| Leibniz Collaborative Excellence |
Epigenetic stability and plasticity of social environmental effects
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Dr. Alexandra Weyrich |
2018
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2023
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IZW
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Section C - Life Sciences
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Social status significantly affects Darwinian fitness by altering health, life history, and physiological trade-offs. Because social status is usually stable throughout life and a behaviourally transmitted trait, social inequalities persist within and across generations. Even so, the molecular mechanisms underlying these social effects are poorly understood. We hypothesize that DNA-methylation is a main epigenetic pathway through which an individual’s social environment regulates gene expression and hence physiological responses and life-history trade-offs. We predict that methylation patterns in individuals experiencing social stability will promote status-specific trade-offs. We further predict that when the social environment results in status changes as when high (low) born offspring are reared by a low (high) status surrogate mother, plasticity in methylation patterns should match the gene regulatory pathways, life-history trade-offs and fitness to the new social conditions. We test our hypothesis in the spotted hyena (Crocuta crocuta), a highly social mammal on which we accumulated detailed life-history data and biological samples from 30 years. To assess the impact of status-specific methylation patterns on health, we will measure faecal immunoglobulin, cytokine levels and eukaryome diversity, and will control for the possible confounding effect of gut microbiomes. By linking for the first time in a wild social mammal changes in social status to DNA-methylation, fitness and health, this project will shed light on gene pathways underpinning social inequalities, their plasticity, health consequences and potential implications for humans. External cooperation partners: Weizmann Institute of Sciences; University of Potsdam; McGill University
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| Leibniz Collaborative Excellence |
Epigenetic regulation of ImmuneAging: Heterochromatic DNA methylation as a regulator of T cell senescence
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Dr. Julia Polansky-Biskup |
2018
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2023
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DRFZ,
FLI,
FMP,
IZW
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Section C - Life Sciences
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Eines der größten Probleme des Alterns ist die reduzierte Wirksamkeit des Immunsystems, die zu verschiedensten altersbedingten Erkrankungen, einem erhöhten Infektionsrisiko und reduziertem Impferfolg führen kann. T-Lymphozyten sind essentiell am Alterungsprozess des Immunsystems beteiligt und zeigen dabei eine charakteristische chemische Veränderung (De-Methylierung) der DNA. Diese sogenannte "epigenetische" Veränderung wirken sich nicht auf die DNA-Sequenz, wohl aber auf die Struktur der DNA aus. In dem Projekt, das im Leibniz-Wettbewerb 2018 gefördert wurde, werden daher die Mechanismen und funktionellen Konsequenzen der DNA-De-Methylierung in T-Lymphozyten während des Alterungsprozesses des Immunsystems untersucht. Die Ergebnisse sollen nicht nur die internationale Grundlagenforschung voranbringen, sondern auch potentielle Biomarker für die Prävention und Behandlung der altersbedingten Immunschwäche identifizieren. Das Vorhaben führt somit das Leibniz-Thema „Gesundes Altern“ in exzellenter Weise weiter. Das interdisziplinäre Konsortium vereint die Kompetenz von vier Leibniz-Instituten und zwei universitären Partnern und verbindet zelluläre Grundlagenforschung mit klinischer Forschung. External cooperation partners: Charité Universitätsmedizin Berlin; Universität des Saarlandes
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| Leibniz Collaborative Excellence |
Using “signatures of selection” to decipher key mechanisms regulating fe/male fertility
|
Dr. Jennifer Schön |
2018
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2023
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FBN (former member institute),
IZW
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Section C - Life Sciences,
Section D - Mathematics, Natural Sciences, Engineering
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Curative therapies for infertility are rare, because the complex network of mechanisms determining reproductive success is largely unknown. To decipher parts of this network we use worldwide unique mouse lines created by long-term selection (180 generations) for the integrative fertility traits “increased litter size and weightâ€. These traits comprise core reproductive processes (i. a. gonad development, gamete recruitment, ovulation, fertilization and embryonic/fetal development). In the selection mouse lines, 45 years of litter size maximization have carved the causal alleles out of the genome as patterns of genetic invariance, the so-called “signatures of selectionâ€. We aim to detect these characteristic frequency patterns of alleles causal for the selected traits and identify the affected genes and pathways. We test if the genomic patterns resulting from selection for increased litter size (a primarily female trait) are also relevant for male reproductive physiology and performance. Finally, we employ comparative animal models to verify their general significance. With this project we will provide substantial new knowledge about the network of genes and pathways actually relevant for controlling central reproductive processes in mammals. External cooperation partners: Bundeshybridzuchtprogramm GmbH; Geolifes; Institut für Fortpflanzung landwirtschaftlicher Nutztiere; Universität Kiel
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