The Role of Lipids in Different Cell Fates

脂质在不同细胞命运中的作用

基本信息

  • 批准号:
    1817468
  • 负责人:
  • 金额:
    $ 73.07万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-07-01 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

This project will shed new light on the role of lipids in cell biology. Lipids form barriers that define cells and their internal compartments. They are also recently recognized for their critical roles as signaling molecules, regulating cellular processes. It is now clear that cells produce thousands of unique lipid species with diverse functions. However, the individual functions of these lipid species remain unclear. Within this context, this project applies state-of-the-art chemical biology and analytical approaches to investigate the role of specific lipids in different cell fates. By doing so, this study will reveal novel mechanisms underlying fundamental cellular processes. The comprehensive methodological tools employed in this project allows training a globally competitive workforce across the educational spectrum involving participation of underrepresented student groups and teachers in research and scientific inquiry.This project will elucidate the function of lipids during cell death, providing a better fundamental understanding of different types of programmed cell death, which are physiologically critical processes that are involved in maintaining cellular homeostasis. These goals will be achieved using an integrative set of approaches that merges lipidomics, transcriptomics, and proteomics with structure-specific bioorthogonal lipids probes. This research program will focus on i) the function of distinct ceramides based on their structure during apoptosis and ii) the role of very long chain fatty acids in permeabilization of the membranes during necroptosis. A two component integration will be used for these studies: i) Determine substrate specificity of different ceramide synthases and investigate the function of specific ceramides using structure-specific probes and genetic perturbations, ii) determine the localization and interaction partners of very long chain fatty acids during necroptosis. The objectives will elucidate the function of lipids during cell death, providing a better fundamental understanding of these physiologically critical processes. The results from this work will shed light on the functional roles of specific lipids based on their precise chemical structure. They will specifically elucidate the role of individual ceramides and fatty acids on membrane permeabilization and their interaction with other biomolecules during apoptosis and necroptosis. This knowledge will open the door to novel studies investigating the impact of structural specificity on lipid function in cells.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.
该项目将揭示脂质在细胞生物学中的作用。脂质形成限定细胞及其内部隔室的屏障。它们最近也被认为是信号分子,调节细胞过程的关键作用。现在很清楚,细胞产生数千种具有不同功能的独特脂质种类。然而,这些脂质种类的个体功能仍不清楚。在此背景下,该项目应用最先进的化学生物学和分析方法来研究特定脂质在不同细胞命运中的作用。通过这样做,这项研究将揭示基本细胞过程的新机制。该项目采用的综合方法工具可以在教育领域培养具有全球竞争力的劳动力,包括参与研究和科学探究的代表性不足的学生团体和教师。该项目将阐明脂质在细胞死亡过程中的功能,提供对不同类型的程序性细胞死亡的更好的基本理解,其是参与维持细胞内稳态的生理学关键过程。这些目标将使用一套整合的方法来实现,该方法将脂质组学,转录组学和蛋白质组学与结构特异性生物正交脂质探针相结合。该研究计划将侧重于i)基于其结构的不同神经酰胺在细胞凋亡过程中的功能,以及ii)极长链脂肪酸在坏死性凋亡过程中膜透化中的作用。这些研究将使用双组分整合:i)确定不同神经酰胺脱氢酶的底物特异性,并使用结构特异性探针和遗传扰动研究特定神经酰胺的功能,ii)确定坏死性凋亡期间极长链脂肪酸的定位和相互作用伴侣。这些目标将阐明脂质在细胞死亡过程中的功能,为这些生理关键过程提供更好的基本理解。这项工作的结果将揭示基于其精确化学结构的特定脂质的功能作用。他们将具体阐明个别神经酰胺和脂肪酸对膜透化的作用,以及它们在细胞凋亡和坏死性凋亡过程中与其他生物分子的相互作用。这一知识将为研究结构特异性对细胞脂质功能的影响的新研究打开大门。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(13)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Protein acylation by saturated very long chain fatty acids and endocytosis are involved in necroptosis.
  • DOI:
    10.1016/j.chembiol.2021.03.012
  • 发表时间:
    2021-09-16
  • 期刊:
  • 影响因子:
    8.6
  • 作者:
    Pradhan AJ;Lu D;Parisi LR;Shen S;Berhane IA;Galster SL;Bynum K;Monje-Galvan V;Gokcumen O;Chemler SR;Qu J;Kay JG;Atilla-Gokcumen GE
  • 通讯作者:
    Atilla-Gokcumen GE
Solving the enigma: Mass spectrometry and small molecule probes to study sphingolipid function
解开谜团:质谱法和小分子探针研究鞘脂功能
  • DOI:
    10.1016/j.cbpa.2021.05.001
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    7.8
  • 作者:
    Millner, Alec;Atilla-Gokcumen, G. Ekin
  • 通讯作者:
    Atilla-Gokcumen, G. Ekin
Promotion of plasmalogen biosynthesis reverse lipid changes in a Barth Syndrome cell model
Untargeted Lipidomics Highlight the Depletion of Deoxyceramides during Therapy‐Induced Senescence
非靶向脂质组学强调治疗过程中脱氧神经酰胺的消耗——诱导衰老
  • DOI:
    10.1002/pmic.202000013
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Millner, Alec;Lizardo, Darleny Y.;Atilla‐Gokcumen, Gunes Ekin
  • 通讯作者:
    Atilla‐Gokcumen, Gunes Ekin
Omics approaches to better understand the molecular mechanism of necroptosis and their translational implications
组学方法可以更好地理解坏死性凋亡的分子机制及其转化意义
  • DOI:
    10.1039/d2mo00318j
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Pradhan, Apoorva J.;Atilla-Gokcumen, G. Ekin
  • 通讯作者:
    Atilla-Gokcumen, G. Ekin
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Gunes Atilla-Gokcumen其他文献

Gunes Atilla-Gokcumen的其他文献

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{{ truncateString('Gunes Atilla-Gokcumen', 18)}}的其他基金

Fundamental Studies on the Regulation and Interaction of Ceramides in Cellular Senescence and Cell Death
神经酰胺在细胞衰老和细胞死亡中的调控和相互作用的基础研究
  • 批准号:
    2314338
  • 财政年份:
    2023
  • 资助金额:
    $ 73.07万
  • 项目类别:
    Standard Grant
SusChEM: Time-series Characterization and Modeling of Non-model Microalgae at the Systems-level for Sustainable Chemical Production
SusChEM:可持续化学生产系统级非模型微藻的时间序列表征和建模
  • 批准号:
    1438172
  • 财政年份:
    2014
  • 资助金额:
    $ 73.07万
  • 项目类别:
    Standard Grant

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TTYH1 在神经胶质细胞动员脂质和 ApoE 中的作用:对大脑衰老和神经退行性变的影响
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