Investigating the mechanisms of peroxisome homeostasis
研究过氧化物酶体稳态机制
基本信息
- 批准号:10680467
- 负责人:
- 金额:$ 37.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:ATP phosphohydrolaseAgingAllelesAutophagocytosisBindingBiogenesisBlindnessBone DiseasesCellsCellular biologyDiseaseEnvironmentEnzymesGeneticGoalsHealthHomeostasisHumanKidney DiseasesKnowledgeLiver diseasesMaintenanceMembraneMetabolicMolecularMorphologyMutationNerve DegenerationOrganellesPHEX proteinProcessProtein BiochemistryReactionResearchSignal PathwayStressTechniquesYeastshearing impairmentimprovednovelperoxisome
项目摘要
Title: Investigating the mechanisms of peroxisome homeostasis
Abstract
The overarching goal of my lab is to understand how cells make and maintain peroxisomes, a
ubiquitous membrane-bound organelle that harbors specialized metabolic reactions.
Peroxisomes are both versatile and dynamic: cells use them to adapt to their environment, and
thus can rapidly remodel their peroxisomes by altering enzyme content, morphology, and
number through peroxisome-specific autophagy and de novo biogenesis. Approximately 35 Pex
proteins are known to contribute to peroxisome formation and maintenance, yet the
mechanisms by which they act are not resolved at a molecular level. Furthermore, we are likely
missing many important players, especially in human cells, and this lack of basic mechanistic
knowledge hinders our understanding of how peroxisome contribute to human health, both in
rare, genetic Peroxisome Biogenesis Disorders (PBDs), and during the aging process. Our
approach is to use techniques in protein biochemistry and yeast cell biology to dissect the
mechanism of the Pex proteins, particularly focusing on the AAA-ATPase Pex1/Pex6. We aim
to identify the full repertoire of Pex1/Pex6’s endogenous substrates and the features that are
important for substrate selection. Since mutations in Pex1/Pex6 cause the majority of PBDs, we
are further focused on using disease-causing alleles to understand Pex1/Pex6 function in the
human cells and the cellular consequences of peroxisome stress induced by these alleles.
Finally, we have identified novel regulators of peroxisome homeostasis in human cells, and are
now exploring how peroxisome function integrates with the implicated canonical signaling
pathways. We anticipate that this research will improve our understanding of how peroxisomes
contribute to human health and disease.
研究过氧化物酶体内平衡的机制
摘要
我的实验室的首要目标是了解细胞是如何制造和维持过氧化物体的
无处不在的膜结合细胞器,具有特殊的代谢反应。
过氧化物体既是多功能的,也是动态的:细胞利用它们来适应环境,并且
因此可以通过改变酶的含量、形态和结构来快速重塑它们的过氧化物体
通过过氧化物酶体特异的自噬和从头生物发生的数量。约35像素
已知蛋白质有助于过氧化酶体的形成和维持,但
它们的作用机制不是在分子水平上解决的。此外,我们很可能
缺少许多重要的角色,特别是在人类细胞中,以及这种基本机制的缺乏
知识阻碍了我们理解过氧化物酶如何有助于人类健康,无论是在
罕见的遗传性过氧化物体生物发生障碍(PBD),以及在衰老过程中。我们的
方法是使用蛋白质生物化学和酵母细胞生物学的技术来剖析
Pex蛋白的作用机制,尤其是AAA-ATPase Pex1/Pex6。我们的目标是
确定Pex1/Pex6‘S内源底物的完整谱系及其特征
对于底物的选择很重要。由于Pex1/Pex6的突变导致了大多数的多发性骨髓疾病,我们
进一步侧重于利用致病等位基因来理解Pex1/Pex6在
