A multifactorial pipeline to dissect combinatorial drug efficacy in Tuberculosis

剖析结核病组合药物疗效的多因素管道

基本信息

  • 批准号:
    10669196
  • 负责人:
  • 金额:
    $ 72.12万
  • 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:
    2021-08-09 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

ABSTRACT The rapid spread of multi-drug resistance has created a great need for new combination therapies to treat a variety of conditions, including infectious diseases and cancer. In one pressing example, multidrug resistant tuberculosis (TB) affects about 500,000 people each year and novel drug regimens are sorely needed. However, identifying new regimens has been daunting in part due to the inability to prioritize among a very large number of possible drug combinations. To address this need, we have generated an experimentally grounded, machine learning algorithm, INDIGO-MTB, which predicts the synergy or antagonism of TB drug combinations with high accuracy. Here we propose to adapt INDIGO-MTB into a multifactorial pipeline to dissect combinatorial drug efficacy and drive preclinical regimen development for TB. We will build in and validate the ability to predict drug interactions under stressful environmental conditions that mimic TB infection, and extract molecular mechanisms of drug interactions. We will then combine synergy and efficacy measurements to create new regimen rankings, which we will validate both in vitro and in a mouse model of TB infection. Altogether, our work will establish a tool for rapid assessment of TB drug combinations and a framework for applying this approach to other conditions where new multidrug therapies are needed.
摘要 多药耐药性的迅速蔓延,对新的联合用药产生了巨大的需求 治疗各种疾病的疗法,包括传染病和癌症。在一个 一个紧迫的例子是,耐多药结核病(TB)每年影响约50万人 迫切需要新的药物治疗方案。然而,确定新的治疗方案一直是 部分原因是无法在大量可能的药物中确定优先顺序, 组合。为了满足这一需求,我们已经产生了一个实验接地,机器 学习算法INDIGO-MTB,预测结核药物的协同作用或拮抗作用 组合精度高。在这里,我们建议将INDIGO-MTB调整为多因素 这是一个分析组合药物疗效和推动结核病临床前治疗方案开发的管道。 我们将建立并验证在压力环境下预测药物相互作用的能力。 模拟结核病感染的条件,并提取药物相互作用的分子机制。我们 然后将结合联合收割机协同作用和疗效测量,以创建新的方案排名, 我们将在体外和结核病感染的小鼠模型中进行验证。总之,我们的工作将 建立快速评估结核病药物组合的工具和应用框架 其他需要新的多药疗法的疾病。

项目成果

期刊论文数量(1)
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 }}

DAVID R SHERMAN其他文献

DAVID R SHERMAN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('DAVID R SHERMAN', 18)}}的其他基金

Drug tolerance, bacterial heterogeneity and adverse TB treatment outcomes
耐药性、细菌异质性和不良结核病治疗结果
  • 批准号:
    10665037
  • 财政年份:
    2021
  • 资助金额:
    $ 72.12万
  • 项目类别:
A multifactorial pipeline to dissect combinatorial drug efficacy in Tuberculosis
剖析结核病组合药物疗效的多因素管道
  • 批准号:
    10117593
  • 财政年份:
    2021
  • 资助金额:
    $ 72.12万
  • 项目类别:
Drug tolerance, bacterial heterogeneity and adverse TB treatment outcomes
药物耐受性、细菌异质性和不良结核病治疗结果
  • 批准号:
    10493290
  • 财政年份:
    2021
  • 资助金额:
    $ 72.12万
  • 项目类别:
A multifactorial pipeline to dissect combinatorial drug efficacy in Tuberculosis
剖析结核病组合药物疗效的多因素管道
  • 批准号:
    10465068
  • 财政年份:
    2021
  • 资助金额:
    $ 72.12万
  • 项目类别:
Drug tolerance, bacterial heterogeneity and adverse TB treatment outcomes
药物耐受性、细菌异质性和不良结核病治疗结果
  • 批准号:
    10271651
  • 财政年份:
    2021
  • 资助金额:
    $ 72.12万
  • 项目类别:
Drug tolerance, bacterial heterogeneity and adverse TB treatment outcomes
药物耐受性、细菌异质性和不良结核病治疗结果
  • 批准号:
    10907961
  • 财政年份:
    2021
  • 资助金额:
    $ 72.12万
  • 项目类别:
Project 2: Response to Treatment
项目 2:治疗反应
  • 批准号:
    10339374
  • 财政年份:
    2018
  • 资助金额:
    $ 72.12万
  • 项目类别:
Parallel Microscopic Determination of Fitness (PMDF) to Assess Growth and Viability of Mycobacterium tuberculosis
平行显微适应性测定 (PMDF) 评估结核分枝杆菌的生长和活力
  • 批准号:
    9089849
  • 财政年份:
    2015
  • 资助金额:
    $ 72.12万
  • 项目类别:
Bacterial Determinants of TB Progression
结核病进展的细菌决定因素
  • 批准号:
    8577274
  • 财政年份:
    2013
  • 资助金额:
    $ 72.12万
  • 项目类别:
Data Management and Resource Dissemination Core
数据管理和资源分发核心
  • 批准号:
    8577291
  • 财政年份:
    2013
  • 资助金额:
    $ 72.12万
  • 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:
    $ 72.12万
  • 项目类别:
    Fellowship
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:
    $ 72.12万
  • 项目类别:
    Continuing Grant
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:
    $ 72.12万
  • 项目类别:
    Research 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:
    $ 72.12万
  • 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:
    $ 72.12万
  • 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:
    $ 72.12万
  • 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:
    $ 72.12万
  • 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:
    $ 72.12万
  • 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:
    $ 72.12万
  • 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:
    $ 72.12万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了