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

这项促进工程中变革性和公平性进步的研究想法(BRITE)研究员基金将促进细胞作为材料的知识，并将研究成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人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量--如拉伸或挤压--以及机械信号--如细胞环境的僵硬--对人类健康非常重要，在许多疾病中也是至关重要的。这个项目致力于了解细胞的“机械组”，即调节细胞如何感知和响应物理和机械提示的一组基因、蛋白质和途径。这些发现将使我们能够解决基本的问题，包括：细胞如何整合机械和可溶的线索来调节它们的行为？这项研究的愿景是建立新的细胞作为材料的基础知识，并将这些知识转化为开发创新的工程方法，以“培养”用于食品的动物蛋白。这项研究还包括促进工程和科学研究的多样性的举措，利用食品作为加强指导和社区的工具。研究的具体目标是(1)建立关于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类的感官和营养特性至关重要的假设。为了建立对机械组的统一知识，我们将(I)调查从我们的高通量变形能力筛选中出现的预测的机械调节因子；(Ii)设计一个全基因组筛选以确定机械记忆的新调节因子；以及(Iii)编制一个机械组网络资源。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高效的肌肉组织生长：(I)确定用于牲畜动物细胞肌肉发生的可食用微载体支架的最佳硬度；以及(Ii)确定支架硬度和介质添加剂的组合，以在生物反应器的背景下提高卫星肌肉细胞的增殖和肌管的收缩能力。这些发现将使PI能够通过蛋白质生产和组织工程的翻译应用来解决机械生物学中的基本问题。迫切需要补充蛋白质生产的方法，以满足日益增长的需求，满足世界不断增长的人口的需求，以防止因限制或停止生产的自然灾害或流行病导致的食物链中断。这一奖项反映了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。

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.