Regulation of Mitochondrial Functions by Iron and Ceramides in C. elegans
线虫中铁和神经酰胺对线粒体功能的调节
基本信息
- 批准号:1557787
- 负责人:
- 金额:$ 99.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-07-01 至 2022-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Biological processes such as responses to stress, cell death and lifespan depend on maintaining a balance among levels of various compounds such as fats (lipids), iron and sugars. Although substantial research efforts have revealed how the levels of fats and sugars are controlled by different hormones, such as insulin, the connection of these processes to processes that regulate iron levels is poorly understood. Recently, the investigators identified cellular processes that potentially integrate the ways that iron and lipid levels are maintained. The investigators will determine the dynamics and interaction between iron homeostasis and synthesis of specific lipids (ceramides), and how these interactions impact organismal functions such as metabolism, cell death and responses to stress. A genetic model system will be used to identify novel genes involved with cellular iron and lipid homeostasis. Additionally, the investigators will incorporate their research with education by providing research opportunities and mentoring to graduate and undergraduate students. Furthermore, an outreach-based learning module will be incorporated into the existing and successful UNT Elm Fork Education Center. This science education center reaches over 20,000 visitors per year (majority are K-8th graders). By collaborating with the Elm Fork Education Center students will be exposed to the field of genetic modeling and the cellular responses to environmental stress in animals. Completion of this project will elucidate novel mechanisms regulating mitochondrial function relative to whole animal biology. The goals of this project are to dissect the pathways controlling sphingolipid/ceramide metabolism and iron regulation and to determine if sphingolipid/ceramide metabolism and iron regulation are mechanistically linked. The approach is to use the genetic model system Caenorhabditis elegans to conduct cellular, molecular and genetic analysis on mutants with altered sphingolipid/ceramide metabolism and iron regulation. The investigators will test the hypothesis that 1) central features of mitochondrial function and the response to oxygen deprivation in an intact whole organism are sphingolipid/ceramide metabolism and iron regulation; and 2) sphingolipid/ceramide metabolism and iron regulation are mechanistically linked in mitochondrial functions. To test these hypothesis the following Specific Aims will be conducted: Aim 1: Determine how ceramide biosynthesis and iron regulation impact mitochondria functions and whole organism stress responses; Aim 2: Conduct genetic suppression analyses to identify signaling pathways that interact with ceramide biosynthesis and iron regulation; Aim 3. Utilize genetic analysis to determine if neet-1 and ceramide biosynthesis mechanistically interact to regulate mitochondrial functions. The proposed research could have a transformative impact on the way sphingolipid/ceramide metabolism and iron regulation is viewed in the context of mitochondrial homeostasis. The project provides research training for graduate and undergraduate students. Furthermore, an outreach-based learning module that focuses on the genetic model system C. elegans will be offered through a program at the UNT Elm Fork Education center. This outreach program will have a broad impact since it reaches over 20,000 visitors per year.
生物过程,如对压力的反应,细胞死亡和寿命取决于保持各种化合物,如脂肪(脂质),铁和糖之间的平衡。虽然大量的研究工作已经揭示了脂肪和糖的水平是如何由不同的激素控制的,如胰岛素,但这些过程与调节铁水平的过程之间的联系却知之甚少。最近,研究人员确定了可能整合铁和脂质水平维持方式的细胞过程。研究人员将确定铁稳态和特定脂质(神经酰胺)合成之间的动态和相互作用,以及这些相互作用如何影响生物体功能,如代谢,细胞死亡和对压力的反应。一个遗传模型系统将被用来确定新的基因参与细胞铁和脂质稳态。此外,研究人员将通过为研究生和本科生提供研究机会和指导,将他们的研究与教育结合起来。此外,一个基于外展的学习模块将被纳入现有的和成功的UNT榆树叉教育中心。这个科学教育中心每年接待超过20,000名游客(大多数是K-8年级学生)。通过与榆树叉教育中心合作,学生将接触到遗传建模和动物对环境压力的细胞反应领域。该项目的完成将阐明相对于整个动物生物学调节线粒体功能的新机制。该项目的目标是剖析控制鞘脂/神经酰胺代谢和铁调节的途径,并确定鞘脂/神经酰胺代谢和铁调节是否存在机械联系。该方法是使用遗传模型系统秀丽隐杆线虫进行细胞,分子和遗传分析的突变体与改变鞘脂/神经酰胺代谢和铁调节。研究人员将检验以下假设:1)完整生物体中线粒体功能和缺氧反应的中心特征是鞘脂/神经酰胺代谢和铁调节; 2)鞘脂/神经酰胺代谢和铁调节在线粒体功能中存在机械联系。为了检验这些假设,将进行以下特定目的:目的1:确定神经酰胺生物合成和铁调节如何影响线粒体功能和整个生物体应激反应;目的2:进行遗传抑制分析,以鉴定与神经酰胺生物合成和铁调节相互作用的信号传导途径;目的3。利用遗传分析来确定neet-1和神经酰胺生物合成机制是否相互作用来调节线粒体功能。拟议的研究可能会对鞘脂/神经酰胺代谢和铁调节的方式产生变革性影响,这些影响是在线粒体稳态的背景下进行的。该项目为研究生和本科生提供研究培训。此外,基于外展的学习模块,集中在遗传模型系统C。elegans将通过UNT Elm Fork教育中心的一个项目提供。该外展计划将产生广泛的影响,因为每年有超过20,000名访客。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Pamela Padilla其他文献
A comprehensive guide to the surgical management of nonmelanoma skin cancer.
非黑色素瘤皮肤癌手术治疗的综合指南。
- DOI:
- 发表时间:
2015 - 期刊:
- 影响因子:2.6
- 作者:
J. Divine;Lilia Stefaniwksy;R. Reddy;Pamela Padilla;Thomas J. Hagele;N. Patel;B. Cherpelis - 通讯作者:
B. Cherpelis
Pamela Padilla的其他文献
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{{ truncateString('Pamela Padilla', 18)}}的其他基金
NSF-BSF: Mechanism of Cuticle Remodeling by Hypoxia
NSF-BSF:缺氧角质层重塑机制
- 批准号:
2308879 - 财政年份:2023
- 资助金额:
$ 99.27万 - 项目类别:
Continuing Grant
CAREER: Use of C. Elegans to Identify Alleles and Genotypes that Modulate Severe Anoxia Survival
职业生涯:利用线虫来识别调节严重缺氧生存的等位基因和基因型
- 批准号:
0747391 - 财政年份:2008
- 资助金额:
$ 99.27万 - 项目类别:
Standard Grant
Genetic and Cellular Analysis of C. elegans Exposed to Anoxia
缺氧环境下线虫的遗传和细胞分析
- 批准号:
0344144 - 财政年份:2004
- 资助金额:
$ 99.27万 - 项目类别:
Standard Grant
Research Starter Grant: Analysis of ODS-1 in C. elegans Exposed to Anoxia
研究启动资助:分析暴露于缺氧的线虫中的 ODS-1
- 批准号:
0307491 - 财政年份:2003
- 资助金额:
$ 99.27万 - 项目类别:
Standard Grant
NSF Minority Postdoctoral Research Fellowship for FY-1999
1999 财年 NSF 少数族裔博士后研究奖学金
- 批准号:
9973557 - 财政年份:1999
- 资助金额:
$ 99.27万 - 项目类别:
Fellowship Award
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