Chemical Biological Discovery of Lipid Virulence Factors in the Major Bacterial Pathogens

主要细菌病原体中脂质毒力因子的化学生物学发现

基本信息

  • 批准号:
    10651853
  • 负责人:
  • 金额:
    $ 62.28万
  • 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:
    2022-06-22 至 2027-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary Chemical Biological Discovery of Lipid Virulence Factors in the Major Bacterial Pathogens For decades, the search for the causes of bacterial virulence has focused on genes rather than metabolites. Genetic approaches have been broadly successful, and modern infectious disease research relies fundamentally on genomic maps of the major pathogens. Owing to the lack of whole-organism chemical biology tools, bacterial lipids have not been systematically tested for their roles in virulence, even though lipids are the primary interface with the human host, where they control nutrient flow and trigger host immune response. We invented a mass spectrometry platform for lipid profiling to detect nearly all ionizable lipids in a bacterial cell within 2 hours. Experiments on Mycobacterium tuberculosis and Salmonella enterica serovar Typhi now provide clear evidence for the general insight that many, perhaps the majority, of lipids in the world's bacterial pathogens, are currently unknown as named compounds. Based on successes in identifying virulence factors in two major pathogens of worldwide significance, we will carry out a chemical biology approach known as forward lipidomics. Specifically, we will use whole organism mass spectrometry profiling to discover the lipids that are selectively expressed in virulent bacteria and are unknown in existing lipid catalogs. Then, we will chemically synthesize the virulence associated lipids and link them to their biosynthetic genes for deletion in bacteria using reverse genetic approaches. Using genetically modified bacteria that are deficient in defined lipids, we will determine the roles of virulence lipids during infection. Using nature identical synthetic lipids, we will determine the cellular mechanisms of generation of foamy macrophages and identify immune receptors that mediate host response. We will create lipid maps of the major Gram negative pathogen groups based on patient strains to build the overlooked field of chemical biology of bacterial virulence. These basic and translational studies will support the development new forward lipidomics approaches to the diagnosis and treatment of major infectious diseases.
项目摘要 主要病原菌脂质毒力因子的化学生物学发现 几十年来,对细菌毒性原因的研究一直集中在基因而不是代谢物上。 遗传学方法已经取得了广泛的成功,现代传染病研究依赖于 主要病原体的基因组图谱。由于缺乏全有机化学物质, 生物学工具,细菌脂质还没有系统地测试它们在毒力中的作用,即使脂质 是与人类宿主的主要界面,在那里它们控制营养流并触发宿主免疫 反应我们发明了一种用于脂质谱分析的质谱平台,以检测几乎所有的可电离脂质。 细菌细胞在2小时内。结核分枝杆菌和肠道沙门氏菌血清型的实验研究 伤寒现在提供了明确的证据,为一般的见解,许多,也许是大多数,脂质在世界上的 细菌病原体,是目前未知的命名化合物。基于在确定毒力方面的成功 因子在两个主要病原体的世界性意义,我们将进行化学生物学方法已知 as forward向前lipidomics脂质组学.具体来说,我们将使用整个生物体质谱分析来发现 在毒性细菌中选择性表达的脂质,在现有的脂质目录中是未知的。然后我们 将化学合成与毒性相关的脂质,并将其与其生物合成基因连接以进行删除 在细菌中使用反向遗传方法。使用基因改造的细菌, 脂质,我们将确定毒力脂质在感染过程中的作用。使用天然相同的合成脂质,我们 将确定泡沫巨噬细胞产生的细胞机制并识别免疫受体 介导宿主反应。我们将根据以下内容创建主要革兰氏阴性病原体组的脂质图谱: 病人菌株建立被忽视的化学生物学领域的细菌毒力。这些基本和 翻译研究将支持开发新的前向脂质组学方法来诊断和 重大传染病的治疗。

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)
Nucleocapsid protein accumulates in renal tubular epithelium of a post-COVID-19 patient.
  • DOI:
    10.1128/spectrum.03029-23
  • 发表时间:
    2023-12-12
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
  • 通讯作者:
{{ 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 Branch MOODY其他文献

DAVID Branch MOODY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 Branch MOODY', 18)}}的其他基金

Chemical Biological Discovery of Lipid Virulence Factors in the Major Bacterial Pathogens
主要细菌病原体中脂质毒力因子的化学生物学发现
  • 批准号:
    10518252
  • 财政年份:
    2022
  • 资助金额:
    $ 62.28万
  • 项目类别:
Profiling and Mapping Core
分析和映射核心
  • 批准号:
    10612026
  • 财政年份:
    2021
  • 资助金额:
    $ 62.28万
  • 项目类别:
Study of M. tuberculosis under human host selection to identify virulence and barrier lipids (Project 1)
研究人类宿主选择下的结核分枝杆菌以确定毒力和屏障脂质(项目 1)
  • 批准号:
    10612035
  • 财政年份:
    2021
  • 资助金额:
    $ 62.28万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10271479
  • 财政年份:
    2021
  • 资助金额:
    $ 62.28万
  • 项目类别:
Metabolic adaptions of Mycobacterium tuberculosis at diverse host-pathogen interfaces
结核分枝杆菌在不同宿主-病原体界面的代谢适应
  • 批准号:
    10630740
  • 财政年份:
    2021
  • 资助金额:
    $ 62.28万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10612024
  • 财政年份:
    2021
  • 资助金额:
    $ 62.28万
  • 项目类别:
Profiling and Mapping Core
分析和映射核心
  • 批准号:
    10271480
  • 财政年份:
    2021
  • 资助金额:
    $ 62.28万
  • 项目类别:
Profiling and Mapping Core
分析和映射核心
  • 批准号:
    10438913
  • 财政年份:
    2021
  • 资助金额:
    $ 62.28万
  • 项目类别:
Metabolic determinants of Mtb virulence, vulnerability and variation
结核分枝杆菌毒力、脆弱性和变异的代谢决定因素
  • 批准号:
    10438911
  • 财政年份:
    2021
  • 资助金额:
    $ 62.28万
  • 项目类别:
Metabolic determinants of Mtb virulence, vulnerability and variation
结核分枝杆菌毒力、脆弱性和变异的代谢决定因素
  • 批准号:
    10612023
  • 财政年份:
    2021
  • 资助金额:
    $ 62.28万
  • 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:
    $ 62.28万
  • 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:
    $ 62.28万
  • 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:
    $ 62.28万
  • 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:
    $ 62.28万
  • 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:
    $ 62.28万
  • 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:
    $ 62.28万
  • 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:
    $ 62.28万
  • 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:
    $ 62.28万
  • 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:
    $ 62.28万
  • 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:
    $ 62.28万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了