PreQ1 response. A dose response showed downward trend as DHEA-S concentration increased. In conclusion of this research, riboswitches can be re-engineered to have a different response to biomarkers at the same time keeping the same structure.
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生物传感基因调控元件的模拟
基因调控研究在许多情况下都具有重要意义,如精神疾病。21%的美国成年人患有精神疾病,包括四分之一的现役军人。心理健康可以通过不同的生物标记来识别。这些生物标记物可能受到核糖开关的控制,核糖开关位于mRNA中,根据生物标记物的浓度开关“开”或“关”。在这项研究中,一个已知的核糖开关重组和其反应在生物标志物的存在进行了研究。我们通过计算改变了PreQ1,一种已知的具有最小核酸适合体的核糖体开关,然后通过实验测试了生物标志物,脱氢表雄酮硫酸盐(DHEA-S),血清素,皮质醇,多巴胺,肾上腺素和去甲肾上腺素。本研究共测试了7个不同的核糖体开关,其中4个在计算中创建,3个在实验中未涉及。这些变异的结果表明,变异1和2对DHEA-S的反应与预期的PreQ1反应不同。随着DHEA-S浓度的升高,剂量效应呈下降趋势。在这项研究的结论中,核糖开关可以被重新设计,在保持相同结构的同时对生物标志物有不同的反应。
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