The advent and widespread application of the recombinant DNA methodology during the past twelve years has greatly extended our understanding of the molecular basis of heredity. More significantly, the emergence of a new molecular paradigm - reverse genetics, which relies on the ability to specifically modify the structure of genes in vitro and to test their biological properties, has revolutionized the experimental approaches in molecular genetics. The ability to construct minichromosomes with novel arrangements of genetic elements also provides vectors for the isolation of genes as well as substrates for the analysis of specific genetic reactions. Our proposal, which applies this approach to explore the basic mechanisms of gene regulation in the establishment of immune responsiveness and of genetic recombination, aims (1) identify the factors and mechanisms that limit the epression of antibody genes to only lymphoid cells; (2) isolate and characterize the human gene whose dysfunction is responsible for galactosemia; (3) understand the mechanisms responsible for non- homologous, homologous and non-reciprocal modes of genetic recombination, especially those which permit the rejoining of broken DNA; (4) develop genetic approaches to effect a replacement or repair of chromosomal DNA sequences; (5) developing vectors which can deliver genes to only specific types of cells. It is anticipated that the information we develop will advance our unerstanding of the molecular basis of disease and provide novel approaches to their prevention, treatment and cure.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM013235-24
Application #
3484144
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1975-09-01
Project End
1992-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
24
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Stuhlmann, H; Berg, P (1992) Homologous recombination of copackaged retrovirus RNAs during reverse transcription. J Virol 66:2378-88
Jasin, M; Page, K A; Littman, D R (1991) Glycosylphosphatidylinositol-anchored CD4/Thy-1 chimeric molecules serve as human immunodeficiency virus receptors in human, but not mouse, cells and are modulated by gangliosides. J Virol 65:440-4
Pontius, B W; Berg, P (1991) Rapid renaturation of complementary DNA strands mediated by cationic detergents: a role for high-probability binding domains in enhancing the kinetics of molecular assembly processes. Proc Natl Acad Sci U S A 88:8237-41
Stuhlmann, H; Dieckmann, M; Berg, P (1990) Transduction of cellular neo mRNA by retrovirus-mediated recombination. J Virol 64:5783-96
Jasin, M; Elledge, S J; Davis, R W et al. (1990) Gene targeting at the human CD4 locus by epitope addition. Genes Dev 4:157-66
Pontius, B W; Berg, P (1990) Renaturation of complementary DNA strands mediated by purified mammalian heterogeneous nuclear ribonucleoprotein A1 protein: implications for a mechanism for rapid molecular assembly. Proc Natl Acad Sci U S A 87:8403-7
Margolskee, R F; Kavathas, P; Berg, P (1988) Epstein-Barr virus shuttle vector for stable episomal replication of cDNA expression libraries in human cells. Mol Cell Biol 8:2837-47
Buchman, A R; Berg, P (1988) Comparison of intron-dependent and intron-independent gene expression. Mol Cell Biol 8:4395-405
Reichardt, J K; Berg, P (1988) Conservation of short patches of amino acid sequence amongst proteins with a common function but evolutionarily distinct origins: implications for cloning genes and for structure-function analysis. Nucleic Acids Res 16:9017-26
Reichardt, J K; Berg, P (1988) Cloning and characterization of a cDNA encoding human galactose-1-phosphate uridyl transferase. Mol Biol Med 5:107-22

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