This National Science Foundation (NSF) Mathematical and Physical Sciences (CFDA 47.049) project grant award of $1,500,000 supports research by Dr. Tamar Schlick of New York University and Dr. Alain Laederach of the University of North Carolina at Chapel Hill. The project aims to develop advanced computational tools to predict and control how viral protein synthesis is affected by programmed ribosomal frameshifting (PRF) - the mechanism by which viruses and human cells modify gene expression. Key activities include computationally predicting and experimentally testing how mutations to mRNA affect its 3D structure and frameshifting in prototype viral genomes. The goal is to reveal the structural and sequence requirements for frameshifting to facilitate the design of novel efficient frameshifting elements with potential applications to viral gene packaging and delivery. The project will provide interdisciplinary STEM training and public outreach. A sub-award to UNC-Chapel Hill supports SHAPE-MAP experiments and luciferase assays to assess frameshifting element function, which will be integrated with computational models from NYU.