POST-TRANSCRIPTIONAL REGULATION OF CELL FATE IN EARLY MAMMALIAN DEVELOPMENT
早期哺乳动物发育中细胞命运的转录后调控
基本信息
- 批准号:10191941
- 负责人:
- 金额:$ 14.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-01 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:3&apos Untranslated RegionsAddressAnatomyBinding ProteinsBiosensorCell Differentiation processCell Fate ControlCell modelCellsClustered Regularly Interspaced Short Palindromic RepeatsCritical PathwaysDataDevelopmentDevelopment PlansDevelopmental BiologyEmbryoEmbryonic DevelopmentEndocytosisEnsureEnvironmentErythropoiesisFamilyFibroblast Growth FactorFive-Year PlansFutureGoalsGrantHepatobiliaryHigh-Throughput Nucleotide SequencingHuman DevelopmentImmunoprecipitationIn VitroIronIron Regulatory Protein 1Iron-Regulatory ProteinsKnowledgeLaboratoriesLeadershipLearningMapsMediatingMentored Clinical Scientist Development Award (K08)MentorsMessenger RNAMethodsMicroRNAsModelingMolecularNucleotidesOperative Surgical ProceduresOrganogenesisPathologistPathologyPathway interactionsPatternPhysiciansPlayPost-Transcriptional RegulationProcessRNA-Binding ProteinsRegulationReporterResearchResolutionRoleScientistSignal TransductionSiteStatistical MethodsStem cell pluripotencyTechnical ExpertiseTestingTrainingTranscriptbasecareer developmentcrosslinkembryonic stem cellfunctional genomicsgastrointestinalgastrulationin vivomouse modelmultidisciplinarymutantneurogenesispluripotencyprofilinregenerative therapysingle-cell RNA sequencingskillsstemstem cell biologystem cell differentiationstem cell fatestem cell self renewalstem cellstooltranscriptome
项目摘要
Post-transcriptional regulation by RNA-binding proteins (RBPs) and microRNAs (miRNAs) orchestrate diverse
molecular and cellular mechanisms that pattern early mammalian development from embryonic stem cells
(ESCs) through gastrulation and lineage commitment. The RBPs Ago2 (Argonaute-2) and IRP (iron regulatory
proteins) respectively coordinate miRNA-mediated regulation and cellular iron regulation, mechanisms essential
for the proper execution of early embryonic development. In human development, cellular iron regulation is
important for non-hematopoietic tissue development, including neurogenesis and gut development, in addition
to erythropoiesis. However, the identities and functional roles of miRNA- and IRP-bound targets in cell fate
decisions during early embryonic development are largely unknown. A comprehensive understanding of the
dynamic relationships of IRPs, miRNAs, and their functional targets during this critical developmental window is
needed and can provide a roadmap for functional rewiring in stem/progenitor cell-based regenerative therapies.
The central hypothesis of this proposal is that IRP and miRNAs function cooperatively and dynamically on targets
that are important regulators of cell fate transitions during mammalian development. As a molecular biologist
and pathologist, my long-term goal is to understand and use these integrated pathways of post-transcriptional
control to devise new tools and approaches for functional rewiring in stem/progenitor cell-based regenerative
therapies. The objective of this project is to dissect the specific roles of post-transcriptional regulation by miRNAs
and IRPs on cell fate decisions in early mammalian development and to build platforms to model cellular iron
throughout early mammalian development. This project objective will be achieved by 1) determining the impact
of IRP and miR-290-mediated regulation on Profilin-2, a known regulator of ESC differentiation, 2) identifying
and functionally dissecting the global network of bound IRP and miRNA targets, and 3) developing biosensor
platforms that model cellular iron utilization in vitro and in vivo during early embryonic development. The
proposed studies are the core components of the Mentored Clinical Scientist Development Award (K08) for Dr.
Carolyn Sangokoya. Dr. Sangokoya is a board-certified Anatomic Pathologist with subspeciality expertise in
surgical and gastrointestinal/hepatobiliary pathology. This proposal encompasses a five-year plan to address
gaps in specific research and professional skills as she transitions to independence as a physician-scientist. This
grant is a training vehicle for Dr. Sangokoya to 1) build knowledge in statistical methods for functional genomics,
2) learn and expand technical skills in generating mouse models, 3) perform single-cell RNA-sequencing studies,
and 4) develop professional scientific leadership and lab management skills in transition to leading a successful
laboratory. To achieve these goals, Dr. Sangokoya and her multidisciplinary scientific advisory and mentoring
team have devised a 5-year career development plan. The proposed training, didactics, and research in the rich
research environment at UCSF will ensure a successful and productive transition to independence.
转录后调控由rna结合蛋白(rbp)和microrna (mirna)协调
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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CAROLYN O SANGOKOYA其他文献
CAROLYN O SANGOKOYA的其他文献
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{{ truncateString('CAROLYN O SANGOKOYA', 18)}}的其他基金
POST-TRANSCRIPTIONAL REGULATION OF CELL FATE IN EARLY MAMMALIAN DEVELOPMENT
早期哺乳动物发育中细胞命运的转录后调控
- 批准号:
10366001 - 财政年份:2021
- 资助金额:
$ 14.24万 - 项目类别:
POST-TRANSCRIPTIONAL REGULATION OF CELL FATE IN EARLY MAMMALIAN DEVELOPMENT
早期哺乳动物发育中细胞命运的转录后调控
- 批准号:
10611405 - 财政年份:2021
- 资助金额:
$ 14.24万 - 项目类别:
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