CAREER: Elucidating structure-function relationships of inflammasome-activating nanomaterials

职业:阐明炎症体激活纳米材料的结构-功能关系

基本信息

  • 批准号:
    2142917
  • 负责人:
  • 金额:
    $ 63.74万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-04-01 至 2027-03-31
  • 项目状态:
    未结题

项目摘要

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).NON-TECHNICAL ABSTRACT:This CAREER award proposes to develop polymeric nanomaterials and investigate their effects on immune cell functions, specifically, activation of the inflammasome, a multiprotein complex that controls immune cell functions during normal and pathological (leading to disease) processes. By varying the self-assembly of their polymeric building blocks, the proposed set of nanomaterials will activate different inflammasome functions, and will be used as tools to evaluate how their surface and core chemical patterns influence uptake, intracellular fate, and inflammasome activation in immune cells. The results from the proposed studies will generate a set of new guidelines that will provide clear criteria for the design of novel nanomaterials that elicit predictable degrees of inflammasome activation and can be used for biological applications, including immunotherapy and vaccines. The project’s educational goals are to integrate the proposed research modules into several educational programs developed for students at various educational levels spanning the K-12, college, and graduate levels and increase the participation of students from underrepresented groups in bioengineering research. These efforts include the integration of mentorship and research experiences into immuno-engineering and bioengineering courses to provide a unique learning experience to a diverse workforce at the emerging interface of chemical engineering, biomaterials, and immunology, a summer workshop for local K-12 students from underrepresented groups, new research experiences for women and underrepresented students to encourage and promote the involvement of these students in the field of bioengineering, recruiting graduate students from underrepresented groups and an online open course network of teachers and students interested in immunoengineering to disseminate, discuss, and collaborate. TECHNICAL ABSTRACT:The goals of this CAREER proposal are to establish strong and integrated research and educational program that: (1) provides a foundational understanding of how different nanomaterials interact with immune cells resulting in inflammasome activation, (2) advances the field of inflammasome-activating nanomaterials for biological applications including targeting inflammatory diseases and (3) encourages and inspires a diverse set of K-12 students, undergraduate and graduate students to participate in learning and contributing to the bioengineering field. This proposal will develop a library of polymeric supramolecular nanoparticles with different surface and core properties to elucidate the effects of nanomaterial properties on inflammasome activation and identify the underlying molecular mechanisms. Specifically, supramolecular polymeric nanomaterials with tunable surface and core properties will be developed to determine how they influence uptake, intracellular fate, and inflammasome activation in various immune cells. The mechanisms underlying inflammasome activation in response to various nanomaterials will be dissected by assessing key components of lysosomal disruption–cathepsin B maturation and calcium influx-mitochondrial dysfunction pathways. The PI’s long-term educational goal is to mentor and train the diverse cadre of students from pre-college (K-12), undergraduate and graduate levels as the next generation of bioengineers to become critical thinkers capable of contributing to society and the growing body of scientific knowledge either through academic, industrial or entrepreneurial route. Towards that goal, the educational aims for this project include: (1) integration of mentorship and research experiences into the educational curriculum, including project-based biology for engineers course and a lab-based immunoengineering course; (2) to encourage and promote the involvement of K-12 students from underrepresented groups in the bioengineering field by leveraging current efforts in organizing summer workshops that provide hands-on training and graduate students run ‘Science Day’ that will include various activities such as students presentations, science trivia and team-based competition; (3) designing and developing an online resource for sharing immunoengineering course materials to instructors and graduate students. (4) to increase awareness about how engineers can contribute to the biology and immunology field to advance human health by disseminating outcomes of our research to broader communities, including the research community and the general population. The proposed research will generate a set of new guidelines that will provide clear criteria for structural and functional requirements to design the next generation of novel nanomaterials that elicit predictable degrees of inflammasome activation and can be used for various biological applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
该奖项全部或部分由2021年美国救援计划法案(公法117-2)资助。非技术摘要:该职业奖旨在开发聚合物纳米材料并研究其对免疫细胞功能的影响,特别是炎症体的激活,炎症体是一种多蛋白复合物,在正常和病理过程中控制免疫细胞功能(导致疾病)。通过改变其聚合物构建块的自组装,所提出的一组纳米材料将激活不同的炎性体功能,并将用作评估其表面和核心化学模式如何影响免疫细胞中的摄取、细胞内命运和炎性体激活的工具。拟议研究的结果将产生一套新的指导方针,为设计新型纳米材料提供明确的标准,这些纳米材料可引起可预测程度的炎性小体激活,并可用于生物学应用,包括免疫治疗和疫苗。该项目的教育目标是将拟议的研究模块整合到为K-12、大学和研究生等不同教育水平的学生开发的几个教育项目中,并增加来自代表性不足群体的学生在生物工程研究中的参与。这些努力包括将导师和研究经验整合到免疫工程和生物工程课程中,为化学工程,生物材料和免疫学的新兴界面的多样化劳动力提供独特的学习体验,为来自代表性不足的群体的当地K-12学生举办夏季研讨会,为妇女和代表性不足的学生提供新的研究经验,以鼓励和促进这些学生参与生物工程领域,从代表性不足的群体中招募研究生,并建立一个由对免疫工程感兴趣的教师和学生组成的在线开放课程网络,以传播、讨论和合作。技术摘要:本职业建议的目标是建立强大的综合研究和教育计划,以:(1)提供了对不同纳米材料如何与免疫细胞相互作用导致炎性小体活化的基本理解,(2)推进炎性小体活化纳米材料的生物应用领域,包括靶向炎性疾病和(3)鼓励和激励各种K-12学生,本科生和研究生参与学习,并为生物工程领域做出贡献。该提案将开发具有不同表面和核心性质的聚合物超分子纳米颗粒库,以阐明纳米材料性质对炎性小体激活的影响并确定潜在的分子机制。具体而言,将开发具有可调表面和核心特性的超分子聚合物纳米材料,以确定它们如何影响各种免疫细胞的摄取、细胞内命运和炎性体活化。将通过评估溶酶体破坏-组织蛋白酶B成熟和钙流入-线粒体功能障碍途径的关键组分来剖析炎症体激活对各种纳米材料的反应的潜在机制。PI的长期教育目标是指导和培训来自大学预科(K-12),本科和研究生水平的学生作为下一代生物工程师,成为能够通过学术,工业或创业路线为社会和不断增长的科学知识做出贡献的批判性思想家。为此,本项目的教育目标包括:(1)将导师制和研究经验融入教育课程,包括基于项目的工程师生物学课程和基于实验室的免疫工程课程;(2)鼓励和促进来自生物工程领域代表性不足群体的K-12学生参与,利用目前的努力,组织暑期讲习班,在培训和研究生运行“科学日”,将包括各种活动,如学生演讲,科学琐事和团队为基础的竞争;(3)设计和开发一个在线资源,分享免疫工程课程材料的教师和研究生。(4)提高人们对工程师如何为生物学和免疫学领域做出贡献的认识,通过将我们的研究成果传播给更广泛的社区,包括研究界和普通人群,来促进人类健康。这项研究将产生一套新的指导方针,为设计下一代新型纳米材料的结构和功能要求提供明确的标准,这些纳米材料可引起可预测程度的炎性体激活,并可用于各种生物学应用。该奖项反映了NSF的法定使命,并被认为值得通过使用基金会的智力价值和更广泛的影响审查进行评估来支持的搜索.

