NSF Award
2317395
With support from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry, Professor Niles A. Pierce of the California Institute of Technology (Caltech) will develop new algorithms for nucleic acid analysis and design. Nucleic acids (DNA and RNA) orchestrate life by interacting within complex biological circuits to grow, regulate, and repair organisms. Over the coming decades, engineering of DNA and RNA within the emerging fields of molecular programming, nucleic acid nanotechnology, and synthetic biology are poised to generate transformative programmable molecular and cellular technologies addressing diverse challenges to science and society ranging from environmental monitoring and biosphere engineering to diagnosis and treatment, and from renewable energy to sustainable manufacturing. To support these engineering efforts, the Pierce Lab at Caltech is engaged in a multi-decade effort to develop NUPACK (Nucleic Acid Package), a growing software suite for analyzing and designing nucleic acid structures, devices, and systems. Here, they will expand NUPACK’s capabilities by pursuing three major goals. First, they aim to develop algorithms to enable simulation of functional nucleic acid systems with moving parts. Second, they will develop analysis and design algorithms that enable treatment of systems that contain mixed materials (e.g., both DNA and RNA, or both DNA and a synthetic nucleic acid analog such as LNA) that are critical to modern applications whether in living organisms, on the laboratory bench, or in the field. Third, they will endeavor to generalize the NUPACK cloud web app to enable users to efficiently leverage these unique computational tools for both research and education. <br/><br/>NUPACK is a growing software suite for the analysis and design of nucleic acid structures, devices, and systems serving the needs of researchers in the emerging disciplines of molecular programming, nucleic acid nanotechnology, synthetic biology, and across the life sciences. NUPACK algorithms are unique in treating complex and test tube ensembles containing arbitrary numbers of interacting strand species, providing crucial tools for capturing concentration effects essential to analyzing and designing the intermolecular interactions that are a hallmark of these fields. Here, the Pierce Lab at Caltech proposes to significantly expand NUPACK's capabilities by pursuing three major goals. First, to enable simulation of functional nucleic acid systems with moving parts, they will develop automated kinetic coarse-graining algorithms to enable kinetic analysis of complex and test tube ensembles. Second, to enable engineering of mixed-material systems (e.g., DNA/RNA or LNA/DNA) that are critical for modern applications in vitro, in situ, and in vivo, they will develop mixed-material models and algorithms for the analysis and design of complex and test tube ensembles. Third, they will generalize the NUPACK cloud web app to encompass these new capabilities, enabling researchers and students to efficiently leverage these unique tools with parallel execution in the scalable NUPACK hybrid cloud. These new analysis and design capabilities are expected to have broad scientific impact, contributing to the development of new molecular and cellular technologies that will ultimately have applications ranging from environmental monitoring and biosphere engineering to the development of nucleic acid therapeutics.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
