Title

Cross-kingdom Expression of Synthetic Genetic Elements Promotes the Discovery of a New Class of Nucleotide Analogs from the Human Microbiome

Date of Award

Fall 10-1-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Molecular, Cellular, and Developmental Biology

First Advisor

Isaacs, Farren

Abstract

The ability to mobilize functional genetic cargo into a versatile array of hosts is a defining challenge, as scientists increasingly reprogram diverse organisms as living therapeutics, for bioremediation, and as foundries for producing materials and molecules. However porting genetic material to diverse recipients is challenged by barriers to robust expression and mobilization. To address these challenges, we have developed an approach that integrates computer aided redesign of genetic sequences that are subsequently mobilized, expressed, and characterized cross-kingdom in diverse microbial hosts, including Gram negative and positive bacteria and yeast. Using the technology developed in this thesis, we were able to uncover a new class of bioactive nucleotide analogs from human microbiome. However, as with any technology, there remain numerous gaps that invite further study. In the discussions of Chapters 2, 3, and 6, which focus on technology, I discuss these deficiencies in detail, and offer my thoughts and ideas on future directions that can address them. The methods developed in this thesis will have broader impact on our ability to engineer nature in order to discover new biology, and design new functions.

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