人类细胞和由这些等位基因引起的过氧化物体应激的细胞后果。
最后,我们已经确定了人类细胞中过氧化物酶体内平衡的新调节器,并且是
现在正在探索过氧化体功能如何与所涉及的正则信号相结合
小路。我们预计这项研究将提高我们对过氧化物酶如何
有助于人类的健康和疾病。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Brooke Meghan Gardner其他文献
Brooke Meghan Gardner的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Brooke Meghan Gardner', 18)}}的其他基金
Investigating the mechanisms of peroxisome homeostasis
研究过氧化物酶体稳态机制
- 批准号:
10808484 - 财政年份:2022
- 资助金额:
$ 37.73万 - 项目类别:
Investigating the role of AAA+-ATPases in peroxisome biology
研究 AAA -ATP 酶在过氧化物酶体生物学中的作用
- 批准号:
10245266 - 财政年份:2017
- 资助金额:
$ 37.73万 - 项目类别:
Investigating the role of AAA+-ATPases in peroxisome biology
研究 AAA -ATP 酶在过氧化物酶体生物学中的作用
- 批准号:
10001560 - 财政年份:2017
- 资助金额:
$ 37.73万 - 项目类别:
相似海外基金
Interplay between Aging and Tubulin Posttranslational Modifications
衰老与微管蛋白翻译后修饰之间的相互作用
- 批准号:
24K18114 - 财政年份:2024
- 资助金额:
$ 37.73万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
EMNANDI: Advanced Characterisation and Aging of Compostable Bioplastics for Automotive Applications
EMNANDI:汽车应用可堆肥生物塑料的高级表征和老化
- 批准号:
10089306 - 财政年份:2024
- 资助金额:
$ 37.73万 - 项目类别:
Collaborative R&D
The Canadian Brain Health and Cognitive Impairment in Aging Knowledge Mobilization Hub: Sharing Stories of Research
加拿大大脑健康和老龄化认知障碍知识动员中心:分享研究故事
- 批准号:
498288 - 财政年份:2024
- 资助金额:
$ 37.73万 - 项目类别:
Operating Grants
Baycrest Academy for Research and Education Summer Program in Aging (SPA): Strengthening research competencies, cultivating empathy, building interprofessional networks and skills, and fostering innovation among the next generation of healthcare workers t
Baycrest Academy for Research and Education Summer Program in Aging (SPA):加强研究能力,培养同理心,建立跨专业网络和技能,并促进下一代医疗保健工作者的创新
- 批准号:
498310 - 财政年份:2024
- 资助金额:
$ 37.73万 - 项目类别:
Operating Grants
関節リウマチ患者のSuccessful Agingに向けたフレイル予防対策の構築
类风湿性关节炎患者成功老龄化的衰弱预防措施的建立
- 批准号:
23K20339 - 财政年份:2024
- 资助金额:
$ 37.73万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Life course pathways in healthy aging and wellbeing
健康老龄化和福祉的生命历程路径
- 批准号:
2740736 - 财政年份:2024
- 资助金额:
$ 37.73万 - 项目类别:
Studentship
NSF PRFB FY 2023: Connecting physiological and cellular aging to individual quality in a long-lived free-living mammal.
NSF PRFB 2023 财年:将生理和细胞衰老与长寿自由生活哺乳动物的个体质量联系起来。
- 批准号:
2305890 - 财政年份:2024
- 资助金额:
$ 37.73万 - 项目类别:
Fellowship Award
I-Corps: Aging in Place with Artificial Intelligence-Powered Augmented Reality
I-Corps:利用人工智能驱动的增强现实实现原地老龄化
- 批准号:
2406592 - 财政年份:2024
- 资助金额:
$ 37.73万 - 项目类别:
Standard Grant
McGill-MOBILHUB: Mobilization Hub for Knowledge, Education, and Artificial Intelligence/Deep Learning on Brain Health and Cognitive Impairment in Aging.
McGill-MOBILHUB:脑健康和衰老认知障碍的知识、教育和人工智能/深度学习动员中心。
- 批准号:
498278 - 财政年份:2024
- 资助金额:
$ 37.73万 - 项目类别:
Operating Grants
Welfare Enhancing Fiscal and Monetary Policies for Aging Societies
促进老龄化社会福利的财政和货币政策
- 批准号:
24K04938 - 财政年份:2024
- 资助金额:
$ 37.73万 - 项目类别:
Grant-in-Aid for Scientific Research (C)