Maternal organelle contribution to offspring germline health

项目摘要 细胞器参与稳态过程以改善细胞健康。然而，一些细胞器蛋白质， 索马可以存活数月，这使得它们在衰老过程中容易受到损伤。在生殖细胞中，配子 在它们将细胞器内容传递给下一代之前，可以被长时间地抑制。 因此，在生殖细胞中保留有损伤倾向的蛋白质将是一个问题，并挑战人类的能力。 将健康的物质代代相传。卵母细胞成熟后， 在受精过程中，某些母体产物被降解，从而在发育过程中启动母体向合子的转变。 胚胎，尽管很少有人知道母体来源的细胞器是如何被合子所取代的。 细胞器有趣的是，质量控制事件已被证明发生在单细胞生物体中， 不对称分裂以确保消除细胞器长寿命蛋白（LLP）。但无论 进行专门的细胞器质量控制，以去除发育中的后代中的母体来源的LLP， 这种过程如何在多细胞生物体中发生仍然知之甚少。通过分子 和遗传分析，这项研究提出的奖学金将调查如何母体细胞器输入 来自果蝇卵母细胞的基因会影响其后代的生殖系健康。首先，我将内生地标记好 特征化的LLP，以可视化合子蛋白池沿着母系衍生的长寿命蛋白池。 胚胎、幼虫和成年后代的蛋白质相同。通过区别标记母体和合子 池，我将比较蛋白质水平的后代生殖细胞，以评估是否有选择性地防止母体沉积 细胞器LLP可以跨代遗传。接下来，我将扰乱卵母细胞的健康， 受损的LLP有助于后代的生存能力。最后，我将确定其他长寿的蛋白质， 使用双正交氨基酸标记方法从母体细胞器中获得，并比较它们在 具有良好表征的LLP的子代种系。拟议中的实验将强调母性如何 衍生的LLP影响随后后代的生殖系中的细胞器功能。此外，这些研究将 了解细胞器的连续性如何在世代之间保持，旨在揭示专门的质量控制 生殖细胞中的通路。

Project Summary Organelles engage in homeostatic processes to improve cellular health. However, some organelle proteins in the soma can survive many months, making them susceptible to damage during aging. In the germline, gametes can be arrested for a prolonged period before they pass down their organelle content to the next generation. Having damage-prone proteins perdure in the germline would therefore be problematic and challenge the ability of germ cells to pass down healthy material from generation to generation. Upon oocyte maturation and fertilization, certain maternal products are degraded to initiate the maternal to zygotic transition in the developing embryo, though little is known how maternally derived organelles are turned over and replaced with zygotic organelles. Intriguingly, quality control events have been shown to take place in single cell organisms and during asymmetric divisions to ensure the elimination of organelle long-lived proteins (LLPs). However, whether specialized organelle quality control takes places to remove maternally derived LLPs in developing progeny, and how such a process would take place in a multi-cellular organism remains poorly understood. Through molecular and genetic analysis, the research proposed in this fellowship will investigate how maternal organelle input derived from Drosophila oocytes influences germline health of their offspring. First, I will endogenously tag well characterized LLPs to visualize the zygotic pool of proteins along with the maternally derived long-lived pool of the same protein across embryonic, larval and adult progeny. By differentially tagging the maternal and zygotic pool, I will compare protein levels in the progeny germline to assess if it selectively prevents maternally deposited organelle LLPs to be transgenerationally inherited. Next, I will perturb oocyte health to investigate how maternally damaged LLPs contributes to offspring viability. Finally, I will identify additional long-lived proteins that are derived from maternal organelles using a biorthogonal amino acid labeling approach and compare their fates in the progeny germline with well characterized LLPs. The proposed experiments will highlight how maternally derived LLPs impact organelle function in the germline of ensuing progeny. In addition, these studies will shed light on how organelle continuity is maintained between generations and aim to reveal specialized quality control pathways in the germline.