Collaborative Research: NSF-ANR MCB/PHY: Probing Heterogeneity of Biological Systems by Force Spectroscopy

合作研究：NSF-ANR MCB/PHY：通过力谱探测生物系统的异质性

• 批准号: 2412550
• 负责人: Michael Hinczewski
• 金额: $ 29.91万
• 依托单位: Case Western Reserve University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-03-15 至 2027-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2412550&HistoricalAwards=false
• 关键词: Collaborative; Research; NSF; ANR; MCB

Biological molecules can exist in a number of different states, which influences how they function in the context of health and disease. Many of the current tools that we use to study these molecules measure average properties across states, hiding the underlying heterogeneity. This award will help decipher the nature of this heterogeneity through a combination of experiments and theory, including: 1) new methods of high-speed atomic force spectroscopy, which applies a rapidly increasing force on individual molecules (for example proteins, lipids, or complexes of bound molecules) to unravel or break them; 2) machine learning and other data analysis techniques that can extract information from the experimental results, in order to characterize the original states of the molecules and their dynamics; 3) analyzing heterogeneity of molecules in living cells, particularly the adhesion complexes that bind cells together.To accomplish this, the project brings together a multidisciplinary consortium of biophysicists and engineers.Broader impacts of the project will lead to the development of next generation tools for atomic force microscopy, with potential applications to other nanotechnology platforms like optical tweezers. The theory and data analysis methods will be generally applicable to any biological system, as well as in soft matter and materials science. The expected results will be relevant for a variety of health-related biological processes, from immune recognition during infection to pathologies involving protein aggregation, present in many neurological disorders. In education, the project will foster the scientific formation of young researchers through internships, summer schools, and opportunities for outreach to the broader community. This collaborative US/France project is supported by the US National Science Foundation (NSF) and the French Agence Nationale de la Recherche (ANR), where NSF funds the US investigators and ANR funds the partners in France. The US investigators are jointly funded by the Physics of Living Systems program in the Directorate for Mathematical and Physical Sciences and the Molecular Biophysics program/Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences.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.

生物分子可以存在于许多不同的状态中，从而影响它们在健康和疾病背景下的功能。我们用于研究这些分子的许多当前工具测量了整个州的平均特性，从而隐藏了潜在的异质性。该奖项将通过实验和理论的组合有助于解读这种异质性的性质，包括：1）高速原子力光谱的新方法，该方法对单个分子（例如蛋白质，脂质，脂质，或结合分子的络合物）施加了快速增加的力来解开或破解它们； 2）机器学习和其他数据分析技术，可以从实验结果中提取信息，以表征分子的原始状态及其动力学； 3）分析生物细胞中分子的异质性，尤其是将细胞结合在一起的粘附复合物。为了实现这一目标，该项目汇集了一个生物物理学家和工程师的多学科联盟。该项目的影响将导致下一代力显微镜的开发，例如其他Nanotechnologe tweez的下一代工具的开发。理论和数据分析方法通常适用于任何生物系统以及软物质和材料科学。预期的结果将与各种与健康相关的生物学过程有关，从感染期间的免疫识别到许多神经系统疾病中涉及蛋白质聚集的病理学。在教育方面，该项目将通过实习，暑期学校和向更广泛的社区推广的机会来促进年轻研究人员的科学形成。美国国家科学基金会（NSF）和法国Agence Nationale de la Recherche（ANR）的支持，NSF为美国调查人员和ANR提供了法国合作伙伴的资助。 The US investigators are jointly funded by the Physics of Living Systems program in the Directorate for Mathematical and Physical Sciences and the Molecular Biophysics program/Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences.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.