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Research

Image depicting the interconnectedness of the molecular processes in the cell. RNA and proteins cross-catalyze each other's synthesis in a network of complex reactions.
Figure generated with Biorender

The main directions of our research are:

(1) in vitro reconstruction of the transcription and translation apparatuses.

(2) minimization of the in vitro protein decoding apparatus.

(3) coupling energy regeneration to in vitro growth and replication.

Simplified schematic depicting the catalytic network of DNA, RNA, and proteins

1. Self-Replicating Transcription and Translation Apparatuses

The goal of this research area is to better understand how factors required for replication, transcription, and translation work in synergy to enable ensemble autocatalysis in living systems.

We will engineer cell-free gene circuits expressing these factors and study their populational persistence, evolvability, and variability.

Simplified schematic depicting the catalytic network of DNA, RNA, and proteins in interpreting the genetic code

2. Self-Replicating Minimal Genetic Decoding System

We will engineer and study cell-free self-replicating gene circuits expressing factors for genetic decoding (tRNAs and amino acyl-tRNA synthetases). tRNA will be co-evolved with corresponding aminoacyl tRNA synthetases toward reduced or removed reliance on modification enzymes, and thus towards minimization of the genetic code apparatus.

Simplified schematic depicting the catalytic network of DNA, RNA, and proteins in regenerating energy

3. Energy Regeneration

To better understand how energy regeneration is coupled to a living system’s growth and reproduction, gene circuits expressing factors for energy regeneration systems (e.g. components of ATP synthase) will be engineered. We will study their persistence, evolvability, and variability.