Understanding mechanisms of cellular geometry scaling

了解细胞几何缩放的机制

• 批准号: BB/T000481/1
• 负责人: Snezhana Oliferenko
• 金额: $ 52.53万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT000481%2F1
• 关键词: Understanding; mechanisms; cellular; geometry; scaling

All life on Earth is made of cells. Intricately organized assemblies of different types of cells make up complex multicellular organisms such as humans or plants. Simpler organisms including yeasts or protozoa live as single cells. Cells come in an astonishing diversity of shapes optimized for their specific function. A cell can grow to different size, depending on the amount of nutrients or other signals in the environment. If specific shape is important, how do cells make sure that it remains the same across different sizes? This is an interesting biological and engineering problem that can be solved by understanding how the intrinsic cellular polarity machinery that generates cell shape by restricting growth to certain sites on the cellular membrane, can decrease or increase the sizes of these growth zones in response to changes in cellular volume. We call this property cellular geometry scaling. It is incredibly widespread in biology but we know very little about it.We will use a simple unicellular fungal organism called Schizosaccharomyces japonicus (S. japonicus) to understand how cells scale their shape. It is a great system for addressing this problem because it grows fast, is easily amenable to genetic manipulations and, of course, exhibits very robust scaling. We previously found that a regulator of the cellular polarity machinery, a protein called Rga4, was critical for scaling. If S. japonicus does not have Rga4, it cannot scale down when nutrients become scarce and dies, demonstrating that the ability to scale is really important. Now we propose to obtain mechanistic explanation for Rga4 function in scaling. Our program will consist of two interrelated objectives. First, we will understand how cellular polarity changes during scaling and how Rga4 contributes to these changes. We will also probe the relationship between Rga4 and a protein called Tea4 that normally functions to landmark growth at specific membrane sites. In the second objective we will investigate how cells regulate Rga4 by phosphorylation to promote scaling when required. Phosphorylation is one of the most important modifications regulating protein function through changes in conformation and we will additionally look at phosphoregulation of many more cellular proteins to reveal hidden connections between different parts of cellular physiology important for scaling.It is essential to do this type of fundamental research in a simple organism because it provides important insights into molecular underpinnings of polarized growth and scaling in all eukaryotic cells, from humans to plants. The answers we get may open entirely new possibilities in dealing with devastating fungal pathogens, which rely on changing their size and shape to infect their hosts.

地球上的所有生命都是由细胞组成的。不同类型细胞的复杂组织组合构成了复杂的多细胞生物体，如人类或植物。较简单的生物体，包括酵母或原生动物，以单细胞形式生活。细胞有着惊人的多样性，形状为它们的特定功能而优化。细胞可以生长到不同的大小，这取决于环境中营养物质或其他信号的量。如果特定的形状很重要，那么细胞如何确保它在不同尺寸下保持相同？这是一个有趣的生物学和工程学问题，可以通过理解内在的细胞极性机制来解决，该机制通过将生长限制在细胞膜上的某些位点来产生细胞形状，可以响应于细胞体积的变化来减少或增加这些生长区的大小。我们称此属性为细胞几何缩放。它在生物学中非常广泛，但我们对它知之甚少。了解细胞如何缩放其形状。这是解决这个问题的一个很好的系统，因为它生长迅速，很容易进行基因操作，当然，它表现出非常强大的规模。我们以前发现，细胞极性机制的调节因子，一种名为Rga 4的蛋白质，对缩放至关重要。如果S.但它没有Rga 4，当营养物质变得稀缺和死亡时，它不能缩小规模，这表明规模化的能力非常重要。现在，我们建议获得Rga 4在标度中的作用的机制解释。我们的计划将包括两个相互关联的目标。首先，我们将了解细胞极性在缩放过程中如何变化，以及Rga 4如何促成这些变化。我们还将探索Rga 4和一种名为Tea 4的蛋白质之间的关系，该蛋白质通常在特定的膜位点上起标志性生长的作用。在第二个目标中，我们将研究细胞如何通过磷酸化调节Rga4，以在需要时促进缩放。磷酸化是通过构象变化调节蛋白质功能的最重要的修饰之一，我们还将研究更多细胞蛋白质的磷酸化调节，以揭示对缩放重要的细胞生理学不同部分之间的隐藏联系。在简单的生物体中进行这种类型的基础研究是必不可少的，因为它提供了对极化生长和缩放的分子基础的重要见解。从人类到植物的所有真核细胞。我们得到的答案可能会为应对毁灭性的真菌病原体开辟全新的可能性，这些病原体依赖于改变它们的大小和形状来感染宿主。

项目成果

Peroxisomal compartmentalization of amino acid biosynthesis reactions imposes an upper limit on compartment size.

氨基酸生物合成反应的过氧化物酶体区室化对区室大小施加了上限。

• DOI: 10.25418/crick.24125613
• 发表时间: 2023
• 作者: Gu Y

Telomere-to-telomere Schizosaccharomyces japonicus genome assembly reveals hitherto unknown genome features

• DOI: 10.1002/yea.3912
• 发表时间: 2024-03-07
• 期刊: YEAST
• 影响因子: 2.6
• 作者: Etherington，Graham J.;Wu，Pei-Shang;Nieduszynski，Conrad A.
• 通讯作者: Nieduszynski，Conrad A.

Diacylglycerol at the inner nuclear membrane fuels nuclear envelope expansion in closed mitosis

内核膜上的二酰基甘油促进闭合有丝分裂中的核膜扩张

• DOI: 10.1101/2022.06.01.494365
• 发表时间: 2022
• 作者: Foo S