Over the past 3.5 billion years, evolution has produced a vast diversity of proteins with distinct sequences, structures, and functions. Advances in high-throughput sequencing have led to the accumulation of extensive sequence data, and tools such as AlphaFold and ESMFold now enable accurate structure prediction for these rapidly expanding datasets. However, functional data that link sequence, structure, and function remain limited. To bridge this gap, we have developed various high-throughput techniques, from data mining to the generation of gene pools, to high-throughput genotyping and phenotyping. When integrated with artificial intelligence, these large-scale datasets enable not only the analysis of past evolutionary events but also the simulation of future evolutionary trajectories. This virtual and hybrid approach significantly enhances our ability to explore protein sequence and structure spaces, facilitating the discovery and design of proteins with novel properties and functions.

Our research encompasses a diverse range of protein systems, including random sequence libraries, fluorescent proteins, and enzymes—from small-molecule catalysts to genome-editing enzymes.

Our research mainly focuses on the following two principal areas:

I. Protein evolution

Current interests in the lab include but are not limited to: (a) deciphering protein fitness landscapes and studying their effects on protein evolution; (b) how foldability and stability affect protein evolvability; (c) how physical environments affect protein evolution; (d) how genetic code reduction and expansion affect protein evolution; (e) how functional proteins evolve from random protein sequences; (f) whether and how proteins evolve to harness quantum mechanics to perform their functions.

II. Protein engineering

Understanding protein evolution enables us to develop new strategies to engineer robust proteins that can meet industry requirements and serve as building blocks for synthetic biology. Specifically, our main focus lies on the following research directions: (a) developing robust enzymes/biological parts; (b) developing proteins with new or enhanced properties through genetic code expansion and post-translational modification; (c) developing extremophilic enzymes to meet some special industry requirements; (d) developing enzymes for non-aqueous catalysis.

We invite talented researchers with a passion for synthetic biology, molecular evolution, bioinformatics, computational modeling, and artificial intelligence to join us!