SGER: The Role of Lipid Bodies in Peroxisomal Biogenesis

在几乎所有的真核细胞中都发现了过氧化物体。它们是植物、真菌和动物许多代谢途径所必需的细胞器。过氧酶体的起源几十年来一直是人们激烈争论的问题。现在很清楚的是，过氧酶体可以由先前存在的过氧酶体通过分裂形成。然而，有充分的证据证明了过氧化体组装的从头途径。内质网(ER)参与了这一途径，尽管其确切的作用尚未确定。也有报道称脂质小体(由内质网形成)和过氧化物体之间存在密切联系，尽管这些观察结果的意义尚不清楚。这个项目将检验这样的假设，即脂体对于酵母中过氧化物体的从头组装是必不可少的。作为第一步，将确定过氧化体蛋白在脂体相关结构中的驻留程度。对这一假说的直接检验将通过寻找这些结构和成熟的过氧化酶体之间的前体-产物关系来完成。进一步的确认将通过检查一个不能产生脂体也不能经历先前存在的细胞器的分裂的突变体的过氧体生物发生的程度来完成。因此，该项目测试了一种全新的过氧化酶体起源模型。到目前为止，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，并可能解决这一争议。如果这一假说是正确的，它将颠覆目前关于细胞器生物发生的想法，表明脂体能够进行这一活动。该项目还将为高中(贫困学生)、本科生和研究生提供实践研究经验。结果将通过在国家会议上的演讲和提交给一流的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.