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As for project design, we proposed to utilize small molecule metabolites screened from the Gut Microbial Metabolite Library to bind to the autoantibodies in brain of children with ASD by competitive inhibition, thus blocking autoantibody to neurons and alleviating neural damage to a certain extent in an immune-related subtype of ASD.
Firstly, we performed molecular docking analysis to screen the small molecule metabolites that can bind to the auto-antibodies and induce inactivation of antibody.
Secondly, we found bacteria capable of producing this metabolite in the gut microbiota repertoire. We induced this bacterium to produce this metabolite in large quantities by over-expressing some key enzymes in the production pathway to bind the autoantibody. Finally, we control the production of the engineered bacteria by suicide switch design to achieve the purpose of regulation.
In this project, from the perspective of small molecule blocking antibodies,we innovatively utilize small molecule metabolites from the Gut Microbial Metabolite Library and designed a certain amount of the selected intestinal metabolites through synthetic biology, which provides a new therapeutic target for the treatment of ASD.
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