Research at Nucleic Acid Chemistry and Engineering Unit
Nucleic acids such as DNA and RNA exhibit a wide range of biochemical functions including transfer of genetic information, regulation of gene expression, molecular recognition, and chemical catalysis. No other classes of molecules (e.g. proteins, polymers) exhibit such functional diversity. The objective of Nucleic Acid Chemistry and Engineering Unit is to harness the intrinsic functional versatility of natural and artificial nucleic acids to engineer nucleic acids with sophisticated functions.
Actual projects that postdocs and students work on largely depend on individual background and interests within the context of nucleic acid chemistry and engineering. For example, we currently have a variety of projects such as:
Applications of high-throughput sequencing to analyze and engineer nucleic acid enzymes.
Development and applications of riboswitches in mammalian cells, viruses, bacteria, and artificial cells.
Synthesis and applications of nonnatural nucleic acids.
New or improved methodologies and techniques play a key role in our ability to design nucleic acids with sophisticated functions. We have developed and will continue to develop new methods that significantly accelerate our ability to design and analyze functional nucleic acids. These methods are used, along with other available methods, for various applications.
For example, we are developing new methods to use high-throughput sequencing to quantitatively analyze tens of thousands of ribozyme and deoxyribozyme mutants which also enable us to engineer better riboswitches that control gene expression in living cells. We are also adapting microfluidic technology to rapidly engineer other types of nucleic acid devices.
Engineered nucleic acids, RNA in particular, can potentially be used within living cells to interact with the intracellular molecules and control living cells. Over the years, we have designed various RNA-based gene switches (riboswitches) that can regulate gene expression in bacteria and in mammalian cells in response to chemical signals. We are also interested in exploiting these synthetic RNA devices to other applications such as metabolic engineering, stem cell engineering, and gene therapy. Several collaboration projects are ongoing with industry and academic partners. For these types of projects, we look for researchers with diverse life sciences background who can generate ideas for new applications.
We are interested in designing simple and complex chemical systems composed of multiple nucleic acid components and modules. We recently designed an RNA biosensor circuit that amplifies a chemical signal and produces an optical signal (fluorescence). These synthetic chemical systems composed of nucleic acids not only challenge the limits of nucleic acid chemistry, but also serve as models for future biological applications.
We are also interested in using unnatural nucleic acids to expand the scope of nucleic acid-based chemical systems, developing novel aptamers for biological applications, developing novel small molecules to control nucleic acids, constructing artificial cells that encapsulate nucleic acid devices, etc. For these efforts, we welcome nucleic acid chemists with organic synthesis skills.
We have multiple formal and informal collaborations with groups within and outside OIST, including an industrial partner.