Effect of bacteriophages on cutaneous inflammation in acne

噬菌体对痤疮皮肤炎症的影响

基本信息

项目摘要

DESCRIPTION (provided by applicant): This proposal describes a 5-year training program for the development of an academic career in Dermatology, with a focus on furthering our understanding of how the cutaneous microbiome influences the immunobiology of the skin, using acne as a model. As principal investigator of this project, I am currently a postdoctoral researcher with training in microbiology, molecular biology, dermatology and immunology, all fields of study encompassed by this proposal, which is aimed at elucidating how Propionibacterium acnes bacteriophages can modulate the way in which this bacterium interacts with human cells in skin to trigger innate immune responses. My mentor on this project, who will oversee my career development, is Dr. Robert L. Modlin, a world-renowned immunologist and dermatologist at UCLA. Ongoing studies in his laboratory involve deciphering the mechanisms of host defense and innate immunity in skin, both of which are relevant to this proposal. Dr. Jenny Kim, who is also a dermatologist and professor at UCLA and a leading researcher in the study of the immunological basis of acne, will serve as my co-mentor. In the short-term, my objective is to elucidate how cutaneous bacteriophages can modulate the innate response to P. acnes in the context of both acne and healthy skin. My long-term career goal is to be an independent investigator in academic dermatology, and using the skin disease acne as a model, to develop a research program aimed at uncovering the mechanisms by which microorganisms interact with their hosts to trigger immune responses in the skin. Ultimately I hope to apply the insights gained from this research to develop improved therapeutics for the treatment of skin disease. This research proposal is based upon the hypothesis that the bacteriophage lysis, which involves degradation of cell wall components and the release of bacterial ligands, modulates the cutaneous innate immune response to P. acnes. In order to test this hypothesis I am proposing three specific aims. These include: 1) Elucidate innate pathways modulated by stimulation of monocytes with phage-killed P. acnes; 2) Investigate the mechanism through which bacteriophages alter P. acnes-induced immune responses according to specific effects on pattern recognition receptor activation pathways; and 3) Investigate how bacteriophage infection influences host immune responses at the site of disease. It is anticipated that the proposed studies will provide novel insights into the immunobiology of the skin, as through this work, we will define the mechanisms by which cutaneous bacteriophages can modulate innate responses, leading to the induction of distinct cytokine responses and functional outcomes that can influence acne pathogenesis. The investigation of the mechanisms by which bacteriophage lysis of a bacterial host modulates the cutaneous innate immune response is a novel area of exploration, and the studies outlined in this proposal have the potential to generate new insights into the role of bacteriophages in acne, the understanding of which will be critical for the ultimate goal of developing safe and effective phage-based acne therapies.
描述(由申请人提供):该提案描述了一个为期5年的培训计划,用于皮肤科学术生涯的发展,重点是进一步了解皮肤微生物组如何影响皮肤的免疫生物学,使用痤疮作为模型。作为该项目的主要研究者,我目前是一名博士后研究员,接受过微生物学,分子生物学,皮肤病学和免疫学的培训,该提案涵盖了所有研究领域,旨在阐明痤疮丙酸杆菌噬菌体如何调节这种细菌与皮肤中的人类细胞相互作用以触发先天免疫反应的方式。我在这个项目上的导师是罗伯特·L.博士,他将监督我的职业发展。莫德林是加州大学洛杉矶分校世界著名的免疫学家和皮肤科医生。他的实验室正在进行的研究涉及破译皮肤中宿主防御和先天免疫的机制,这两者都与这一提议有关。Jenny Kim博士也是加州大学洛杉矶分校的皮肤科医生和教授,也是痤疮免疫学基础研究的主要研究员,她将担任我的共同导师。在短期内,我的目标是阐明皮肤噬菌体如何调节痤疮和健康皮肤对痤疮丙酸杆菌的先天反应。我的长期职业目标是成为学术皮肤病学的独立研究者,并以皮肤病痤疮为模型,开发一个研究项目,旨在揭示微生物与宿主相互作用以引发皮肤免疫反应的机制。最终,我希望将从这项研究中获得的见解应用于开发治疗皮肤病的改进疗法。这项研究计划是基于这样的假设,即噬菌体裂解,其中涉及细胞壁成分的降解和细菌配体的释放,调节皮肤先天性免疫反应痤疮丙酸杆菌。为了验证这一假设,我提出了三个具体目标。其中包括:1)阐明通过用噬菌体杀死的痤疮丙酸杆菌刺激单核细胞调节的先天途径; 2)研究噬菌体根据对模式识别受体活化途径的特异性作用改变痤疮丙酸杆菌诱导的免疫应答的机制;和3)研究噬菌体感染如何影响疾病部位的宿主免疫应答。预计拟议的研究将为皮肤的免疫生物学提供新的见解,因为通过这项工作,我们将定义皮肤噬菌体可以调节先天反应的机制,从而诱导不同的细胞因子反应和功能结果,从而影响痤疮发病机制。研究噬菌体裂解细菌宿主调节皮肤先天免疫反应的机制是一个新的探索领域,本提案中概述的研究有可能对噬菌体在痤疮中的作用产生新的见解,了解这一点对于开发安全有效的基于噬菌体的痤疮疗法的最终目标至关重要。

项目成果

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Laura Jane Marinelli其他文献

Laura Jane Marinelli的其他文献

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{{ truncateString('Laura Jane Marinelli', 18)}}的其他基金

Effect of bacteriophages on cutaneous inflammation in acne
噬菌体对痤疮皮肤炎症的影响
  • 批准号:
    8750803
  • 财政年份:
    2014
  • 资助金额:
    $ 13.26万
  • 项目类别:
Effect of bacteriophages on cutaneous inflammation in acne
噬菌体对痤疮皮肤炎症的影响
  • 批准号:
    9116713
  • 财政年份:
    2014
  • 资助金额:
    $ 13.26万
  • 项目类别:
Effect of bacteriophages on cutaneous inflammation in acne
噬菌体对痤疮皮肤炎症的影响
  • 批准号:
    9330687
  • 财政年份:
    2014
  • 资助金额:
    $ 13.26万
  • 项目类别:
Characterization of the Lysogenic Pathway in P. acnes Bacteriophages
痤疮丙酸杆菌噬菌体溶原途径的表征
  • 批准号:
    8334125
  • 财政年份:
    2011
  • 资助金额:
    $ 13.26万
  • 项目类别:
Characterization of the Lysogenic Pathway in P. acnes Bacteriophages
痤疮丙酸杆菌噬菌体溶原途径的表征
  • 批准号:
    8526192
  • 财政年份:
    2011
  • 资助金额:
    $ 13.26万
  • 项目类别:
Characterization of the Lysogenic Pathway in P. acnes Bacteriophages
痤疮丙酸杆菌噬菌体溶原途径的表征
  • 批准号:
    8056677
  • 财政年份:
    2011
  • 资助金额:
    $ 13.26万
  • 项目类别:

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