Evolution of the Biophysical Properties of the Septin Cytoskeleton

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。据估计，地球上真菌种类的数量从150万到500多万不等，据认为，可能有超过90%的真菌尚未被识别。迄今为止，鉴定出的真菌中相对较小的比例与海洋环境有关。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非凡的能力来应对无数的压力，包括紫外线照射，有限的营养和高盐度，这些都是海洋的特征。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应对环境压力。对生长、分裂和应激反应的基本理解是理解海洋真菌如何对海洋功能做出贡献的一个缺失环节。这项工作将包括对本科生和研究生研究人员的培训，以及一些社区外展工作。在整个生物圈中，细胞功能与细胞形态发生密切相关。这在真菌中尤其明显，球形、卵形和菌丝状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一公里的菌丝，一个被称为septin的保守细胞骨架蛋白家族对于创造这种形态多样性是不可或缺的。尽管它们无处不在，但septin聚合物的基本生物物理性质和调控才刚刚开始被理解。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的形态和功能将在高度多样的真菌系统中进行分析，这些真菌系统被称为“黑色酵母”，是从海洋中分离出来的。真菌在这一组被认为是其中最耐受性的真核生物。通过对这些不同黑酵母菌种中septin蛋白序列变异、生物物理学和细胞生物学的比较分析，将揭示septin细胞骨架的可塑性如何支持细胞形状、功能和耐受性的多样性。本研究将从三个维度来分析这一问题：1。聚合物性质：septin丝的生物物理性质如何控制高阶结构？2. 动力学：如何使用septin动力学来雕刻组件并启用应力响应？3. 形态发生：不同的septin组合如何促进不同的细胞形态。这些问题将通过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。这项研究计划的组成部分是对本科生和研究生科学家的培训，以及一些社区外展活动。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.