Evolution of the Biophysical Properties of the Septin Cytoskeleton

Septin细胞骨架生物物理特性的演变

• 批准号: 2401042
• 负责人: Amy Gladfelter
• 金额: $ 105.24万
• 依托单位: Duke University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-10-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2401042&HistoricalAwards=false
• 关键词: Evolution; Biophysical; Properties; Septin; Cytoskeleton

Fungi are integral to the productivity of all terrestrial ecosystems as they play critical roles in nutrient cycling, soil structure and as parasites and symbionts. The estimates for the number of fungal species on the planet range from 1.5 to over 5 million and it is thought that likely over 90% of fungi remain to be identified. To date, a relatively small percentage of the identified fungi are associated with marine environments. However, fungi have been found from the surface of the ocean to depths of many kilometers in ocean sediment, and these organisms have potential key roles in carbon cycling and degradation of anthropogenic materials. Fungi that survive in the marine environment have remarkable abilities to respond to the myriad of stresses, including UV exposure, limited nutrients and high salinity that are features of the ocean. This work examines how marine fungi cope with environmental stresses by changing cell shapes and controlling how the cells divide. Fundamental understanding of growth, division and stress response is a missing link to understanding how marine fungi can contribute to the function of oceans. The work will involve the training of undergraduate and graduate student researchers along with several community outreach efforts.Cell function is intimately tied to cell morphogenesis across the biosphere. This is especially clear in fungi where combinations of spherical, ovoid and hyphal-shaped cells build diverse structures across many scales. From micrometer-sized spores, centimeter-sized mushrooms and kilometer-spanning hyphae, a conserved family of cytoskeletal proteins called septins is integral to creating this morphological diversity. Despite their ubiquity, the basic biophysical properties and regulation of septin polymers are only beginning to be understood. This project links biophysical properties of septin polymers at the nanometer scale to their function in cell morphology at the micron scale. Septin form and function will be analyzed across highly morphologically diverse fungal systems called “black yeasts” that were isolated from the ocean. Fungi in this group are considered to be amongst the most stress tolerant eukaryotes. Comparative analysis of protein sequence variation, biophysics and cell biology of septins in these diverse black yeast species will reveal how plasticity in the septin cytoskeleton supports diversity in cell shape, function and stress tolerance. The research will analyze this problem from three scales: 1. Polymer properties: How do biophysical properties of septin filaments control higher-order structures? 2. Dynamics: How are septin dynamics used to sculpt assemblies and enable stress responses? 3. Morphogenesis: How do different septin assemblies promote distinct cell morphologies. These questions will be addressed using interdisciplinary approaches including biochemical reconstitution, advanced live cell imaging, molecular genetics and quantitative modeling. Integral to this research plan is the training of undergraduate and graduate student scientists, along with several community outreach activities.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

真菌是所有陆地生态系统生产力不可或缺的组成部分，因为它们在养分循环、土壤结构以及作为寄生虫和共生体方面发挥着关键作用。 地球上真菌物种的数量估计在150万到500万之间，据认为可能有超过90%的真菌仍有待鉴定。 迄今为止，相对较小比例的已确定真菌与海洋环境有关。然而，从海洋表面到海洋沉积物中数千米深处都发现了真菌，这些生物在碳循环和人为物质降解中具有潜在的关键作用。 在海洋环境中生存的真菌具有应对各种压力的非凡能力，包括紫外线照射、有限的营养和海洋特有的高盐度。 这项工作研究了海洋真菌如何通过改变细胞形状和控制细胞分裂来科普环境压力。 对生长、分裂和应激反应的基本理解是理解海洋真菌如何促进海洋功能的一个缺失环节。 这项工作将包括对本科生和研究生研究人员的培训，沿着几项社区外展工作。 这在真菌中尤其明显，其中球形，卵形和菌丝形细胞的组合在许多尺度上构建了不同的结构。从微米大小的孢子，厘米大小的蘑菇和跨越菌丝的菌丝，一个保守的细胞骨架蛋白家族称为septins是创造这种形态多样性不可或缺的。 尽管它们普遍存在，但Septin聚合物的基本生物物理特性和调节才刚刚开始被理解。 该项目将Septin聚合物在纳米尺度上的生物物理特性与其在微米尺度上的细胞形态功能联系起来。 Septin的形式和功能将在从海洋中分离出来的被称为“黑酵母”的高度形态多样的真菌系统中进行分析。 这一组中的真菌被认为是最耐胁迫的真核生物之一。 蛋白质序列变异，生物物理学和细胞生物学的septins在这些不同的黑酵母物种的比较分析将揭示septins细胞骨架的可塑性如何支持细胞形状，功能和耐应力的多样性。本研究将从三个维度来分析这一问题：1.聚合物性质：Septin细丝的生物物理性质如何控制高阶结构？2.动力学：分隔素动力学如何用于造型组件并实现应力响应？3.形态发生：不同的隔蛋白组件如何促进不同的细胞形态。这些问题将使用跨学科的方法来解决，包括生化重建，先进的活细胞成像，分子遗传学和定量建模。 该研究计划的组成部分是本科生和研究生科学家的培训，沿着几个社区外展活动。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。