description): This project examines the feasibility of using ribosome display methodology to select for novel RNA-binding domains (RBDs) that specifically bind to new RNA targets. If successful, it may become possible to engineer novel RBDs that can regulate gene expression and DNA replication in cell-free systems and in a wide variety of transgenic cells and organisms, and to use such proteins to study and manipulate cellular or viral control processes with a high degree of specificity and accuracy. This could in turn aid the development of new therapeutic applications. The project's risk revolves around two uncertainties: 1) the current translation/selection methods of ribosome display may not be adequate for the proposed application, and 2) some RNA-binding domains may require more than nine aminoacyl residues to determine target specificity. Initial results using the human U1A RBD1 as a starting template indicate feasibility, but many problems remained unsolved and may prove insurmountable.
