Bioconjugation
Our research in bioconjugation focuses on developing precise and modular strategies to connect biomolecules with synthetic chemical entities. We are particularly interested in site-specific protein modification enabled by genetic code expansion (GCE), which allows the incorporation of noncanonical amino acids (ncAAs) bearing unique chemical handles into proteins in living cells.
By introducing these ncAAs at defined positions, we explore bioorthogonal conjugation reactions such as click chemistry, together with protein splicing–based strategies, to enable controlled protein modification while preserving native structure and function. These strategies provide a modular framework for protein labeling, functionalization, and assembly.
We are also interested in extending these bioconjugation principles toward therapeutic and diagnostic applications such as antibody based conjugates. Although this direction is still at an early stage, our ongoing work explores how ncAA encoded chemical handles and modular protein ligation strategies could enable more homogeneous and precisely defined bioconjugates.
Sensors and Bioactuators
We develop genetically encoded chemical sensors and bioactuators that enable precise control of protein function in living systems using exogenous chemical inputs. Our work focuses on chemical signals that are orthogonal to endogenous cellular pathways, allowing selective and predictable regulation of biological activity.
A representative example is a fluoride activated protein control system based on genetic code expansion. In this system, a chemically caged tyrosine analogue is
incorporated into proteins at defined positions. Upon exposure to fluoride ions, the protecting group is removed and the native tyrosine residue is regenerated, switching protein function from an inactive to an active state. This approach has been demonstrated in both bacterial and mammalian cells using fluorescent proteins and enzymes.
More broadly, we view these systems as bioactuators that actively modulate protein activity, localization, or interactions in time and space. Our long term goal is to establish chemigenetic platforms that connect small molecule inputs to programmable biological outputs for applications in synthetic biology and cell engineering.
Directed Evolution
Our research in directed evolution focuses on expanding protein function beyond the limitations of natural amino acids. By combining genetic code expansion with evolutionary selection, we explore strategies to access protein activities and
molecular recognition modes that are difficult to achieve using the canonical amino acid repertoire.
Rather than relying solely on rational design, we are interested in evolutionary approaches that allow proteins to adapt to new chemical functionalities. In this context, we investigate general concepts for improving the efficiency and scope of directed evolution, without being restricted to a single implementation or system.
These approaches are applied to enzymes, interaction modules, and synthetic protein components, with an emphasis on discovering functional behaviors that emerge through selection. Our long term goal is to develop broadly applicable directed evolution frameworks that interface with chemical biology and synthetic biology.
Chemically Induced Dimerization
Our work on chemically induced dimerization focuses on creating artificial protein interaction modules that assemble conditionally in response to small molecules. By combining concepts from chemically induced dimerization with ncAA incorporation and protein engineering, we design interaction systems that are specific, tunable, and orthogonal to native cellular networks.
These systems can be applied to regulate a wide range of biological processes, including enzymatic activation, transcriptional control, and protein splicing. In particular, we are interested in coupling small molecule dependent dimerization with modular protein architectures to enable controllable assembly of functional protein complexes.
Rather than treating chemically induced dimerization modules as isolated tools, we aim to integrate them with bioconjugation, sensing and bioactuation, and directed evolution. Through this integrated perspective, our goal is to establish programmable chemical biological interfaces that enable precise control of cellular behavior.