Establishing an immune mechanome
建立免疫机制
基本信息
- 批准号:10713208
- 负责人:
- 金额:$ 39.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2028-08-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAnimal ModelAntigensArtificial IntelligenceBehaviorBiophysicsCell CommunicationCellsDiseaseDisease ProgressionEngineeringFutureGenerationsGenetically Engineered MouseImageImmuneImmune responseImmunocompetentImmunologicsImmunologyInflammatory ResponseKnowledgeLaboratoriesLengthMechanicsMediatingNational Institute of General Medical SciencesOrganPathologicPhenotypePhysiologicalResearchResearch PersonnelScienceSiteSystemTestingTissuesTransgenic OrganismsTranslational Researchcell behaviorcell motilitycellular engineeringhuman diseaseimmunogenicin vivoinsightmechanical forcemechanical propertiesmechanical signalmultiphoton microscopyprogramsresponsesingle-cell RNA sequencingtherapy resistanttooltraffickingwound
项目摘要
ABSTRACT
Mechanical forces are often modulated in diseased or wounded tissues as a result of inflammatory responses
driven by immune cell activity in the affected site(s). In fact, aberrant mechanical force generation in pathological
settings may mediate disease progression and treatment resistance. However, little is known about the response
of immune cells to these mechanical forces, particularly at the tissue-length scale, and even in normal
physiological settings. Thus there is a critically unmet need to fill overlooked gaps in our basic understanding of
the interplay between tissue-level mechanical forces and immune cell behavior, both collectively and at the
single-cell level. With the support of the NIGMS R35 MIRA for Early Stage Investigators over the next five years,
my laboratory will establish the first immune mechanome. We will investigate the impact of tissue mechanical
forces on the phenotype and function of innate and adaptive immune cells in a variety of organs. Leveraging
engineering-based tools and approaches, we will couple unbiased omics platforms to mechanical testing at
multiple scales (e.g., on cells in vivo, tissues ex vivo, and organs in vivo) in order to relate immune response to
mechanical forces. During multiscale compression, the trafficking, distribution, motility, cell-cell interactions, and
functional behavior of immune cells will be examined and perturbed via: i) intravital and dynamic imaging (e.g.,
with multiphoton microscopy of fluorescent cells or genetically engineered mouse models); ii) immunocompetent,
transgenic, and immunogenic animal models (e.g., OT-I/OT-II antigen systems); and iii) artificial intelligence-
based cell state analysis (e.g., from single cell RNA sequencing). We will also explore our hypothesis that
beneficial immune activity in the face of pathological conditions is suppressed by heightened tissue mechanical
forces. Importantly, the proposed Projects are to be performed in non-specific contexts that are independent of
tissue type, organ, or disease in order to maximize the potential for broad impact in the biomedical sciences.
The knowledge generated will lay the groundwork for future mechanistic and translational research in both
healthy and diseased settings. By operating at the interface of mechanical engineering and immunology in the
burgeoning field of “mechano-immunology,” my research program is uniquely suited to reveal new biophysical
insights and pathophysiological targets for human disease.
摘要
项目成果
期刊论文数量(0)
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Meenal Datta其他文献
Meenal Datta的其他文献
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{{ truncateString('Meenal Datta', 18)}}的其他基金
Targeting abnormal immunomechanics in the glioblastoma microenvironment to improve therapeutic response
针对胶质母细胞瘤微环境中的异常免疫力学以改善治疗反应
- 批准号:
10452571 - 财政年份:2021
- 资助金额:
$ 39.13万 - 项目类别:
Targeting abnormal immunomechanics in the glioblastoma microenvironment to improve therapeutic response
针对胶质母细胞瘤微环境中的异常免疫力学以改善治疗反应
- 批准号:
10187229 - 财政年份:2021
- 资助金额:
$ 39.13万 - 项目类别:
Targeting abnormal immunomechanics in the glioblastoma microenvironment to improve therapeutic response
针对胶质母细胞瘤微环境中的异常免疫力学以改善治疗反应
- 批准号:
10665616 - 财政年份:2021
- 资助金额:
$ 39.13万 - 项目类别:
TARGETING THE GRANULOMA MICROENVIRONMENT TO IMPROVE TUBERCULOSIS TREATMENT
针对肉芽肿微环境改善结核病治疗
- 批准号:
9048271 - 财政年份:2016
- 资助金额:
$ 39.13万 - 项目类别:
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