The laboratory of Sherman Weissman is using several approaches to obtain rapid overall analyses of gene expression in mammalian cells, taking advantage of the emerging sequence data. We have
developed improved methods of differential display of cDNA, of PCR, and of surveying sequence specific DNA binding proteins, and are working on several other methods to identify and survey levels of expression of cDNAs and proteins encoding interacting components, defined amino acid motifs, or defined types of post-transcriptional modificiations, as well as approaches for genome scanning for mutation detection including the mapping of genes contributing to complex phenotypes.We are studying genes of the human Major Histocompatibility Complex. In addition to known families of proteins encoded in the MHC, we have identified and are studying at least five new groups of proteins that appear to function specifically in the immune system.We are analyzing the patterns and regulation of gene expression in the hematopoietic system, testing new approaches on relatively familiar problems. In partcular, we are working on the mechanisms of developmental switching of globin genes in erythroid cells and on the responses to various activation signals in T cells and neutrophils, and on the process and mechanisms leading to selective subcellular distribution and stability of mRNAs. In the future we expect to extend our studies to the mechanisms of replication arrest consequent to checkpoint signalling and senescence of cells in culture.
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