title: Automated design of genetic toggle switches with predetermined bistability.
abstract: Synthetic biology aims to rationally construct biological devices with required functionalities. Methods that automate the design of genetic devices without post-hoc adjustment are therefore highly desired. Here we provide a method to predictably design genetic toggle switches with predetermined bistability. To accomplish this task, a biophysical model that links ribosome binding site (RBS) DNA sequence to toggle switch bistability was first developed by integrating a stochastic model with RBS design method. Then, to parametrize the model, a library of genetic toggle switch mutants was experimentally built, followed by establishing the equivalence between RBS DNA sequences and switch bistability. To test this equivalence, RBS nucleotide sequences for different specified bistabilities were in silico designed and experimentally verified. Results show that the deciphered equivalence is highly predictive for the toggle switch design with predetermined bistability. This method can be generalized to quantitative design of other probabilistic genetic devices in synthetic biology.
authors: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), School of Physics, Peking University, Beijng, 100871, China.
authors: Shuobing
authors: S
authors: Chen
authors: Haoqian
authors: H
authors: Zhang
authors: Handuo
authors: H
authors: Shi
authors: Weiyue
authors: W
authors: Ji
authors: Jingchen
authors: J
authors: Feng
authors: Yan
authors: Y
authors: Gong
authors: Zhenglin
authors: Z
authors: Yang
authors: Qi
authors: Q
authors: Ouyang
mesh_terms: D001665:Binding Sites / Q000235:genetics; D055592:Biophysical Phenomena; D003198:Computer Simulation; D017076:Computer-Aided Design; D004247:DNA / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D012270:Ribosomes / Q000378:metabolism; D058615:Synthetic Biology
chemical_list: D004247:DNA