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Research interests |
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We have a broad range of research interests and some of the recent projects are listed below.1. Functional DNA (combinatorial selection)Sixty years ago, the famous structure of the DNA double helix was solved, bringing about the birth of modern molecular biology. Since then, DNA has been extensively studied as a genetic material. In the 1970s, solid-phase DNA synthesis was invented, allowing one to obtain arbitrary oligonucleotide sequences. In 1986, the invention of polymerase chain reaction (PCR) allowed an infinite number of DNA copies to be amplified from even a single molecule. These two techniques have made it possible to explore new functions of DNA. We are interested in using a combinatorial biology method called SELEX to isolate functional DNA sequences from a large random DNA library containing hundreds of trillions of sequences that carry chemical functions such as catalysis (e.g. DNAzymes) and molecular recognition (e.g. aptamers). A scheme of DNA selection is shown below.References: 2. Bio-nano interface (fundamental & applied research)Sixty years ago, the famous structure of the DNA double helix was solved, bringing about the birth of modern molecular biology. Since then, DNA has been extensively studied as a genetic material. In the 1970s, solid-phase DNA synthesis was invented, allowing one to obtain arbitrary oligonucleotide sequences. In 1986, the invention of polymerase chain reaction (PCR) allowed an infinite number of DNA copies to be amplified from even a single molecule. It is these two techniques that have made it possible to explore new functions of DNA. DNA has highly programmable structures that can be designed based on a simple base pairing rule. For example, a field called structural DNA nanotechnology has experienced rapid developments, manifested by the many published sophisticated 2D and 3D nanostructures.[1] Upon these structures, various nanoparticles have been deposited to offer other functions. Another interesting advancement was the discovery of DNA as a catalyst (catalytic DNA) and for molecular recognition (aptamer), making DNA a functional substitute for proteins. Compared to proteins, DNA is much more stable, easier to perform site-specific labeling, and easier for conjugation to various materials, popularizing DNA as the molecule of choice in constructing functional nano- and biomaterials.Nanomaterials.Nanomaterials are attractive because they possess unique size and distance-dependent physical properties. While particle size can be well controlled through chemical synthesis, the control of inter-particle distance with sub-nm precision and the organization of different types of particles remained difficult. DNA provides a unique solution to solving these problems. On the other hand, the molecular recognition property of DNA and DNA aptamers allows these nanomaterials to be used for biosensing and biomedical applications.[2,3] My lab is interested in exploring the biophysical interface between DNA and various nanomaterials to guide the design of better biosensors, biomaterials, and drug delivery systems. Fundamental understandings. Within a persistent length of ~50 nm, double-stranded DNA can be considered as a rigid rod with a diameter of just 2 nm. Each additional base pair contributes to a length increase of 0.34 nm. Therefore, sub-nm control of distance can be achieved using DNA. With the availability of a diverse range of attachment chemistry, DNA can be linked to almost all known nanomaterials. We are interested in studying the distance-dependent properties of various nanomaterials, including gold nanoparticles, liposomes, magnetic nanoparticles, quantum dots, and graphene using DNA as a linker. For example, Figure 1A shows the assembly of DNA-functionalized gold nanoparticles using a linker DNA with a subsequent color change from red to purple.[4] The same idea can be applied to the assembly of soft liposome nanoparticles (Figure 1B),[5] as well as gold-liposome hybrid (Figure 1C).[6] The inter-particle distance can be precisely controlled by changing the DNA sequence. Studying these systems can provide insights into the DNA-surface interaction as well as the coupling of physical events among the particles. |