Engineering Native E. coli to Detect, Report, and Treat Colorectal Cancer
改造天然大肠杆菌来检测、报告和治疗结直肠癌
基本信息
- 批准号:10700076
- 负责人:
- 金额:$ 61.32万
- 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:2021-09-21 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAddressAffectAgeAnimal GeneticsAnimal ModelAttenuatedBacteriaBile AcidsBiological Response Modifier TherapyBiosensorBlack AmericanCancer BiologyCancer DetectionCancer EtiologyCaspaseCellsCessation of lifeColonColorectal CancerDataDevelopmentDiagnosisDiseaseDisease ProgressionEarly identificationEngineeringEngraftmentEnvironmentEscherichia coliFamilial Adenomatous Polyposis SyndromeGene ExpressionGenetic EngineeringGenetic ModelsGenetic Predisposition to DiseaseGoalsGrowthHealthIncidenceInflammatory Bowel DiseasesInterdisciplinary StudyInterventionKnowledgeMalignant NeoplasmsMethodsMicrofluidic MicrochipsMissionModelingMonitorMusOrganoidsOutcomePeptide HydrolasesPerformancePopulationPopulation DynamicsPreventionProgress ReportsProtease InhibitorProteinsProteomicsPublic HealthReporterReportingResearchResearch PersonnelRiskRoleScientistSignal TransductionSystemTestingTherapeuticTherapeutic AgentsTherapeutic UsesTimeTissuesVisualizationWorkadenomaanticancer researchcancer therapycolorectal cancer preventioncolorectal cancer progressioncolorectal cancer screeningcolorectal cancer treatmentdemographicsearly onset colorectal cancerepidemiology studygut microbiotahigh risk populationhost colonizationhost-microbe interactionsimprovedinnovationinterestmathematical modelmicrobial compositionmicrobiomemicroorganismnovelnovel strategiesorgan on a chippreventreceptorresponsesensorsynthetic biologytooltraittranslational impacttumortumor microenvironmenttumor progressionvector
项目摘要
PROJECT SUMMARY/ABSTRACT
Despite its overall decreasing occurrence, colorectal cancer (CRC) remains the fourth most common cause
of cancer deaths in the US. Unfortunately, epidemiological studies demonstrate an alarming increase in inci-
dence in populations below the age of 50, who are not routinely screened. Furthermore, CRC detection is difficult
in high-risk groups, including those with a genetic predisposition (e.g. familial adenomatous polyposis), disease
traits (e.g. inflammatory bowel disease), or from certain demographics (e.g. Black-Americans). Thus, there is a
significant need for the development of innovative solutions for the early detection of CRC and the prevention of
the transition from adenoma to CRC. To address this need, our interdisciplinary research team will develop
genetically engineered bacteria using synthetic biology approaches to identify early CRC development, monitor
and report changes in the adenoma and CRC microenvironment, and prevent cancer progression. To achieve
the above objectives, engineered bacteria have to engraft and colonize the hostile luminal environment, sense
and distinguish an abnormal environmental signal, compute this signal, and express a reporter or a therapeutic
agent. However, appropriate vectors with these features remain lacking, constraining synthetic biology applica-
tions for cancer research. Importantly, CRC is highly associated with E. coli, for which we have many synthetic
biology tools. Furthermore, our preliminary proof-of-concept studies have revealed that native E. coli can be
engineered to perpetually colonize fully conventional (i.e. non-microbiome depleted) hosts and to execute func-
tions of interest, e.g., deconjugation of luminal bile acids. Deconjugated bile acid and resultant farnesoid X re-
ceptor (FXR) agonism can suppress CRC development, indicating a potential therapeutic use of engineered
native bacteria. Building on our strong supportive preliminary results, we will identify native E. coli from healthy,
adenoma, and CRC tissues of a genetic model of CRC and engineer them to detect and treat CRC in response
to the cancer microenvironment. Furthermore, we will characterize the effects of different tumor environment
factors on the colonization and performances of engineered native E. coli in the colon organoid model in an
organ-on-chip with the support of mathematical modeling, thereby identifying specific CRC signals for program-
ming the responses of engineered native E. coli as CRC reporters and therapeutics. Finally, we will engineer
native bacteria to detect and attenuate the progression of CRC by quantitatively reporting the level of CRC-
related cysteine proteases and selectively inhibiting their activity. The research described in this proposal will
generate new, much-needed synthetic biology vectors that can be developed as biosensors and therapeutics of
adenoma and CRC, as well as many other diseases. Furthermore, this project will enrich our fundamental
knowledge about the CRC-microbiome relationship and elucidate the roles of cysteine proteases in CRC pro-
gression and treatment.
