BRITE Fellow: Systems-level Mechanobiology from the Cellular Mechanome to Sustainable Meat Production

BRITE 研究员：从细胞机械组到可持续肉类生产的系统级机械生物学

• 批准号: 2135747
• 负责人: Amy Rowat
• 金额: $ 99.55万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2027-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2135747&HistoricalAwards=false
• 关键词: BRITE; Fellow; Systems; level; Mechanobiology

This Boosting Research Ideas for Transformative and Equitable Advances in Engineering (BRITE) Fellow grant will advance knowledge of cells as materials and translate findings for sustainable protein production. Biology is commonly described in terms of genomes and biochemical reactions. But the physical properties of cells are critical for many of the body’s functions. How cells deform to circulate through the body; how cells resist physical forces—like stretching or squeezing, and mechanical cues—like the stiffness of the cellular environment, are important for human health, and critical in many diseases. This project strives to understand the cellular ‘mechanome’, or the set of genes, proteins, and pathways that regulate how cells sense and respond to physical and mechanical cues. Findings would enable us to address fundamental questions including: How do cells integrate mechanical and soluble cues to regulate their behaviors? The vision of the research is to establish new foundational knowledge of cells as materials, and to translate this knowledge to develop innovative engineering methods to “grow” animal protein for foods. The research also includes initiatives to promote diversity in engineering and science research using food as a tool to strengthen mentorship and community.The specific goals of the research are to (1) build a systems-level knowledge of how cells sense and respond to mechanical stimuli and regulate their mechanical properties; and (2) test the hypothesis that the mechanical crosstalk between cells and scaffolds is critical for the sensory and nutrient properties of cultured meat. To build a unified knowledge of the mechanome, we will (i) investigate predicted mechanical regulators that emerged from our high throughput deformability screen; (ii) engineer a genome-wide screen to identify novel regulators of mechanical memory; and (iii) compile a mechanome web resource. To translate findings for food production, we aim to achieve efficient muscle tissue growth by (i) defining the optimal stiffness of edible microcarrier scaffolds for the myogenesis of livestock animal cells; and (ii) identifying combinations of scaffold stiffness and media additives to enhance satellite muscle cell proliferation and myotube contractility in a bioreactor context. Findings will enable the PI to address fundamental questions in mechanobiology with translational applications for protein production and tissue engineering. Complementary methods for protein production are urgently needed to address the increasing need to feed the world’s growing population to protect against disruptions in the food chain resulting from natural disasters or epidemics that limit or halt production.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.

这一促进了工程学变革和公平进步的研究思想（BRITE）GRANT将推进细胞的知识，并将其转化为可持续蛋白质生产的发现。生物学通常用基因组和生化反应来描述。但是细胞的物理特性对于人体的许多功能至关重要。细胞如何变形以通过体内循环；细胞如何抵抗物理力（例如拉伸或挤压以及机械提示），例如细胞环境的刚度，对人类健康至关重要，并且在许多疾病中至关重要。该项目致力于了解细胞“机制”，或一组基因，蛋白质和途径，这些基因，蛋白质和途径调节细胞如何感知并响应物理和机械线索。调查结果将使我们能够解决基本问题，包括：细胞如何整合机械和固体线索以调节其行为？研究的愿景是建立新的细胞基础知识作为材料，并将这些知识转化为开发创新的工程方法，以“种植”食物的动物蛋白。该研究还包括使用食物作为加强心态和社区的工具来促进工程和科学研究多样性的举措。该研究的具体目标是（1）建立系统级别的知识，了解细胞如何对机械刺激有所了解并调节其机械性能； （2）检验以下假设：细胞和支架之间的机械串扰对于培养肉的感觉和营养特性至关重要。为了建立对机制的统一知识，我们将（i）研究从高吞吐量变形屏幕中出现的预测的机械调节剂； （ii）设计一个全基因组屏幕，以识别机械记忆的新调节剂； （iii）编译机械组Web资源。为了翻译粮食生产的发现，我们旨在通过（i）定义可食用的微载体支架的最佳刚度来实现有效的肌肉组织生长，以实现牲畜动物细胞的肌发生； （ii）识别脚手架僵硬和媒体成瘾性的组合，以增强生物反应器中的卫星肌肉细胞增殖和肌管收缩力。调查结果将使PI能够通过转化蛋白质生产和组织工程来解决机械生物学中的基本问题。迫切需要使用蛋白质生产的互补方法来解决越来越多的需求，以防止限制或停止生产的自然灾害或情节造成的食物链中的中断。这一奖项反映了NSF的法定任务，并以评估基金会的知识分子功能和广泛的影响来评估CRETERIA，并被认为是珍贵的支持。

项目成果

Reduction of Intracellular Tension and Cell Adhesion Promotes Open Chromatin Structure and Enhances Cell Reprogramming.

• DOI: 10.1002/advs.202300152
• 发表时间: 2023-08
• 期刊: ADVANCED SCIENCE
• 影响因子: 15.1
• 作者: Soto, Jennifer;Song, Yang;Wu, Yifan;Chen, Binru;Park, Hyungju;Akhtar, Navied;Wang, Peng-Yuan;Hoffman, Tyler;Ly, Chau;Sia, Junren;Wong, SzeYue;Kelkhoff, Douglas O.;Chu, Julia;Poo, Mu-Ming;Downing, Timothy L.;Rowat, Amy C.;Li, Song
• 通讯作者: Li, Song