Gene Expression Variability and Nuclear Territory Autonomy in Syncytia
合胞体的基因表达变异性和核域自主性
基本信息
- 批准号:10537843
- 负责人:
- 金额:$ 3.82万
- 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 2023-04-14
- 项目状态:已结题
- 来源:
- 关键词:AlgaeBehaviorBiochemicalBiochemical ProcessBiological ProcessBiologyBloodCell CycleCell NucleusCell PolarityCell physiologyCellsCellular biologyConceptionsCuesCytoplasmCytosolDiffusionDiseaseGene ExpressionGene Expression ProfileGenesGenetic TranscriptionGiant CellsGlobal ChangeGrowthHeterogeneityHumanImageLearningLifeMalignant NeoplasmsMeasuresMediatingMembraneMissionModelingMorphologyMuscleMuscle CellsNuclearPatternPhysical condensationPhysiologyPlacentaPopulationPrevalenceProcessProteinsPublic HealthRNARegulationResearchRibosomesRoleShapesSignal TransductionSourceTestingTranscriptTranscription ProcessTranscriptional RegulationTranslatingTranslationsTreesUnited States National Institutes of HealthVariantWorkcell typeembryo tissuefungushuman tissueinsightnuclear divisionoptogeneticsresponsestatisticstranscriptome sequencing
项目摘要
Title Gene expression variability and nuclear territory autonomy in syncytia
Project Summary
Syncytia are large, multinucleate cells that are found widely across biology. Algae, fungi, protists, and human
tissues like muscle and placenta are all composed of syncytia. Such organization has even been proposed to
be the ancestral eukaryotic state. Despite its prevalence across kingdoms of life, the organization and regulation
of syncytial cells remain understudied. How do multiple nuclei shape the composition and function in syncytia?
Syncytial algal and mammalian muscle cells show distinct gradients of local composition. Nuclei sharing the
same cytoplasm in these cells show distinct transcriptional profiles. Work in the Gladfelter lab showed that in the
syncytial fungus Ashbya gossypii, nuclei show asynchronous nuclear division, suggesting that cell-cycle signals
are not shared in neighboring nuclei in these cells. Overall, these pieces of evidence suggest that the cytosolic
composition in syncytial cells is highly heterogeneous despite lacking physical barriers to diffusion across the
cell, and that syncytial nuclei can show autonomy in gene expression. It is unknown how the composition of
nuclear-proximal cytosolic territories is regulated in syncytia, and how this impacts nuclear territory function.
Extensive work in the Gladfelter lab has revealed that spatial clustering and non-random localization of
transcripts underlies nuclear-autonomous division in Ashbya. Such non-random localization is mediated by the
formation of RNA-protein condensates consisting of Whi3 protein. Whi3 condensates also modulate proper
branching morphology in Ashbya by clustering transcripts involved in polar growth at hyphal tips. How Whi3
localization modulates translation from these transcripts in unknown. In general, it is unknown how nuclear
territory composition and function are regulated by local variation in transcription and translation.
In this proposal I will examine how local composition is influenced by spatial variability in transcription and
translation in the genetically tractable model syncytial fungus Ashbya. In Aim 1 I will investigate sources of
transcription variation between nuclei and the consequences of such variation on local territory function. By
modulating transcription locally, I expect to establish the role of nuclear autonomous transcription in controlling
variation in local biochemical function. In Aim 2 I will investigate the role of Whi3 condensation on spatial biases
in translation. I will use manipulate Whi3 condensation locally to study the impact of condensates on local
translation. In Aim 3 I will investigate which biochemical processes are globally coordinated versus those that
are locally responsive across syncytial nuclei. This will reveal nuclear populations that show active or repressed
transcription, and biochemical processes that are locally regulated. Upon the completion of this work, I expect to
dissect the contribution of variation in transcription and regulated local translation in shaping the functionality of
nucleus-associated cytosolic territories in Ashbya. The rationale for the proposed work is that it will provide
insight into how local autonomy of nuclear territories can shape the biology of large multinucleate cells. Overall,
this work will provide insights into organization and regulation of a widespread yet poorly understood cell-type.
合胞体中基因表达变异与核领域自主
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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Ameya Pranav Jalihal其他文献
Ameya Pranav Jalihal的其他文献
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{{ truncateString('Ameya Pranav Jalihal', 18)}}的其他基金
Gene Expression Variability and Nuclear Territory Autonomy in Syncytia
合胞体的基因表达变异性和核域自主性
- 批准号:
10707924 - 财政年份:2022
- 资助金额:
$ 3.82万 - 项目类别:
Gene Expression Variability and Nuclear Territory Autonomy in Syncytia
合胞体的基因表达变异性和核域自主性
- 批准号:
10889832 - 财政年份:2022
- 资助金额:
$ 3.82万 - 项目类别:
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