Regulation of Yeast Filamentous Morphogenesis By Inositol Polyphosphates
肌醇多磷酸对酵母丝状形态发生的调节
基本信息
- 批准号:1902359
- 负责人:
- 金额:$ 44.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-01 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
This project will define critical steps in fungal growth for the development of antifungal agents, relevant to the agricultural industry and other economic sectors. Fungal cells regulate their growth in response to nutrient availability in part by controlling the abundance of molecules that can act as messengers within cells. One such class of messengers, inositol polyphosphates (InsPs), contribute to the control of cell shape and the resulting physical properties of fungal biofilm mats, resistant sheets of fungal cells that form on plastics and other solid surfaces. Little is known about the regulation of these InsP messengers or the cell components to which they attach. This research will provide missing molecular and biophysical detail regarding InsP messengers and their effect on fungal biology and growth. This level of understanding is fundamental for the development of new methods to control fungal overgrowth. From an educational perspective, undergraduate students from underrepresented backgrounds will have the opportunity to receive summer training in molecular and cellular biology for the analysis of InsPs. These students will also participate in departmental events and diversity workshops to provide them with the background and foundational resources to better succeed in graduate educational settings.Cells use metabolite levels to signal conditions of nutritional stress for the regulation of cell shape, cell cycle progression, gene expression, and polarized growth, but the molecular basis of this signaling is incompletely understood. The yeasts S. cerevisiae and C. albicans are highly informative fungal models of cell signaling. Under conditions of nutrient limitation, yeast cells form extended and connected filaments as pseudohyphae, hyphae, and biofilms, through a signaling network recently found to involve the regulatory control of an important and conserved metabolite, inositol polyphosphate (InsP). InsPs are phosphorylated variants of the six-carbon inositol ring that regulate diverse cell processes. Pathways required for yeast cell growth and filamentation are required for wild-type InsP levels under conditions of nutrient limitation, and the genes encoding InsP biosynthetic enzymes are required for wild-type filamentation. In particular, the respective levels of pyrophosphorylated InsP species with doubly phosphorylated carbon residues in the inositol ring correlates strongly with the degree of filamentation in S. cerevisiae. This research will dissect the molecular mechanisms linking the regulation of filamentation and biofilm formation with InsP signaling. The molecular function of the conserved AMPK family kinase Snf1p in modulating activity of the InsP kinases Kcs1p and Vip1p will be determined. This research identifies the role of InsPs in controlling the protein composition and structure of the plasma membrane. The effect of InsP signaling on the filamentous morphology and rheological properties of biofilms in C. albicans will be quantified. Collectively, the project investigates conserved signaling pathways regulating InsP abundance and new downstream effectors of this regulatory network. Further, the research quantifies the effects of InsP signaling on the biophysics of C. albicans biofilms, presenting an important advancement in understanding the molecular basis of this economically significant fungal multicellular structure.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.
该项目将确定真菌生长的关键步骤,以开发与农业和其他经济部门相关的抗真菌剂。真菌细胞通过控制细胞内作为信使的分子的丰度来调节其生长,以响应营养的可用性。一类这样的信使,肌醇多磷酸(InsPs),有助于控制细胞形状和真菌生物膜垫,在塑料和其他固体表面上形成的真菌细胞的抗性片的物理性质。关于这些InsP信使或它们所附着的细胞成分的调节知之甚少。这项研究将提供有关InsP信使及其对真菌生物学和生长的影响的分子和生物物理学细节。这种理解水平是控制真菌过度生长的新方法的发展的基础。从教育的角度来看,来自代表性不足背景的本科生将有机会接受分子和细胞生物学的暑期培训,以分析InsPs。这些学生还将参加部门活动和多样性研讨会,为他们提供背景和基础资源,以更好地在研究生教育环境中取得成功。细胞使用代谢物水平来信号营养应激条件,以调节细胞形状,细胞周期进程,基因表达和极化生长,但这种信号传导的分子基础尚不完全清楚。酵母S.酿酒酵母和C.白色念珠菌是细胞信号传导的高度信息化的真菌模型。 在营养限制的条件下,酵母细胞通过最近发现的信号网络形成延伸和连接的丝状体,如假菌丝、菌丝和生物膜,所述信号网络涉及重要且保守的代谢产物肌醇多磷酸(InsP)的调节控制。InsPs是调节多种细胞过程的六碳肌醇环的磷酸化变体。酵母细胞生长和表达所需的途径是营养限制条件下野生型InsP水平所需的,并且编码InsP生物合成酶的基因是野生型表达所需的。特别是,在肌醇环中具有双磷酸化碳残基的焦磷酸化InsP种类的各自水平与S中的双磷酸化程度强烈相关。啤酒。本研究将剖析InsP信号转导调控细菌表型和生物膜形成的分子机制。将确定保守的AMPK家族激酶Snf1p在调节InsP激酶Kcs1p和Vip1p活性中的分子功能。这项研究确定了InsPs在控制质膜蛋白质组成和结构中的作用。研究了InsP信号对C.将对白色念珠菌进行定量。总的来说,该项目研究了保守的信号通路调节InsP丰度和新的下游效应器的调控网络。此外,该研究量化了InsP信号对C.该奖项反映了NSF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。
项目成果
期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Filamentation Regulatory Pathways Control Adhesion-Dependent Surface Responses in Yeast
- DOI:10.1534/genetics.119.302004
- 发表时间:2019-07-01
- 期刊:
- 影响因子:3.3
- 作者:Chow, Jacky;Starr, Izzy;Cullen, Paul J.
