Optically mapping tissue biomechanics during neural tube closure

神经管闭合过程中光学映射组织生物力学

• 批准号: 10540467
• 负责人: Jitao Zhang
• 金额: $ 10.56万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-03 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10540467
• 关键词: 3-Dimensional; Address; Advanced Development; Affect; Apical; Atomic Force Microscopy; Award; Biochemical; Biological; Biology; Biomechanics; Biomedical Research; Biophysics; Cells; Complement; Complex; Congenital Abnormality; Cues; Data; Defect; Detection; Development; Developmental Biology; Developmental Diagnostic; Dorsal; Elasticity; Embryo; Embryonic Development; Ensure; Environmental Risk Factor; Event; Evolution; F-Actin; Failure; Gases; Gene Combinations; Gene Expression; Genetic; Goals; Gold; Grant; Hour; Human; In Situ; Knowledge; Lead; Lighting; Link; Measurement; Measures; Mechanics; Methods; Microscopic; Microscopy; Modeling; Modulus; Monitor; Morphogenesis; Morphology; Mus; Names; Neural Fold; Neural Tube Closure; Neural Tube Defects; Neural tube; Noise; Optics; Pattern; Phenotype; Pregnancy; Process; Property; Recovery; Regulation; Research; Research Personnel; Resistance; Resolution; Role; Sample Size; Sampling; Scanning; Science; Shapes; Signal Transduction; Speed; Spinal Dysraphism; Techniques; Technology; Testing; Therapeutic; Time; Tissue Engineering; Tissues; Training; absorption; base; biomechanical engineering; cell behavior; constriction; convergent extension; driving force; elastography; embryo tissue; imaging modality; improved; in vivo; innovation; instrument; light scattering; mechanical properties; mechanical stimulus; mutant mouse model; neural plate; novel; photonics; relating to nervous system; skills; technology development; technology research and development; technology validation; tissue mapping

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.

项目概要 该项目的特点是开发先进的光子技术，以应对尚未解决的重大挑战 发育生物学。 胚胎形态发生是基因表达、生化信号传导和 生物力学。虽然评估前两种方法的方法已经很成熟，但我们对生物力学的了解 由于缺乏技术方法，人们对胚胎形态发生知之甚少。阐明 形态发生的生物力学对于理解力学之间的相互作用至关重要 驱动胚胎发生的调控、基因表达和组织模式，并有可能导致令人兴奋的结果 发育缺陷治疗策略和诊断的创新。当前的组织技术 弹性测量速度缓慢且具有侵入性，因此无法测量活体 3D 内的机械特性 胚胎组织原位。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 可以快速绘制胚胎组织弹性的原位 3D 绘图 高分辨率、非侵入性、非接触方式。 经过技术验证后，我将使用该技术来解决相关开发领域的一个悬而未决的问题 组织生物力学在神经管闭合过程中的作用。本次资助的中心假设是 神经管缺陷与组织机械性能的改变有关。具体我会调查 不同阶段细胞活动（例如顶端收缩）在组织硬度变化中的作用 神经系统和特定遗传因素导致组织硬度异常变化。 这个 K25 奖项通过其培训和研究部分，将为我提供创建强大的技能 在我未来的研究中，我将利用有利的技术能力来解决生物学问题 发育生物学的重要需求。整体努力将加速我向独立的转变 技术开发和生物医学研究跨学科接口最前沿的研究者。