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.