- 通讯作者:Cullen, Paul J.
Rheology of Candida albicans fungal biofilms
白色念珠菌真菌生物膜的流变学
- DOI:10.1122/8.0000427
- 发表时间:2022
- 期刊:
- 影响因子:3.3
- 作者:Beckwith, Joanne K.;Ganesan, Mahesh;VanEpps, J. Scott;Kumar, Anuj;Solomon, Michael J.
- 通讯作者:Solomon, Michael J.
A Stress-Responsive Signaling Network Regulating Pseudohyphal Growth and Ribonucleoprotein Granule Abundance in Saccharomyces cerevisiae
调节酿酒酵母假菌丝生长和核糖核蛋白颗粒丰度的应激反应信号网络
- DOI:10.1534/genetics.119.302538
- 发表时间:2019
- 期刊:
- 影响因子:3.3
- 作者:Mutlu, Nebibe;Sheidy, Daniel T.;Hsu, Angela;Jeong, Han Seol;Wozniak, Katherine J.;Kumar, Anuj
- 通讯作者:Kumar, Anuj
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Anuj Kumar其他文献
Positional Obstructive Sleep Apnoea
位置性阻塞性睡眠呼吸暂停
- DOI:
10.5005/ijcdas-63-2-89 - 发表时间:
2022 - 期刊:
- 影响因子:0
- 作者:
Anuj Kumar;K. Garg;Fnu Deepali;Varinder Saini;Prakhar Agarwal;I. Singh - 通讯作者:
I. Singh
Polymeric drug careers through covalent attachment and encapsulation for controlled delivery purposes
通过共价连接和封装实现控制递送目的的聚合物药物事业
- DOI:
10.1007/s12588-014-9091-y - 发表时间:
2014 - 期刊:
- 影响因子:0
- 作者:
Anuj Kumar;Ujjwal Rewati Raman;U. Ojha - 通讯作者:
U. Ojha
Analytical bounds on the heat transport in internally heated convection
内部加热对流热传输的解析界限
- DOI:
10.1017/jfm.2022.170 - 发表时间:
2021 - 期刊:
- 影响因子:3.7
- 作者:
Anuj Kumar;A. Arslan;Giovanni Fantuzzi;John Craske;A. Wynn - 通讯作者:
A. Wynn
Development and Characterization of Rice Genotypes for Water Use Efficiency and Drought Resistance
- DOI:
- 发表时间:
2017 - 期刊:
- 影响因子:0
- 作者:
Anuj Kumar - 通讯作者:
Anuj Kumar
Non-equilibrium growth patterns of carbohydrate and saccharin in gel media
凝胶介质中碳水化合物和糖精的非平衡生长模式
- DOI:
- 发表时间:
1997 - 期刊:
- 影响因子:0
- 作者:
I. Das;Archana Sharma;Anuj Kumar;R. Lall - 通讯作者:
R. Lall
Anuj Kumar的其他文献
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{{ truncateString('Anuj Kumar', 18)}}的其他基金
Organelle DB / Organelle View: A Community Resource of Protein Localization and Function
细胞器数据库/细胞器视图:蛋白质定位和功能的社区资源
- 批准号:
0543017 - 财政年份:2006
- 资助金额:
$ 44.34万 - 项目类别:
Standard Grant