Team:SCUT-China
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Overview
According to the data from WHO, cardiovascular diseases are the main leading cause of death globally. Cyclic guanosine monophosphate (cGMP) is a critical second messenger molecule.It can transduce nitric-oxide (NO) and natriuretic-peptide-coupled signaling and remit the myocardial hypertrophy by relaxing the blood vessels. This summer, we tried to use synthetic biology to modify the cGMP metabolic pathway in a human cell line.We hope that our work would provide the proof of principle for future gene therapy.
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Soluble guanylate cyclase (sGC) is an enzyme that synthesize cGMP from GTP. We up-regulate sGC by overexpressing its α and β subunits in a mammalian cell line. However, elevated levels of cGMP leads to the feed-back expression of PDE5a, a cGMP-specific phosphodiesteras that degrades cGMP. Thus, we further modified the pathway by silencing the PDE5a. To achieve controllable up-regulation of cGMP level in the cell, we designed a hypoxia-inducible operon, HRE, as a switch to up regulate cGMP only in hypoxia situation.