The primary focus of work in the Molecular Genetics Section continues to be on growth regulation in mammalian cells. The investigation of growth inhibitory activity detected in a DNA-mediated gene transfer system is emphasized within this framework. Molecular cloning of growth inhibitory sequences is being pursued by analysis of a cosmid library derived from WI38 human embryo fibroblast genomic DNA. A single candidate cosmid clone exhibiting high growth inhibitory function has been identified. It contains sequences that hybridize under stringent conditions to a small transcript tentatively identified as 7SL RNA. Interestingly, this transcript is present in higher levels in WI3 fibroblasts, as well as in HeLa cells transfected with WI38 DNA sequences and selected in the growth inhibition assay, than in parental HeLa cells. To more effectively investigate the action(s) of these growth inhibitory sequences and those of growth stimulatory genes, we have developed a new magnetic affinity cell sorting method. Applications of this method, in particular for the introduction of growth inhibitory and/or growth stimulatory genes, the anti-sense complements of these genes, or regulatory sequences flanking these genes, are being explored.
