Congrats, Dr. Xinge Diana Zhang!

September 17, 2024

Diana has successfully defended her thesis! Title of Diana’s thesis: Techniques for High-Throughput Enzyme Evolution Using Droplet Microfluidics

Diana’s thesis: Techniques for High-Throughput Enzyme Evolution Using Droplet Microfluidics

Diana’s dissertation introduces groundbreaking advancements in enzyme evolution, a critical field that enhances enzymes used in industrial processes like biofuel production, pharmaceuticals, and fine chemicals. Natural enzymes, while versatile, often struggle with the stability and efficiency required for such applications, making directed evolution an essential strategy to optimize their performance.

Diana’s research focuses on high-throughput directed evolution, leveraging droplet microfluidics—a powerful tool that enables the rapid and efficient screening of millions of enzyme variants per day. By compartmentalizing individual enzyme variants into micrometer-sized droplets, this technology allows each droplet to function as a miniature reaction vessel, mimicking industrial conditions. This enables more precise screening for enzymes capable of performing effectively under harsh conditions, providing opportunities for enhanced stability and efficiency.

A major innovation in Diana’s work is the development of a platform that integrates nCas9 with a mutagenic polymerase to autonomously diversify genes, facilitating continuous evolution. This platform is combined with a custom lab-on-chip device to enable real-time screening and selection of optimized enzyme variants, significantly accelerating the evolutionary process. The continuous nature of this system allows for faster discovery of high-performing enzymes that can meet industrial needs, cutting down the time required for traditional iterative mutagenesis and screening cycles. This work is further detailed in the article Controlled Continuous Evolution of Enzymatic Activity Screened at Ultrahigh Throughput Using Drop-Based Microfluidics and Systems and Methods for Continuous Evolution of Enzymes.

In addition to advancing continuous evolution, Diana also developed a new method for generating more chemically diverse enzyme libraries. Using Random Saturation Mutagenesis (RSM), she created libraries that explore a broader range of mutations, overcoming the limitations of traditional methods that often introduce a narrow set of genetic variations. This enhanced diversity increases the likelihood of discovering novel enzyme variants with superior properties, offering significant advantages for industrial applications that require specialized enzymes for complex reactions.

Diana’s work offers potential applications in a variety of industries, including biotechnology, where optimized enzymes could improve the efficiency of biofuel production, and in pharmaceuticals, where engineered enzymes might lead to more cost-effective and efficient drug synthesis. Her research, highlighted by Nature Chemical Biology (https://www.nature.com/articles/s41589-023-01363-w), sets the stage for more rapid and precise enzyme discovery, with broad implications for solving real-world challenges in industrial biotechnology.