Rykowski 9507091 The overall objective of this work is to determine the complete 3-dimensional interphase chromosome structure of specific genes of Drosophila melanogaster at several critical times in development in diploid embryonic chromosomes. The parameters of the ultra-high resolution in situ hybridization (URISH) and computational optical microscopy and image analysis will be characterized followed by a characterization of cell by cell variation in transcription using the Notch gene. The effect of global structure on gene activity will also be determined. There will be on-going software development which should be of use in other studies as well as this work. %%% An integral part of gene regulation is the structure of the gene itself. Proteins associated with the chromosome on a constitutive basis act to modulate the action of transcription factors and replication machinery. Alterations in chromatin structure early in embryonic development can lead to the wholesale silencing of the genes. Clearly, the structure of interphase chromosomes is an active player in gene regulation. Using high resolution in situ hybridization and computational optical microscopy, the structures of the gene changes during development and as a result of cell cycle progression will be determined. ***
