High resolution approaches to defining organelle heterogeneity in Trypanosoma brucei
定义布氏锥虫细胞器异质性的高分辨率方法
基本信息
- 批准号:10511134
- 负责人:
- 金额:$ 18.42万
- 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:2022-06-10 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AffectBiochemicalBiochemical PathwayBiogenesisBiologyBiosensorCellsCellular biologyDataDetectionDiseaseDyesEnzymesEukaryotaEukaryotic CellEventExhibitsFlow CytometryFluorescenceFluorescence-Activated Cell SortingFractionationFutureGlycosomeHeterogeneityHomeostasisImaging TechniquesImmunoelectron MicroscopyIndividualKnowledgeMetabolicMetabolic PathwayMetabolismMethodsMicroscopyMicrosomesMolecularNatureOrganellesOrganismParasitesPathway interactionsPatternPersonsPharmaceutical PreparationsPlayPopulationProcessProteinsPublishingResolutionRoleScientistSorting - Cell MovementTechniquesTimeTrainingTrypanosoma brucei bruceiWorkbasedrug developmentexperimental studyfluorescence imaginginsightlight scatteringnovelperoxisomepreventreceptorresponsetool
项目摘要
ABSTRACT
Glycosomes are specialized peroxisomes of kinetoplastids that harbor multiple biochemical pathways.
Highlighting the importance of these organelles, disruption of glycosome integrity is lethal. Despite their essential
nature, our understanding of the processes involved in maintaining glycosome homeostasis is limited. For
example, we do not know the extent to which different metabolic pathways are localized together within a single
glycosome or are instead separated into distinct glycosome populations. Additionally, we do not know how these
organelles are formed. In large part, this gap in knowledge is due to a lack of experimental tools available for
studying organelle biology. Glycosomes are heterogeneous and we hypothesize that this heterogeneity reflects
both functional specialization (the localization of metabolic enzymes to different glycosome populations) and
vesicular intermediates formed during glycosome biogenesis. Biochemical fractionations and widefield
fluorescence imaging show that metabolic enzymes and proteins involved in glycosome/peroxisome biogenesis
called peroxins (Pexs) exhibit distinct localization patterns. These studies suggest that glycosomes differ in their
functional capabilities as well as their maturation status. However, the limitations of these approaches prevent
us from assigning a protein to a specific glycosome. In Aim 1, we will use superresolution imaging techniques to
quantitate the extent to which the glycosome proteins that exhibit distinct localization patterns localize to different
glycosomes. Subcellular organelles from Trypanosoma brucei are difficult to resolve biochemically and
significant cross-contamination occurs with current approaches. In Aim 2, we will develop methods to use
fluorescence activated organelle sorting (FAOS), a novel and powerful method, to purify and characterize
subcellular organelles including glycosomes. This work will dramatically advance our understanding of parasite
cell biology in several ways. It will enable the efficient, rapid isolation of organelles of higher purity than current
approaches, the separation of organelles based on their internal composition, and analysis of single organelles,
which will be useful in future studies of glycosome heterogeneity. The methods defined herein can be used to
purify organelles from other eukaryotic cells and can be expanded to include functional dyes or fluorescent
biosensors to follow metabolic function. The definitive finding that glycosomes are functionally specialized will
provide insight into metabolism and establish a foothold into defining the targeting sequences and organelle
receptors involved in establishing and maintaining this compartmentalization. The demonstration that glycosome
heterogeneity represents intermediates in the biogenesis pathway would lay the groundwork for resolving
different glycosome biogenesis pathways and the role they play in parasite biology. This work will forward our
understanding of glycosome biology as well as develop experimental approaches that can be applied to
organelle studies in other eukaryotes.
摘要
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 }}
MEREDITH T MORRIS其他文献
MEREDITH T MORRIS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('MEREDITH T MORRIS', 18)}}的其他基金
High resolution approaches to defining organelle heterogeneity in Trypanosoma brucei
定义布氏锥虫细胞器异质性的高分辨率方法
- 批准号:
10642881 - 财政年份:2022
- 资助金额:
$ 18.42万 - 项目类别:
The Cell Biology of Eukaryotic Pathogens Symposium
真核病原体细胞生物学研讨会
- 批准号:
9261153 - 财政年份:2016
- 资助金额:
$ 18.42万 - 项目类别:
相似海外基金
CAREER: Biochemical and Structural Mechanisms Controlling tRNA-Modifying Metalloenzymes
职业:控制 tRNA 修饰金属酶的生化和结构机制
- 批准号:
2339759 - 财政年份:2024
- 资助金额:
$ 18.42万 - 项目类别:
Continuing Grant
Systematic manipulation of tau protein aggregation: bridging biochemical and pathological properties
tau 蛋白聚集的系统操作:桥接生化和病理特性
- 批准号:
479334 - 财政年份:2023
- 资助金额:
$ 18.42万 - 项目类别:
Operating Grants
Diurnal environmental adaptation via circadian transcriptional control based on a biochemical oscillator
基于生化振荡器的昼夜节律转录控制的昼夜环境适应
- 批准号:
23H02481 - 财政年份:2023
- 资助金额:
$ 18.42万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Leveraging releasable aryl diazonium ions to probe biochemical systems
利用可释放的芳基重氮离子探测生化系统
- 批准号:
2320160 - 财政年份:2023
- 资助金额:
$ 18.42万 - 项目类别:
Standard Grant
Biochemical Mechanisms for Sustained Humoral Immunity
持续体液免疫的生化机制
- 批准号:
10637251 - 财政年份:2023
- 资助金额:
$ 18.42万 - 项目类别:
Structural and biochemical investigations into the mechanism and evolution of soluble guanylate cyclase regulation
可溶性鸟苷酸环化酶调节机制和进化的结构和生化研究
- 批准号:
10604822 - 财政年份:2023
- 资助金额:
$ 18.42万 - 项目类别:
Enhanced Biochemical Monitoring for Aortic Aneurysm Disease
加强主动脉瘤疾病的生化监测
- 批准号:
10716621 - 财政年份:2023
- 资助金额:
$ 18.42万 - 项目类别:
Converting cytoskeletal forces into biochemical signals
将细胞骨架力转化为生化信号
- 批准号:
10655891 - 财政年份:2023
- 资助金额:
$ 18.42万 - 项目类别:
Chemical strategies to investigate biochemical crosstalk in human chromatin
研究人类染色质生化串扰的化学策略
- 批准号:
10621634 - 财政年份:2023
- 资助金额:
$ 18.42万 - 项目类别:
EAGER: Elastic Electronics for Sensing Gut Luminal and Serosal Biochemical Release
EAGER:用于感测肠腔和浆膜生化释放的弹性电子器件
- 批准号:
2334134 - 财政年份:2023
- 资助金额:
$ 18.42万 - 项目类别:
Standard Grant














{{item.name}}会员




