We propose to carry out a rapid genome-wide search for new mitogens and survival factors for stem and precursor cells of CNS, potentially doubling or more the number of known CNS mitogenic and survival factors over the course of two years. To do this, a novel protein expression technology, called Random Activation of Gene Expression (RAGE), will be used. RAGE libraries produced using genomic libraries carried in bacterial artificial chromosomes offer a number of advantages over conventional expression methodologies, including high-level expression without the need for full-length cDNAs. RAGE libraries produced in BAC libraries should allow the majority of secreted factors to be expressed and interrogated in the proposed research program. In addition to potential direct medical and therapeutic benefits, the discovery of new proteins with activities in promoting cell survival and division has considerable benefits on biological research in general. Even the limited number of growth factors available has provided a central foundation for the nascent field of stem cell biology in the CNS. Identifying proteins that further enable regulation of these populations will provide tools that may greatly extend our ability to achieve such important goals as repair of CNS damage.