项目总结/文摘
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 }}
Amir Zarrinpar其他文献
Amir Zarrinpar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('Amir Zarrinpar', 18)}}的其他基金
Bacterial DNA as a Diagnostic Biomarker of Hepatocellular Carcinoma
细菌 DNA 作为肝细胞癌的诊断生物标志物
- 批准号:
10557105 - 财政年份:2022
- 资助金额:
$ 61.32万 - 项目类别:
The Role of Bile Salt Hydrolase in Glucose Metabolism
胆盐水解酶在葡萄糖代谢中的作用
- 批准号:
10365160 - 财政年份:2022
- 资助金额:
$ 61.32万 - 项目类别:
The Role of Bile Salt Hydrolase in Glucose Metabolism
胆盐水解酶在葡萄糖代谢中的作用
- 批准号:
10617180 - 财政年份:2022
- 资助金额:
$ 61.32万 - 项目类别:
Bacterial DNA as a Diagnostic Biomarker of Hepatocellular Carcinoma
细菌 DNA 作为肝细胞癌的诊断生物标志物
- 批准号:
10357369 - 财政年份:2022
- 资助金额:
$ 61.32万 - 项目类别:
Engineering Native E. coli to Detect, Report, and Treat Colorectal Cancer
改造天然大肠杆菌来检测、报告和治疗结直肠癌
- 批准号:
10330342 - 财政年份:2021
- 资助金额:
$ 61.32万 - 项目类别:
The Role of Altered Luminal Dynamics in OSA-Induced Atherosclerosis
管腔动力学改变在 OSA 诱发的动脉粥样硬化中的作用
- 批准号:
10273745 - 财政年份:2021
- 资助金额:
$ 61.32万 - 项目类别:
The Role of Altered Luminal Dynamics in OSA-Induced Atherosclerosis
管腔动力学改变在 OSA 诱发的动脉粥样硬化中的作用
- 批准号:
10455260 - 财政年份:2019
- 资助金额:
$ 61.32万 - 项目类别:
The Role of Altered Luminal Dynamics in OSA-Induced Atherosclerosis
管腔动力学改变在 OSA 诱发的动脉粥样硬化中的作用
- 批准号:
10217244 - 财政年份:2019
- 资助金额:
$ 61.32万 - 项目类别:
The Role of Altered Luminal Dynamics in OSA-Induced Atherosclerosis
管腔动力学改变在 OSA 诱发的动脉粥样硬化中的作用
- 批准号:
10884617 - 财政年份:2019
- 资助金额:
$ 61.32万 - 项目类别:
The Role of Altered Luminal Dynamics in OSA-Induced Atherosclerosis
管腔动力学改变在 OSA 诱发的动脉粥样硬化中的作用
- 批准号:
10456644 - 财政年份:2019
- 资助金额:
$ 61.32万 - 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:
$ 61.32万 - 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:
$ 61.32万 - 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:
$ 61.32万 - 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:
$ 61.32万 - 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:
$ 61.32万 - 项目类别:
Standard Grant
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:
$ 61.32万 - 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:
$ 61.32万 - 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:
$ 61.32万 - 项目类别:
EU-Funded
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:
$ 61.32万 - 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:
$ 61.32万 - 项目类别:
Research Grant