My third PhD paper has finally been published!
This project taught me not only how to design evolutionary trajectories, but also gave me the opportunity to experience the entire Design–Build–Test–Learn (DBTL) cycle from start to finish.
During the first half of my PhD, my research focused primarily on CRISPR-associated transposases: discovering new systems, improving their performance, and expanding their applications to additional microbial hosts. At the time, I thought I would continue along the path of genome editing tool development.
However, my advisor believed that I had not yet been exposed to what he considered the most powerful aspect of our lab: tackling challenging problems originating from industry, including some that industry itself had struggled to solve. Seeing that I still had some bandwidth, he assigned me a project aimed at understanding the mechanism of homotypic L-valine fermentation. Interestingly, this also gave me an opportunity to apply CRISPR-associated transposases during the Build phase of the DBTL cycle.
Through this work, I gained hands-on experience in metabolic engineering, adaptive laboratory evolution, metabolic flux analysis, enzyme activity characterization, next-generation sequencing analysis, and even the art of responding to reviewer comments (They considered the performance too good to be true). Today, nearly a year and a half into my postdoc at Berkeley, this study has finally been published in Nature Communications. (Ironically, shortly after the paper was accepted in principle, the journal was added to the list of journals that certain Chinese Academy of Sciences funding sources can no longer support.)
One of the key lessons from this project was surprisingly simple: when designing an anaerobic L-valine production strain, every excess metabolite needs an exit route. This insight has already been applied to the design of improved L-valine-producing strains.
Now I have returned to the field of genome engineering, working on microbiome editing. Hopefully, the technologies we are developing today will eventually find real-world applications as well.
On to the next paper!