Optically mapping tissue biomechanics during neural tube closure

项目摘要 该项目的特点是先进的光子技术的发展，以攻击一个主要的未满足的挑战， 发育生物学 胚胎的形态发生是基因表达、生化信号传导和 生物力学虽然评价前两种方法已经很成熟，但我们对生物力学的了解 由于缺乏技术手段，对胚胎形态发生知之甚少。阐明 形态发生的生物力学基础对于理解机械和生物力学之间的相互作用至关重要。 调控，基因表达和组织模式，驱动胚胎发生，并将潜在地导致令人兴奋的 在治疗策略和发育缺陷诊断方面的创新。组织的当前技术 弹性测量是缓慢和侵入性的，因此不能在活体3D内测量机械性能 原位胚胎组织。该项目将开发一种全光学方法（线扫描布里渊显微镜， LSBM）来满足这一未满足的需求。LSBM允许原位快速3D映射胚胎组织的弹性， 高分辨率、非侵入性、非接触式。 在技术验证之后，我将使用该技术来解决开发领域相关的一个公开问题 组织生物力学在神经管闭合过程中的作用。这项资助的核心假设是 神经管缺陷与组织机械性能的改变有关。具体来说，我会调查 细胞活动，如顶端收缩，在不同阶段组织硬度变化中的作用 神经胚形成和特定的遗传因素导致组织硬度的异常变化。 这个K25奖，通过其培训和研究部分，将为我提供技能，创造一个强大的 在我未来的研究中，我将利用使能技术能力来解决生物学问题。 发育生物学的重要需求。整体的努力将加速我向独立的过渡 在技术开发和生物医学研究的跨学科接口的最前沿的研究员。

Project Summary This project features the development of advanced photonic technology to attack a major unmet challenge in developmental biology. Embryonic morphogenesis results from a complex combination of gene expression, biochemical signaling, and biomechanics. While methods to evaluate the first two are well established, our knowledge of biomechanics of the embryo morphogenesis is poorly understood because of the lack of technical approaches. Elucidating the biomechanics underlying morphogenesis is essential towards understanding the interplay between mechanical regulation, gene expression and tissue patterning that drive embryogenesis, and will potentially lead to exciting innovations in therapeutic strategies and diagnostics for developmental defects. Current technology for tissue elasticity measurement is slow and invasive, thus cannot measure mechanical properties within living 3D embryonic tissue in-situ. This project will develop an all-optical approach (line-scanning Brillouin microscopy, LSBM) to fulfill this unmet need. LSBM allows rapid 3D mapping of the elasticity of embryonic tissue in-situ with high-resolution, non-invasive, and non-contact manner. After technology validation, I will use this technique to address an open question of the development field related to the role of tissue biomechanics in the process of neural tube closure. The central hypothesis of this grant is that the neural tube defect is related to the altered mechanical properties of tissue. Specifically, I will investigate the role of cellular activities, such as apical constriction, in the stiffness change of tissue during different stages of neurulation and specific genetic factors contribute to the abnormal changes in tissue stiffness. This K25 award, through its training and research components, will provide me with the skills to create a strong biological part in my future research, in which I will utilize the enabling technological capabilities to address the important needs in developmental biology. The overall effort will hasten my transition to being an independent investigator at the forefront of the interdisciplinary interface of technology development and biomedical research.