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Nanoparticle-mediated co-delivery of inflammasome inhibitors provides protection against sepsis
  • DOI:
    10.1039/d3nr05570a
  • 发表时间:
    2024-01-10
  • 期刊:
  • 影响因子:
    6.7
  • 作者:
    Nandi,Dipika;Debnath,Maharshi;Kulkarni,Ashish
  • 通讯作者:
    Kulkarni,Ashish
Protein Corona Formation on Lipid Nanoparticles Negatively Affects the NLRP3 Inflammasome Activation
  • DOI:
    10.1021/acs.bioconjchem.3c00329
  • 发表时间:
    2023-09-14
  • 期刊:
  • 影响因子:
    4.7
  • 作者:
    Debnath,Maharshi;Forster,James;Kulkarni,Ashish
  • 通讯作者:
    Kulkarni,Ashish
mRNA-carrying lipid nanoparticles that induce lysosomal rupture activate NLRP3 inflammasome and reduce mRNA transfection efficiency
  • DOI:
    10.1039/d2bm00883a
  • 发表时间:
    2022-08-09
  • 期刊:
  • 影响因子:
    6.6
  • 作者:
    Forster, James, III;Nandi, Dipika;Kulkarni, Ashish
  • 通讯作者:
    Kulkarni, Ashish
Effect of mRNA-Carrying Lipid Nanoparticle Composition on NLRP3 Inflammasome Activation and mRNA Transfection Efficiency
携带mRNA的脂质纳米颗粒组合物对NLRP3炎性体激活和mRNA转染效率的影响
  • DOI:
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    0
  • 作者:
    James Forster, Ashish Kulkarni
  • 通讯作者:
    James Forster, Ashish Kulkarni
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Ashish Kulkarni其他文献

Final Report : Team 2 Predicting Golden Globe Awards & Christmas Day Movie Gross
最终报告:Team 2 预测金球奖
  • DOI:
  • 发表时间:
    2014
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Deepak Balasubramaniam;Justin H. C. Chan;Ashish Kulkarni;Dandan Zheng
  • 通讯作者:
    Dandan Zheng
MFBE: Leveraging Multi-Field Information of FAQs for Efficient Dense Retrieval
MFBE:利用常见问题解答的多字段信息进行高效密集检索
  • DOI:
    10.1007/978-3-031-33380-4_9
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Debopriyo Banerjee;Mausam Jain;Ashish Kulkarni
  • 通讯作者:
    Ashish Kulkarni
Solvent Engineering to Enhance the Performance of Silver-Bismuth Halide Material for Lead-Free Perovskite Solar Cells
溶剂工程提高无铅钙钛矿太阳能电池用银铋卤化物材料的性能
  • DOI:
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Ashish Kulkarni;Masashi Ikegami;Tsutomu Miyasaka
  • 通讯作者:
    Tsutomu Miyasaka
Optimizing Bidirectional EV Charger with Rapid Charging Architecture using Fuzzy Logic Control
使用模糊逻辑控制优化具有快速充电架构的双向电动汽车充电器
Morphology evolution of non-toxic MA3Bi2I9 based lead- free perovskite solar cells
无毒MA3Bi2I9基无铅钙钛矿太阳能电池的形貌演化

Ashish Kulkarni的其他文献

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