Circadian rhythms and alcohol in the BMAL1 knockout rat
BMAL1 敲除大鼠的昼夜节律和酒精
基本信息
- 批准号:10451307
- 负责人:
- 金额:$ 21.35万
- 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:2022-09-20 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:ARNTL geneAddressAlcohol consumptionAlcohol dependenceAlcoholic Liver DiseasesAlcoholsAnimal ModelAnimalsBioenergeticsBiological ProcessBrain InjuriesCRISPR/Cas technologyCause of DeathCell physiologyCellsChronotherapyCircadian DysregulationCircadian RhythmsClinicalComplexDepressed moodDevelopmentDiseaseDoseEnsureEnvironmental Risk FactorEthanol toxicityEtiologyExhibitsFeedbackFetal Alcohol SyndromeFunctional disorderGastrointestinal DiseasesGenesGeneticGenetic TranscriptionGenotypeGoalsHealthHeart DiseasesHepaticHistopathologyHumanImmune System DiseasesImpairmentInflammatoryInjuryIntestinal permeabilityKidney DiseasesKnock-outKnowledgeLiverLiver MitochondriaLiver diseasesMalignant NeoplasmsMedicalMental HealthMessenger RNAMetabolicMetabolismMethodsMitochondriaMitochondrial DNAModelingMolecularMolecular TargetMusNormal tissue morphologyNutrientOrganOutcomeOutcomes ResearchOutputPathologicPathologyPathway interactionsPatientsPhysiologicalPhysiologyProductionPublishingRattusReactive Oxygen SpeciesResearchResearch PersonnelResearch Project GrantsResolutionRespirationRespiratory physiologyRestRiskRisk FactorsRoleStimulusStressSystemTechnologyTestingTimeTissuesTranscriptTranscription CoactivatorTranscriptional RegulationUlcerUnited StatesVariantWorkalcohol riskbasechronic alcohol ingestioncircadiancircadian biologyclinically relevantdrug developmenteffective therapyexperimental studygenome editingglycogen metabolismhigh rewardknockout genelipid metabolismliver functionliver injuryliver metabolismmetabolomicsmolecular clocknoveloxidative damagepre-clinicalpreclinical studypreventable deathproblem drinkerrespiratorytissue injurytranslational impact
项目摘要
PROJECT SUMMARY
Liver disease is the number one cause of death from long-term heavy alcohol drinking in the United States. While
dose and duration of alcohol consumption are well-accepted risk factors for disease, it is clear that the etiology
of alcohol-related liver disease (ALD) is highly complex, involving many still unknown genetic, metabolic, and
environmental factors. This complexity also likely explains why there are so few effective therapies for treating
ALD. Therefore, a major unanswered question for the alcohol field is – what additional environmental factors,
metabolic impairments, and/or molecular disturbances are required for liver pathology to occur in the alcohol
consumer? A vital temporal integrator of environmental stimuli, metabolism, and cellular transcriptional control
is the circadian system. At the cellular level, 24-h circadian rhythms are driven by a transcriptional-translational
feedback loop system. This molecular clock mechanism involves activation of core clock genes and many
downstream clock-output genes by the transcriptional activators BMAL1 and CLOCK. This molecular clock
mechanism ensures that specific cellular and biological processes occur at the correct time of day. Accumulating
evidence shows that circadian rhythm disruption worsens tissue function and injury in animals and humans
consuming alcohol. Despite these new findings, the mechanistic understanding of how this occurs is very limited.
This current proposal addresses a critical target of alcohol toxicity – the mitochondrion. Even though multiple
studies have shown that alcohol severely impairs mitochondrial function, there have not been rigorous studies
examining the impact of circadian disruption on temporal control of hepatic mitochondrial function in the alcohol
consumer. We hypothesize that circadian disruption worsens alcohol-related impairments in hepatic
mitochondrial bioenergetic function and increases tissue injury. To test this hypothesis, we will use an exciting
new animal model, the Bmal1 knockout rat – the first rat model of a global clock gene knockout developed with
CRISPR/Cas9 genome editing technology. In Aim 1, we will determine the role of Bmal1 in the temporal control
of 24-h physiologic, metabolic, and molecular rhythms in alcohol-fed rats. In Aim 2, we will determine the role
Bmal1 in alcohol-related mitochondrial bioenergetic dysfunction and liver injury. Successful completion of these
studies will provide novel information regarding the interaction of the circadian system and alcohol on tissue and
mitochondrial function and pathology. The knowledge gained from this work also has the ability to influence
multiple scientific fields and facilitate development of novel chronotherapy-based approaches for treating patients
suffering from ALD and other related liver diseases.
项目总结
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 }}
SHANNON MARIE BAILEY其他文献
SHANNON MARIE BAILEY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('SHANNON MARIE BAILEY', 18)}}的其他基金
Circadian and mitochondrial dysfunction in alcohol-related liver disease
酒精相关性肝病中的昼夜节律和线粒体功能障碍
- 批准号:
10667861 - 财政年份:2023
- 资助金额:
$ 21.35万 - 项目类别:
Circadian rhythms and alcohol in the BMAL1 knockout rat
BMAL1 敲除大鼠的昼夜节律和酒精
- 批准号:
10707005 - 财政年份:2022
- 资助金额:
$ 21.35万 - 项目类别:
Molecular circadian clocks and alcohol-induced liver injury
分子生物钟和酒精性肝损伤
- 批准号:
9759734 - 财政年份:2018
- 资助金额:
$ 21.35万 - 项目类别:
Alcohol-Induced Mitochondrial Dysfunction and the Hepatocyte Clock
酒精引起的线粒体功能障碍和肝细胞时钟
- 批准号:
9280738 - 财政年份:2016
- 资助金额:
$ 21.35万 - 项目类别:
Hepatocyte Clock and Alcoholic Fatty Liver Injury
肝细胞时钟与酒精性脂肪肝损伤
- 批准号:
8144478 - 财政年份:2010
- 资助金额:
$ 21.35万 - 项目类别:
Hepatocyte Clock and Alcoholic Fatty Liver Injury
肝细胞时钟与酒精性脂肪肝损伤
- 批准号:
8065283 - 财政年份:2010
- 资助金额:
$ 21.35万 - 项目类别:
Alcoholic Liver Dysfunction Potentiation by Hyperlipidemia and Cigarette Smoke
高脂血症和吸烟加剧酒精性肝功能障碍
- 批准号:
8316433 - 财政年份:2009
- 资助金额:
$ 21.35万 - 项目类别:
Alcoholic Liver Dysfunction Potentiation by Hyperlipidemia and Cigarette Smoke
高脂血症和吸烟加剧酒精性肝功能障碍
- 批准号:
7932863 - 财政年份:2009
- 资助金额:
$ 21.35万 - 项目类别:
Alcoholic Liver Dysfunction Potentiation by Hyperlipidemia and Cigarette Smoke
高脂血症和吸烟加剧酒精性肝功能障碍
- 批准号:
7798912 - 财政年份:2009
- 资助金额:
$ 21.35万 - 项目类别:
Alcoholic Liver Dysfunction Potentiation by Hyperlipidemia and Cigarette Smoke
高脂血症和吸烟加剧酒精性肝功能障碍
- 批准号:
8127680 - 财政年份:2009
- 资助金额:
$ 21.35万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 21.35万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 21.35万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 21.35万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 21.35万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 21.35万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 21.35万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 21.35万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 21.35万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 21.35万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 21.35万 - 项目类别:
Research Grant