Research Interests
Our research lies in the interface of organic chemistry, molecular biology, and material sciences. We are using the research tools developed in these disciplines to advance new technologies and to answer intriguing scientific questions. Two representative projects are described.
"Bottom-up" Nanotechnology
The ultimate purpose of nanotechnology is miniaturization. According to Moore’s Law, the density of computer memory chips, manufactured through conventional photolithography methods, will reach its upper limit in a decade or so. Photolithography is one of the “top-down” approaches toward miniaturization (A), where a complete piece of material (e.g. a silicon wafer) is “carved” into small sections that accommodate electronic components. Although there is still room for innovation of “top-down” approaches, the consensus has been reached that revolutionary methods are needed for achieving further miniaturization into nanometer scales. As opposed to the “top-down” approaches, such methods are called “bottom-up” approaches.
In a typical "bottom-up" approach (B), small components for a device (e.g. a "nanochip") are prepared via synthetic chemistry. These molecular components should self-assemble according to certain rules to generate the final, complete structure. Synthetic chemistry has reached a certain degree of sophistication where most conceivable molecular structures can be synthesized. However, the rules for molecular self-assembly have been scarce. In this aspect, Nature shows unmatchable elegance. The complementary Watson-Crick DNA base-pairing rules (adenine pairs with thymine, guanine with cytidine) provide us a very powerful method for the production of “supramolecular” structures that have precise nanoscale features. Built upon such DNA nanotechnological accomplishments, our research will focus on how to load DNA-based supramolecular structures with useful molecular components with molecular resolution (C). Extensive synthetic chemistry development will be initiated to prepare functionalized nucleosides that can be easily incorporated into 2- or 3-dimentional DNA structures without interfering DNA base-pair complementarity. Another goal of this research is to engineer specific interactions, either optical or electrical, into small molecular components that will be installed in the DNA structures. To be able to prepare nanoscale suprastructures with molecular components precisely installed and to engineer specific interactions between those molecular components is a necessary step toward the creation of functional nanodevices for practical use.
Artificial Self-Replicating Systems
Self-replication, compartmentalization, and metabolism are three fundamental traits of life. Among them self-replication is the most relevant to the origin of life. The material basis for a self-replicating system has two key elements: the units that encode genetic information, and the way that such information is assembled. For example, DNA molecules, the material basis for genetic information propagation of natural organisms, have nucleobases as information-encoding units. These units are assembled through phophodiester bonds between individual nucleotides (D). But is there a general principle for constructing an artificial self-replicating system? Two rules have been proposed that are essential for self-replication: first, the rate for coupling information units (red in E) should be much slower than the rate of information recognition (blue) in order to preserve fidelity. Second, a genetic polymer needs to be a polyelectrolyte in order to minimize the interference of secondary structures to the genetic information recognition process. We are aiming to construct abiotic nucleic acid-based self-replicating systems based on these two principles. We will also explore the possibility of cross-communication between our systems and DNA or RNA. The existence of such interactions will have broad medical implications.
