SGER: The Role of Lipid Bodies in Peroxisomal Biogenesis

过氧化物酶体存在于几乎所有的真核细胞中。 它们是植物、真菌和动物中许多代谢途径所必需的细胞器。 过氧化物酶体的起源几十年来一直备受争议。 现在很清楚，过氧化物酶体可以通过裂变从预先存在的过氧化物酶体形成。 然而，有足够的证据证明过氧化物酶体组装的从头途径。 内质网（ER）已被牵连在这一途径，但其确切的作用尚未确定。 也有报告称脂质体（由ER形成）和过氧化物酶体之间存在密切联系，尽管这些观察结果的意义尚不清楚。 这个项目将测试的假设，脂质体是必不可少的过氧化物酶体在酵母从头组装。 作为第一步，将确定过氧化物酶体蛋白驻留在脂质体相关结构中的程度。 通过寻找这些结构与成熟过氧化物酶体之间的亲核-产物关系，将完成对该假设的直接检验。 进一步的确认将通过检查不能产生脂质体也不能经历预先存在的细胞器分裂的突变体中过氧化物酶体生物发生的程度来完成。 因此，该项目测试了过氧化物酶体起源的全新模型。 迄今为止，过氧化物酶体的从头起源一直是一个模糊和有争议的主题，我们的假设与文献中的几个观察结果一致，可以解决这一争议。 如果这一假设是正确的，它将推翻目前对细胞器生物发生的看法，表明脂质体能够进行这种活动。 该项目还将为高中（贫困），本科生和研究生提供实践研究经验。 研究结果将通过在国家会议上的演讲和提交给一流科学期刊来广泛传播。

Peroxisomes are found in virtually all eukaryotic cells. They are essential organelles for many metabolic pathways in plants, fungi, and animals. The origin of peroxisomes has been hotly debated for decades. It is clear now that peroxisomes can form by fission from pre-existing peroxisomes. However, there is ample evidence for a de novo pathway of peroxisomal assembly. The endoplasmic reticulum (ER) has been implicated in this pathway, although its precise role has not been established. There have also been reports of close associations between lipid bodies (which form from the ER) and peroxisomes, although the significance of these observations is not known. This project will test the hypothesis that lipid bodies are essential for the de novo assembly of peroxisomes in yeast. As a first step, the extent to which peroxisomal proteins reside in the lipid body-associated structures will be determined. The direct test for the hypothesis will be accomplished by looking for a precursor-product relationship between these structures and mature peroxisomes. Further confirmation will be accomplished by examining the extent of peroxisomal biogenesis in a mutant that cannot generate lipid bodies nor undergo fission of preexisting organelles. This project thus tests a completely new model for the origin of peroxisomes. The de novo origin of peroxisomes has been a murky and controversial subject to date, and our hypothesis is consistent with several observations in the literature and could solve this controversy. If the hypothesis is correct, it would overturn current thinking of organelle biogenesis, indicating that the lipid body is capable of this activity. The project will also provide hands-on research experience for high school (underprivileged), undergraduate, and graduate students. Results will be widely disseminated through talks at national meetings and submission to first-tier science journals.