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.

这个促进工程学变革和公平进步的研究思路（BRITE）研究员赠款将推进细胞作为材料的知识，并将研究结果转化为可持续的蛋白质生产。生物学通常用基因组和生化反应来描述。但细胞的物理特性对身体的许多功能至关重要。细胞如何变形以在体内循环;细胞如何抵抗物理力（如拉伸或挤压）和机械线索（如细胞环境的刚度），这些对人类健康至关重要，对许多疾病至关重要。该项目致力于了解细胞的“机械组”，或调节细胞如何感知和响应物理和机械线索的基因，蛋白质和途径的集合。这些发现将使我们能够解决一些基本问题，包括：细胞如何整合机械和可溶性线索来调节它们的行为？该研究的愿景是建立细胞作为材料的新基础知识，并将这些知识转化为开发创新的工程方法，以“种植”动物蛋白质作为食物。该研究还包括利用食品作为加强导师和社区的工具来促进工程和科学研究的多样性的举措。研究的具体目标是（1）建立细胞如何感知和响应机械刺激并调节其机械特性的系统级知识;以及（2）检验细胞和支架之间的机械串扰对培养肉的感官和营养特性至关重要的假设。为了建立机械组的统一知识，我们将（i）研究从我们的高通量变形性筛选中出现的预测机械调节器;（ii）设计全基因组筛选以识别机械记忆的新型调节器;以及（iii）编译机械组网络资源。为了将研究结果转化为食品生产，我们的目标是通过以下方式实现有效的肌肉组织生长：（i）定义用于家畜动物细胞肌生成的可食用微载体支架的最佳刚度;以及（ii）确定支架刚度和培养基添加剂的组合，以增强生物反应器背景下的卫星肌细胞增殖和肌管收缩性。研究结果将使PI能够解决机械生物学中的基本问题，并将其应用于蛋白质生产和组织工程。为了满足日益增长的世界人口对蛋白质生产的日益增长的需求，以防止自然灾害或流行病导致的食物链中断，限制或停止生产，迫切需要补充蛋白质生产的方法。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值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

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