Research Overview

The fascinating ‘RNA World’ hypothesis posits that RNA, a versatile and multifunctional macromolecule, serves as the impetus behind life’s abiogenesis, predating the emergence of DNA and protein. Beyond our general understandings of its genetic messenger functions encoded by A, U, G and C, RNA exhibits multifaceted functions, including self-replication, RNA/DNA cleavage and ligation, self-assembly, and more. The chemical structures of RNA are remarkably protean, extending beyond their canonical scaffolds, where diverse modifications can adorn their bases, sugars, and backbones. These RNAs with noncanonical structures are collectively referred to as Xeno nucleic acids (XNA).

Our lab is dedicated to leveraging cutting-edge innovations in nucleic acid chemistry to develop advanced tools for exploring fundamental biological questions, with a focus on RNA-protein interactions and self-assembly. These interactions and processes are pivotal to understanding various life processes, including gene regulation, protein synthesis, and cellular organization. XNAs, with their exceptional nuclease resistance and extended half-life in cells, emerge as a promising set of molecules for applications in these fields. Additionally, the modified sugar backbone confers its versatile chemical properties, distinct thermodynamics and the ability to form novel structures. By leveraging advances in synthetic nucleic acids, such as XNAs and modified RNAs, we plan to create new molecular probes and experimental systems. These tools will allow us to explore the structural dynamics and functional roles of RNA-protein complexes with unprecedented precision. Understanding these interactions is crucial not only for basic science but also for potential applications in drug discovery, synthetic biology, and the development of novel therapeutic strategies.

SELEX - In Vitro Evolution 

SELEX (Systematic Evolution of Ligands by Exponential enrichment), also referred to as in vitro selection or in vitro evolution, is a powerful technique widely used in molecular biology and biochemistry to enrich and identify nucleic acid sequences with specific and desired functions. This method involves the iterative selection of a pool of randomized RNA or DNA sequences against a target molecule, leading to the enrichment of those sequences that exhibit the extraordinary affinity or catalytic activity. Through multiple rounds of binding, selection, and amplification, SELEX can isolate aptamers or ribozymes. 

XNA/RNA Self Assembly/Synthetic Cells

We are motivated to reconstruct an artificial cell system to investigate genetic polymer self-assembly and self-replication. This artificial self-replication system will not only serve as a nanodevice for studying biochemical reactions but also allow us to explore fundamental principles of life’s origins by mimicking the processes that could have led to the emergence of living cells from non-living matter. By constructing and refining this system, we aim to gain insights into how genetic materials might autonomously organize, replicate, and evolve within a controlled environment. Our approach involves engineering synthetic cells that integrate novel genetic polymers, to test their capability for self-assembly and replication. This system will serve as a tool for understanding the mechanism underlying molecular interactions. and evolutionary dynamics in a simplified context. Furthermore, it will enable us to elucidate the chemical and physical conditions essential for the proper function of genetic polymers and provide a versatile nanosystem for various areas of biomedical research, including self-organization and molecular dynamics.