Dissecting epigenetic signatures and cellular plasticity of Drosophila blood cells

剖析果蝇血细胞的表观遗传特征和细胞可塑性

• 批准号: 471670390
• 负责人: Professor Dr. Sven Bogdan
• 金额: --
• 依托单位: Institut für Molekularbiologie und Tumorforschung (IMT)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/471670390?language=en
• 关键词: Dissecting; epigenetic; signatures; cellular; plasticity

Physiological and pathological stimuli can induce cells to change their identity, a process referred to as transdifferentiation. We will use Drosophila blood cells as a model to dissect the molecular mechanisms underlying transdifferentiation. Larvae respond to insults such as wasp infection by a change of plasmatocyte into lamellocyte identity. Remarkably, lamellocytes appear after only eight hours. This rapid transdifferentiation involves dramatic changes to cell morphology and function: whereas plasmatocytes are small, multi-purpose macrophage-like cells, lamellocytes are highly specialized, giant cells that seek out wasp eggs and contribute to their destruction. Our preliminary results implicate three novel players in the regulation of lamellocyte formation: the transcriptional regulator U-shaped (Ush), the Nucleosome Remodeling and Deacetylation (NuRD) complex and Casein Kinase 2 (CK2). In this project we will test the hypothesis that CK2-mediated phosphorylation of NuRD facilitates swift alterations of the epigenome and transcriptome allowing the rapid expression of proteins that drive dramatic changes of cell morphology, motility and phagocytotic activity. Towards this end, we will combine our complementary expertise in genome-wide studies, proteomic approaches, genetics and high-resolution microscopy. The strong evolutionary conservation of factors and mechanisms between Drosophila and man shaping the innate cellular immune system gives our study a broad biomedical relevance.

生理和病理刺激可以诱导细胞改变其身份，这一过程称为转分化。我们将使用果蝇血细胞作为模型来剖析转分化的分子机制。幼虫通过将浆细胞转变为片状细胞身份来应对黄蜂感染等侮辱。值得注意的是，仅八小时后就出现了片状细胞。这种快速转分化涉及细胞形态和功能的巨大变化：浆细胞是小型、多用途的巨噬细胞样细胞，而片状细胞是高度特化的巨细胞，它们寻找黄蜂卵并促进其破坏。我们的初步结果表明板层细胞形成调节中的三个新参与者：转录调节因子 U 形 (Ush)、核小体重塑和脱乙酰化 (NuRD) 复合物以及酪蛋白激酶 2 (CK2)。在这个项目中，我们将测试这样的假设：CK2 介导的 NuRD 磷酸化促进表观基因组和转录组的快速改变，从而允许蛋白质的快速表达，从而驱动细胞形态、运动和吞噬活性的巨大变化。为此，我们将结合我们在全基因组研究、蛋白质组学方法、遗传学和高分辨率显微镜方面的互补专业知识。果蝇和人类塑造先天细胞免疫系统的因素和机制在进化上具有很强的保守性，这使我们的研究具有广泛的生物医学相关性。