CAREER: Measuring and Modeling Non-canonical Wnt Signaling in Regulation of Cell State

职业:细胞状态调节中的非规范 Wnt 信号传导的测量和建模

基本信息

  • 批准号:
    2047289
  • 负责人:
  • 金额:
    $ 124.51万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-03-01 至 2026-02-28
  • 项目状态:
    未结题

项目摘要

This project aims to provide insights into cell-to-cell communication that play a crucial role in forming tissues and organs and the organization of different body parts during embryonic development. How cells communicate and govern these fundamental biological processes are highly complex and dynamic, and their behavior is very difficult to predict from knowledge of the individual parts. Therefore, the question arises how we should analyze and understand such complexity and which measurement technologies will prove most useful. Recently, several high-throughput approaches for collecting large-scale datasets, particularly those involving gene expression, have unlocked the door to data-driven systems biology-based projects. However, studying many interactions, even in a closely interconnected network, is powerful, but it is often hard to see the forest for the trees. Most often, system biologists rely on mathematical and computational models to analyze large-scale datasets and use these models to make scientific breakthroughs. To inspire and train the next generation of scientists in both experimental and computational approaches, this project will provide an opportunity for undergraduate students from diverse backgrounds to learn both cutting-edge cell biology-based experimentation and computational methods for formulating, simplifying, and extracting critical information from large-scale quantitative experimental data. A combination of hands-on training and lesson plans on the concept of 'cellular decision-making' for high school teachers will further promote data-driven biology among high school students. The graduate students and postdoctoral fellows working on this project will integrate experimental and mathematical modeling techniques that can be applied to broad areas of biology. This quantitative research theme will be carried forward by mentorship to high school students and through public engagement activities with the local community. The epithelial-mesenchymal transition (EMT) is a central mechanism for diversifying the cells found in complex tissues. During EMT, epithelial cells adopt mesenchymal properties by altering their morphology, cellular architecture, adhesion, and migratory capacity. Several growth factors, including TGF-beta and Wnt, have been shown to trigger the EMT in both embryonic development as well as normal and transformed cells. However, a mechanistic and integrated understanding of how these various factors cooperate to induce the EMT in epithelial cells or transdifferentiation in fibroblast is still lacking. The goal of this project is to develop an integrated understanding of how Wnt and TGF-beta pathways control fundamental cell biological and developmental processes of EMT and cell migration. The research project will reveal mechanistic insights into how Wnt signaling drives EMT and promotes cell migration, and determine whether cooperation between Wnt and TGF-beta signaling is necessary for EMT. The project will also provide a biochemical portrait to determine how proteins in the Wnt pathway interact and interconnect with TGF-beta signaling and determine how these connections change as epithelial cells undergo transdifferentiation.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.
该项目旨在提供对细胞间通讯的见解,这种通讯在胚胎发育期间形成组织和器官以及组织不同身体部位方面发挥着至关重要的作用。细胞如何交流和控制这些基本的生物过程是非常复杂和动态的,而且它们的行为很难根据对各个部分的了解来预测。因此,问题出现了,我们应该如何分析和理解这种复杂性,以及哪些测量技术将被证明是最有用的。最近,几种用于收集大规模数据集的高通量方法,特别是那些涉及基因表达的方法,打开了基于数据驱动的系统生物学项目的大门。然而,研究许多相互作用,即使是在一个紧密相连的网络中,也是强大的,但往往很难只见树木不见森林。最常见的情况是,系统生物学家依靠数学和计算模型来分析大规模数据集,并使用这些模型来取得科学突破。为了激励和培训实验和计算方法方面的下一代科学家,这个项目将为来自不同背景的本科生提供机会,学习基于细胞生物学的尖端实验和计算方法,用于制定、简化和从大规模定量实验数据中提取关键信息。为高中教师提供的实践培训和关于“细胞决策”概念的课程计划将进一步在高中生中推广数据驱动的生物学。从事这个项目的研究生和博士后研究员将整合实验和数学建模技术,这些技术可以应用于生物学的广泛领域。这一量化研究主题将通过对高中生的辅导和与当地社区的公共参与活动来弘扬。上皮-间充质转化(EMT)是复杂组织中细胞多样化的核心机制。在EMT过程中,上皮细胞通过改变其形态、细胞结构、黏附和迁移能力而具有间充质特性。一些生长因子,包括转化生长因子-β和Wnt,已经被证明在胚胎发育以及正常和转化的细胞中都能触发EMT。然而,对于这些不同因素如何协同诱导上皮细胞的EMT或成纤维细胞的转分化,目前还缺乏一个完整的机制和了解。这个项目的目标是对WNT和转化生长因子-β通路如何控制EMT和细胞迁移的基本细胞生物学和发育过程有一个完整的理解。该研究项目将揭示Wnt信号如何驱动EMT和促进细胞迁移的机制,并确定Wnt和转化生长因子-β信号之间的合作是否对EMT是必要的。该项目还将提供一个生化画像,以确定Wnt途径中的蛋白质如何与转化生长因子-β信号相互作用和互连,并确定这些连接在上皮细胞经历转分化时如何变化。该奖项反映了NSF的法定使命,并通过使用基金会的智力优势和更广泛的影响审查标准进行评估,被认为值得支持。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Taran Gujral其他文献

Acalabrutinib in Combination with Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory B-Cell Lymphoma: A Phase I/II Study of Safety, Efficacy and Immune Correlative Analysis
  • DOI:
    10.1182/blood-2023-183034
  • 发表时间:
    2023-11-02
  • 期刊:
  • 影响因子:
  • 作者:
    Christina Poh;Victor A Chow;Ryan C Lynch;Chaitra S Ujjani;Mazyar Shadman;Brian G Till;Vikram Raghunathan;Edus H Warren;Jordan Gauthier;Stephen D Smith;Taran Gujral;Chihiro Morishima;Qian Wu;Jenna M Voutsinas;Amy Sperling;Joshua Dizon;David G Maloney;Ajay K Gopal
  • 通讯作者:
    Ajay K Gopal

Taran Gujral的其他文献

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