Abstract

The goal of this program is the development of new physical and chemical techniques to solve previously intractable problems in cell and molecular biology. More than half the effort will be devoted to the refinement of pulsed field gradient gel electrophoresis and the development of highly specific methods for cleaving DNA molecules. Together these techniques will allow rapid mapping of human genes, and molecular analysis of various chromosome rearrangements including genes and rearrangements linked to oncogenic transformation. Part of the program will focus on the topological properties of chromatin in tumor virus minichromosomes and in whole mammalian chromosomes. The object is to understand how chromatin structure and energetics change during gene expression and how the stiffness of DNA is used in normal and abnormal gene regulation. Another part of the program deals with the internalization of macromolecules by lymphocytes. One objective is to study how particular lymphocytes are able to internalize particular histocompatibility antigens. Another objective is to develop systems that exploit lymphocyte internalization to deliver photoactivatable drugs to malignant lymphoctyes. Finally, in two very speculative projects techniques will be developed to probe for the existence of RNA topoisomers and other techniques will be developed to produce fluorescently labeled proteins biosynthetically.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
5R35CA039782-07
Application #
3479022
Study Section
Special Emphasis Panel (SRC)
Project Start
1985-09-01
Project End
1992-08-31
Budget Start
1990-09-01
Budget End
1991-08-31
Support Year
7
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Lawrence Berkeley National Laboratory
Department
Type
Organized Research Units
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720

  Publications

Sano, T; Cantor, C R (2000) Streptavidin-containing chimeric proteins: design and production. Methods Enzymol 326:305-11
Sano, T; Vajda, S; Cantor, C R (1998) Genetic engineering of streptavidin, a versatile affinity tag. J Chromatogr B Biomed Sci Appl 715:85-91
Sano, T; Smith, C L; Cantor, C R (1997) Expression and purification of recombinant streptavidin-containing chimeric proteins. Methods Mol Biol 63:119-28
Sano, T; Smith, C L; Cantor, C R (1997) Deoxyribonucleic acids as unique markers in molecular detection. Genet Anal 14:37-40
Sano, T; Vajda, S; Reznik, G O et al. (1996) Molecular engineering of streptavidin. Ann N Y Acad Sci 799:383-90
Wang, D; Zhu, Y; Smith, C L (1995) A set of inter-Alu PCR markers for chromosome 21 generated from pulsed-field gel-fractionated NotI restriction fragments. Genomics 26:318-26
Sano, T; Pandori, M W; Chen, X et al. (1995) Recombinant core streptavidins. A minimum-sized core streptavidin has enhanced structural stability and higher accessibility to biotinylated macromolecules. J Biol Chem 270:28204-9
Gingrich, J C; Lowry, S R; Kuo, W L et al. (1993) Cloning and characterization of EagI YACs from human chromosome 21. Genomics 15:228-30
Sano, T; Smith, C L; Cantor, C R (1993) A streptavidin mutant containing a cysteine stretch that facilitates production of a variety of specific streptavidin conjugates. Biotechnology (N Y) 11:201-6
Zhu, Y; Cantor, C R; Smith, C L (1993) DNA sequence analysis of human chromosome 21 notI linking clones. Genomics 18:199-205

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