This initiative supports fundamentally new approaches in molecular sciences to drive new directions in biotechnology, a critical and emerging technology of the 21st century. This is the fourth year of a campaign targeting broad themes to be pursued through collaborative high risk/high reward projects. This MFB solicitation calls for creative, cross-disciplinary research and technology development proposals to accelerate understanding of RNA function in complex biological systems and to harness RNA research to advance biotechnology. The funding opportunity will be coordinated by the National Science Foundation together with the National Institutes of Health, National Human Genome Research Institute (NHGRI). The focus on RNA science advances (1)Biotechnology innovation for a sustainable, safe and secure American bioeconomy; (2) theNSF 2022-2026 Strategic Planto create new knowledge and benefit society by translating knowledge into solutions; (3) theNHGRI 2020 Strategic Visionfor improving human health at the Forefront of Genomics; and aligns with (4) theNASEM Reportcalling for deeper understanding of RNA modifications and their role in biological processes. Award sizes must not exceed $1,500,000 intotalcosts(direct and indirect)for the entire projectand a duration of upto 3 years.The project budget and duration must be commensurate with the scale and scope of the research.