National Institute on Aging
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Research Programs Intramural |
Human Genetics Section |
David Schlessinger, Ph.D., Chief Senior Investigator |
Overview: The program is designed to study embryonic and developmental events critical for the aging of specialized mammalian cells and concomitant aging-related phenomena. The program includes: |
1. Studies at the level of gene regulation in chromatin. Projects are designed to understand tissue- and developmentally-restricted expression of two genes, one that when mutated causes inherited premature ovarian failure (see below), and another that is placental-specific (PLAC1) and possibly involved in fetal well-being. Promoter and enhancer element functions are being analyzed in those instances. The regulatory processes involve features of chromatin; analyses of open and closed chromatin are projected for the genes recovered in chromatin form in artificial chromosomes in the Gene Recovery and Analysis Unit, headed by Ramaiah Nagaraja. |
2. Cohorts of genes involved in selected processes, using a "genome approach" to developmental phenomena. The approach starts from human inherited conditions and relevant embryological studies in mouse models (where sets of genes from embryonic stages can be easily assessed, and knockout technologies are available). Examples include: |
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The projected work will depend on the Gene Recovery and Analysis Unit, directed by Ramaiah Nagaraja, and collaborating groups. Related efforts are studying the genetic potential in the embryo-regulatory t-complex region of the mouse; and more directly relevant to human conditions, an extensive project is studying a favorably inter-related population in Sardinia to determine critical genes involved in aging-related traits, with the long-term aim of promoting patient benefit. |
Another group adapting new technology, the Image Informatics and Computational Biology Unit headed by Ilya Goldberg is helping to complete the range of necessary technology for functional genomics by developing quantitative visual assays. The unit is principal developer and co-founder of the Open Microscopy Environment (OME) project. OME is a software package and a set of standards for image informatics - the collection, maintenance, and analysis of biological images and associated data. The aim of this project is to standardize how image information is stored, extracted and transported between different software applications. In pilot work, current versions of OME have addressed applications of high-resolution imaging to track intracellular particles in real time, and screening applications involving hundreds of thousands of images. Currently, the group is continuing to develop relevant computational tools and information systems, and to apply them to two specific biological areas: determining the spatial distribution of differentially expressed gene products in pre-implantation mouse embryos, and visual screening of populations of the nematode C. elegans in which one gene is inactivated at a time across the genome. |
Investigators: |
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