Jeffrey Simon - US grants
Affiliations: | University of Minnesota, Twin Cities, Minneapolis, MN |
Area:
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The funding information displayed below comes from the NIH Research Portfolio Online Reporting Tools and the NSF Award Database.The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
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High-probability grants
According to our matching algorithm, Jeffrey Simon is the likely recipient of the following grants.| Years | Recipients | Code | Title / Keywords | Matching score |
|---|---|---|---|---|
| 1993 — 1997 | Simon, Jeffrey | N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Transcriptional Repression by Polycomb Group Products in Drosophila @ University of Minnesota-Twin Cities 9304936 Simon The aim of this research is to understand how stable states of gene expression are maintained during development. Molecular genetic and biochemical methods will be used to study proteins that control transcription of homeotic genes in Drosophila melanogaster. The homeotic genes determine the identities of segments in the fly. Expression of the homeotic genes, in restricted positions along the anterior-posterior axis, is needed throughout embryonic, larval and pupal development. Segmentation gene products activate the homeotic genes in restricted positions in 2-hr old embryos, but they decay by about 4 hrs. The Polycomb group (PcG) products then maintain restricted homeotic gene expression throughout subsequent development. The PcG products repress transcription of homeotic genes in positions where they are not normally expressed. Current models suggest that the PcG products recognize homeotic genes that are repressed initially and they maintain this repression by assembling stable protein-DNA complexes in the chromatin at these loci. This research will investigate the individual roles of PcG repressor proteins. Much of the work will focus on the extra sex combs (esc) protein, which may play a short-term role in assembling or guiding other PcG proteins that act as stable repressors. A major objective of this work is to determine the biochemical roles of esc protein. This research will test if and how esc protein interacts with other PcG proteins and when during development these interactions occur. Antibody to esc protein will be produced and the times and places of esc protein accumulation will be determined by protein blotting and whole mount staining of embryos. Immune precipitations will be performed to test for esc association with other PcG proteins and to check for esc protein binding to DNA. Site-specific mutagenesis, coupled with germline transformation, will test a protein domain found in esc, and the yeast repressor TUP1, fo r a role in protein-protein contact. An "interaction-trap" screen will be performed, using yeast cells, to identify fly proteins that associate with esc protein. Finally, a genetic screen will be performed in flies to identify novel PcG genes. The screen will use P elements as transposon mutagens. Transposon- tagged PcG genes will be cloned by PCR methods and their molecular analysis will be initiated. Once a program of gene expression is established in cells of a developing embryo or tissue, it is important that inappropriate genes are stably repressed. Repression of homeotic genes by PcG proteins provides a model for how a determined state of gene expression is maintained during development. By investigating how PcG products work, we will learn how developmental decisions, once made, are stabilized at the molecular level. Similar molecular mechanisms may be employed during development in a variety of organisms. Indeed, there are similarities in sequence, organization and function between fly homeotic genes and similar genes found in organisms as diverse as worms and mice. *** |
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| 1996 — 2017 | Simon, Jeffrey A | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Transcriptional Repression by Polycomb Group Products @ University of Minnesota Twin Cities DESCRIPTION (provided by applicant): The aim of this research is to understand how stable states of gene expression are maintained during development. Molecular, genetic and biochemical methods will be used to study chromatin proteins that control transcription of homeotic (Hox) genes in Drosophila melanogaster. Hox genes determine fly segment identities and their selective expression is needed throughout development. Segmentation gene products control initial patterns of Hox expression in 2-hour-old embryos, but they decay by about 4 hours. The Polycomb group (PcG) proteins are transcriptional repressors that then maintain Hox expression patterns during the rest of development. Current models suggest repression is maintained through covalent histone modification and stable association of PcG protein complexes in the local chromatin. This research will investigate molecular roles of PcG complexes and their subunits. Two biochemically separable PcG complexes have been purified; the ESC-E(Z) complex contains the PcG proteins Extra sex combs (ESC), Enhancer of zeste [E(Z)] and Suppressor of zeste-12 [SU(Z)12]. This complex has an enzyme activity that methylates histones. The other complex, called PRC1, contains Polycomb (PC), Polyhomeotic (PH), Posterior sex combs (PSC) and Sex comb extra (SCE). This work will address mechanisms that regulate the ESC-E(Z) complex and define roles of individual subunits. Another goal is to determine if and how the Sex comb on midleg (SCM) repressor works with PRCI. Additional studies will track PcG chromatin states during the cell cycle. The methods used will include protein purification, enzyme assays, site-directed mutagenesis, chromatin analyses, loss-of-function studies, transgene manipulating, protein interaction tests, and immunostaining of chromosomes. Every fly PcG repressor has homologs in mammals. These are functional homologs since PcG knockouts produce Hox defects in mouse embryos that parallel defects in fly PcG mutants. Human PcG complexes resemble their fly counterparts in composition and activity. Thus, determination of PcG mechanisms in flies should yield insight about developmental controls in higher organisms. PcG repressors are implicated in lymphomagenesis and in normal hematopoiesis. The human homolog of E(Z) is implicated in disease progression of breast and prostate cancers. Knowledge about PcG mechanisms in flies may thus improve understanding of normal blood cell development and processes that underlie these human cancers. |
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