{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/152489"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/152489","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"New Biological Pathways","abstract":"Through synthetic biology, our species is now learning to give biology instructions by using microscopic – often designed – biological components, allowing biology to conduct highly specialized forms of work previously unseen in nature. In this thesis, I propose and develop three new biological pathways which can perform three different categories of work i) information retrieval ii) information storage and iii) information editing. For information retrieval, I propose repurposing viral capsid proteins to perform non-destructive transcriptomic measurements. We demonstrate that this approach allows for live-cell transcriptomics, and we longitudinally measure the transcriptional responses of the same living human cells after stimulation with TNFa. For information storage, I propose and develop trans-splicing as a strategy to barcode the introduction of genetic elements en masse, and show that cell transcriptomes can be reliably barcoded for facile information storage. For information editing, I propose and develop a new RNA splicing machine – the splice editor – which can edit long stretches of mRNA sequences. I demonstrate that this CRISPR/Cas13 guided editor can perform exon replacement, which may one day lead to a new class of therapeutics. Altogether, this thesis showcases three new biological pathways, and demonstrates that living biological systems can be instructed to perform various kinds of complex, biological work.","abstract_html":"Through synthetic biology, our species is now learning to give biology instructions by using microscopic – often designed – biological components, allowing biology to conduct highly specialized forms of work previously unseen in nature. In this thesis, I propose and develop three new biological pathways which can perform three different categories of work i) information retrieval ii) information storage and iii) information editing. For information retrieval, I propose repurposing viral capsid proteins to perform non-destructive transcriptomic measurements. We demonstrate that this approach allows for live-cell transcriptomics, and we longitudinally measure the transcriptional responses of the same living human cells after stimulation with TNFa. For information storage, I propose and develop trans-splicing as a strategy to barcode the introduction of genetic elements en masse, and show that cell transcriptomes can be reliably barcoded for facile information storage. For information editing, I propose and develop a new RNA splicing machine – the splice editor – which can edit long stretches of mRNA sequences. I demonstrate that this CRISPR/Cas13 guided editor can perform exon replacement, which may one day lead to a new class of therapeutics. Altogether, this thesis showcases three new biological pathways, and demonstrates that living biological systems can be instructed to perform various kinds of complex, biological work.","abstract_has_math":false,"creators":["Borrajo, Jacob"],"institution":"Massachusetts Institute of Technology","degree_name":"Doctoral","degree_level":null,"degree_discipline":null,"degree_department":"Massachusetts Institute of Technology. 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I demonstrate that this CRISPR/Cas13 guided editor can perform exon replacement, which may one day lead to a new class of therapeutics. Altogether, this thesis showcases three new biological pathways, and demonstrates that living biological systems can be instructed to perform various kinds of complex, biological work."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph.D."]},{"key":"dc:title","label":"Title","values":["New Biological Pathways"]}]}],"canonical_facts":{"dc:contributor.advisor":["Blainey, Paul"],"dc:contributor.department":["Massachusetts Institute of Technology. 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For information storage, I propose and develop trans-splicing as a strategy to barcode the introduction of genetic elements en masse, and show that cell transcriptomes can be reliably barcoded for facile information storage. For information editing, I propose and develop a new RNA splicing machine – the splice editor – which can edit long stretches of mRNA sequences. I demonstrate that this CRISPR/Cas13 guided editor can perform exon replacement, which may one day lead to a new class of therapeutics. 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