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Title: Genes and gene expression: Localization, damage and control: A multilevel and inter-disciplinary study

Technical Report ·
DOI:https://doi.org/10.2172/6621658· OSTI ID:6621658

The main objectives of this Program Project is to develop strategy and technology for the study of gene structure, organization and function in a multi-disciplinary, highly coordinated manner. In Project I, Molecular Cytology, the establishment of all instrumentation for the computerized microscopic imaging system (CMIS) has been completed with the software in place, including measurement of the third dimension (along the Z-axis). The technique is now at hand to measure single copy DNA in the nucleus, single copy mRNA in the cell, and finally, we are in the process of developing mathematical approaches for the analysis of the relative spatial 3-D relationship among the chromosomes and the individual genes in the interphasal nucleus. Also, we have a sensitive and reliable method for measuring single-stranded DNA breaks which will be useful for the determination of damage to DNA caused by ionizing radiation. In Project II, the mapping of restriction fragments by 2-D enzymatic and electrophoretic analysis has been perfected for application. In Project III, a major finding is that the binding constant and effectiveness of antisense oligonucleotide analogues, Matagen, can be significantly improved by substituting 2{prime}-O-methylribos methylphosphonate backbones for the current 2{prime}-deoxyribomethylphosphonate backbones. 15 refs., 10 figs., 2 tabs.

Research Organization:
Johns Hopkins Univ., Baltimore, MD (United States)
Sponsoring Organization:
DOE/ER
DOE Contract Number:
FG02-88ER60636
OSTI ID:
6621658
Report Number(s):
DOE/ER/60636-3; ON: DE91000880
Country of Publication:
United States
Language:
English