Mechanisms of developmental buffering
发育缓冲机制
基本信息
- 批准号:10556357
- 负责人:
- 金额:$ 45.61万
- 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 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:AddressAdultAffectAnimalsBreedingBuffersCellsCounselingCraniofacial AbnormalitiesDNADNA SequenceDNA Sequence AlterationDefectDentalDevelopmentDevelopmental ProcessDiseaseDisease ManagementDorsalEpigenetic ProcessEquilibriumExperimental DesignsFingersFishesFutureGene ExpressionGene Expression RegulationGene FamilyGenesGeneticGenetic DiseasesGenetic VariationGenotypeHeadHealthHeritabilityHumanHuman GeneticsHuman GenomeIndividualInheritedLabelMeasurementMeasuresMedicalMethodsMissionModelingMutationNational Institute of Dental and Craniofacial ResearchOralOrganismOrthologous GenePathway interactionsPenetrancePhenotypeReiterated GenesReportingResearchSignal TransductionSkeletonSpecific qualifier valueStatistical Data InterpretationSymptomsSystemTestingTissuesVariantWorkZebrafishcraniofacialdisease diagnosisdisease phenotypedisorder preventionepigenomeepigenomic profilingepigenomicsfallsflexibilitygene interactiongenetic manipulationgenetic predictorsgenetic variantgenome editinggenome sequencingimprovedmembermutantmyocyte-specific enhancer-binding-factor 2Cnotch proteinnovel therapeutic interventionresponsescreeningskeletaltranscription factortranscriptomic profilingzebrafish genome
项目摘要
PROJECT SUMMARY/ABSTRACT:
The long-term objective of this proposal is to understand genetic buffering, or how some individuals overcome
the effects of a harmful genetic mutation. We generated a zebrafish model of buffering in order to understand
how individuals who should have gotten sick are somehow able to live unaffected healthy lives. In our model,
we used selective breeding to generate two strains of zebrafish that develop dramatically different head
skeletons in response to the same harmful genetic mutation. In one strain, the mutation causes severe, lethal
skeletal defects. Meanwhile, the other strain is remarkably buffered against the mutation. The buffered fish
develop essentially normal head skeletons, surviving to be fertile, viable adults. We compare these strains to
understand the natural buffering mechanisms that are present in some fish, and likely in some humans too. We
hypothesize that buffering is due to factors that tune developmental processes to restore balance. For
example, in Aim1 we will determine how DNA sequences which oppose the mutant gene can be turned down.
In Aim 2 we examine how factors encoded in the DNA which perform the same function as the mutant gene
can be turned up. In Aim 3 we will determine how changes that do not necessarily involve alterations in the
DNA sequence can buffer the harmful mutation. These three specific aims test how interacting mechanisms
function together to buffer development. We designed experiments to address these aims using state of the art
methods like genome editing and sequencing, colorful cell and tissue labeling, quantitative measurements of
large numbers of fish skeletons, and rigorous statistical analyses. The mechanisms we propose to study here
are present in many developmental systems and organisms and therefore will likely be applicable in wide-
ranging settings. This study of buffering mechanisms could lead to novel therapeutic approaches, buffering
mechanisms might be manipulated in the future to manage disease symptoms. This work will also lead to a
better understanding of the factors that make predicting genetic disease from gene sequences difficult. Thus,
this line of research will potentially inform and improve medical practices, including genetic disease
management, disease diagnosis, and counseling, falling squarely within the mission of the NIDCR to improve
dental, oral and craniofacial health through research.
项目总结/摘要:
这项建议的长期目标是了解遗传缓冲,或一些人如何克服
有害基因突变的影响我们制作了一个斑马鱼的缓冲模型,
那些本该生病的人是如何不受影响地健康生活的。在我们的模型中,
我们用选择性繁殖的方法培育出了两种头部发育完全不同的斑马鱼
同样有害的基因突变。在一种菌株中,突变导致严重的,致命的
骨骼缺陷与此同时,另一种菌株对突变有明显的缓冲作用。缓冲鱼
发育出基本上正常的头部骨骼,存活下来,成为有生育能力的成年个体。我们将这些菌株与
了解存在于一些鱼类中的自然缓冲机制,也可能存在于一些人类中。我们
假设缓冲是由于调整发育过程以恢复平衡的因素。为
例如,在Aim 1中,我们将确定如何抑制突变基因的DNA序列。
在目标2中,我们研究了DNA中编码的因子如何执行与突变基因相同的功能
可以翻起来。在目标3中,我们将确定不一定涉及改变的变化如何改变。
DNA序列可以缓冲有害突变。这三个具体目标测试了相互作用的机制
共同发挥缓冲发展的作用。我们设计了实验,以解决这些目标,使用最先进的
方法如基因组编辑和测序,彩色细胞和组织标记,
大量的鱼骨架和严格的统计分析。我们在这里研究的机制
存在于许多发育系统和生物体中,因此可能适用于广泛的
测距设置。这项缓冲机制的研究可能会导致新的治疗方法,缓冲
未来可能会操纵这些机制来控制疾病症状。这项工作也将导致一个
更好地理解从基因序列预测遗传疾病的困难因素。因此,在本发明中,
这一系列研究将潜在地为包括遗传疾病在内的医疗实践提供信息和改进
管理,疾病诊断和咨询,完全属于NIDCR的使命,以改善
牙科、口腔和颅面健康。
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 }}
James Tucker Nichols其他文献
James Tucker Nichols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('James Tucker Nichols', 18)}}的其他基金
The Molecular Genetics and Cell Biology of Jaw Joint Morphogenesis
颌关节形态发生的分子遗传学和细胞生物学
- 批准号:
8016707 - 财政年份:2009
- 资助金额:
$ 45.61万 - 项目类别:
The Molecular Genetics and Cell Biology of Jaw Joint Morphogenesis
颌关节形态发生的分子遗传学和细胞生物学
- 批准号:
7790556 - 财政年份:2009
- 资助金额:
$ 45.61万 - 项目类别:
The Molecular Genetics and Cell Biology of Jaw Joint Morphogenesis
颌关节形态发生的分子遗传学和细胞生物学
- 批准号:
7546014 - 财政年份:2009
- 资助金额:
$ 45.61万 - 项目类别:
Imaging Delta-Induced Activation of Notch
成像 Delta 诱导的 Notch 激活
- 批准号:
7386757 - 财政年份:2007
- 资助金额:
$ 45.61万 - 项目类别:
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 45.61万 - 项目类别:
Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 45.61万 - 项目类别:
Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 45.61万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 45.61万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 45.61万 - 项目类别:
Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 45.61万 - 项目类别:
Discovery Early Career Researcher Award
RUI: Evaluation of Neurotrophic-Like properties of Spaetzle-Toll Signaling in the Developing and Adult Cricket CNS
RUI:评估发育中和成年蟋蟀中枢神经系统中 Spaetzle-Toll 信号传导的神经营养样特性
- 批准号:
2230829 - 财政年份:2023
- 资助金额:
$ 45.61万 - 项目类别:
Standard Grant
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 45.61万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 45.61万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 45.61万 - 项目类别:
Grant-in-Aid for Scientific Research (C)