Essay Constructing Complex Synthetic Gene Circuits

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Regulation of any biological phenotype is a complex and tuned phenomenon (Weng et al, 1999). Biological systems face frequent change in the environment, both at intrinsic and extrinsic levels. These systems have evolved themselves to integrate these fluctuations and take an appropriate decision (Helikar et al, 2008). Classical genetics and DNA sequencing have provided a lot of information about different types of genes and their functions, but how do these genes interact and integrate environmental signals to encode different phenotypic responses, is not clearly understood. Emergence of synthetic biology has enabled biologists to characterize these genetic components in isolation and predict the behavior of complex networks. Synthetic…show more content…
Each repeat comprised of 33 to 34 amino acids. Different repeats vary mostly at position 12 and 13. Amino acids present at these two positions are called repeat variable di-residues (RVDs). Each RVD has preference for a nucleotide. Repeats are modular and can be assembled in required way to bind with any target DNA sequence (Gaber et al, 2014; Meckler et al, 2013). TALEs are thus a powerful and modular tool, which can be engineered to target any DNA sequence. Riboswitches are non-protein coding regulatory RNA, present in 5´ untranslated (UTR) region of mRNA, that upon binding with small molecules or peptides undergo conformational changes to control gene expression at translational level. Riboswitches are conceptually comprised of two parts (i) ligand specific aptamer domain, and (ii) expression platform, which undergoes structural changes in response to the changes in the aptamer (Winkler & Breaker, 2005). Ligand driven conformational change regulates translation either by sequestering ribosome binding site or by releasing it (Caron et al, 2012). Engineered riboswitches have been reported to be modular and work in dose dependent manner (Ceres et al, 2013; Dixon et al, 2010). Modular nature of Riboswitch and TALE encouraged us to design a novel set of regulatory systems, RiboTALEs, which have multidimensional input control, like natural complex gene circuits, target specificity, and shall have ability of scale-up to virtually control
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