Valerie Kay

BioE PhD Proposal Presentation 

Time and Date: 1:30 PM, Monday, November 21st, 2022

Location: ES&T L1120

Virtual Link: https://gatech.zoom.us/j/92013582451

Advisor: Corey Wilson, Ph.D. (Chemical and Biomolecular Engineering, Georgia Institute of Technology)

Committee Members:

John Blazeck, Ph.D. (Chemical and Biomolecular Engineering, Georgia Institute of Technology)

Julie Champion, Ph.D. (Chemical and Biomolecular Engineering, Georgia Institute of Technology)

Yury Chernoff, Ph.D. (Biological Sciences, Georgia Institute of Technology)

Brian Hammer, Ph.D. (Biological Sciences, Georgia Institute of Technology)

Engineering Transcriptional Programming to Develop Complete Decision Making and Memory in a Yeast Chassis Cell

Synthetic biology is a multidisciplinary approach to engineering new biological parts for beneficial purposes, such as developing complex genetic circuits. Transcription factors (TFs), which regulate transcription of targeted genes, are proficient at building these circuits. While transcriptional programming has been developed in prokaryotic chasses, there is growing interest in expanding these systems into higher-order eukaryotic cells, especially in the model yeast S. cerevisiae chassis. These cells have advantageous protein production and secretion capabilities, making them valuable for recombinant protein expression in biomanufacturing and for application as living therapeutics. Therefore, a modular set of TFs will be engineered for function in S. cerevisiae and used to build transcriptional programming, conferring this chassis with complete decision-making capabilities. Additionally, recombinase enzymes regulated by transcriptional programming will be used to build memory circuits that will enable the cells to permanently store decisions through inheritable changes in their genetics. To optimize these circuits, design rules for engineering allosteric communication of TFs de novo must be developed. Therefore, the allosteric pathways of LacI anti-repressors will be mapped using deep-mutational scanning. By building and optimizing genetic circuits, complete decision making and memory systems will be built in S. cerevisiae, conferring complete intelligence to this higher-order eukaryotic chassis.