Multi-contrast dynamic optical imaging to advance live developmental biology

项目摘要/摘要 成像对于发育生物学的研究是必不可少的。尤其是光学成像，以其高分辨率， 对我们对生物发展的理解产生了革命性的影响。在很大程度上， 成像能力定义了在发育生物学中可以研究的东西。从2D到3D，从静态到动态， 光学成像的进步使我们能够将分子遗传学与体积形态发生联系起来 标志着在动态发展的背景下研究潜在机制的令人兴奋的时代 进程。生物发展令人着迷。从单个细胞到数十亿细胞系统，细胞具有虚拟 相同的基因拥有不同的命运，能够表现出不同的行为和功能。为了澄清这一点 复杂的过程，剖析基因和表型之间的机制联系，并确定 生物体生长和生理中的生物物理、生化和生物力学因素，多对比 成像，能够探测和连接广泛的生物信息，是势在必行的，并持有 预示着发育生物学研究的下一次革命。理解发展需要 不同的模式系统，在追求特定问题方面各有优势。其中，鼠标是 高级哺乳动物模型，具有成熟的用于突变策略和人类建模的遗传工具 疾病。对老鼠的研究可以产生与人类高度相关的见解；然而，许多重要的 发育问题目前不能用老鼠模型来研究，这主要是因为它很难或 无法想象所需的信息。这种缺乏适当的成像方法是一个关键障碍， 尤其是对发育中的细胞、组织和器官的活体研究，这对全面的 对发展的理解。这项研究计划的目标是建立一个多对比度、高分辨率 动态成像平台，以促进活的发育生物学，特别是在小鼠模型中。我们的技术 创新基于光学相干层析成像(OCT)，这是一种具有微尺度的高速成像方式 分辨率和毫米级深度。最近，我们展示了实时4D(3D+时间)结构和功能 小鼠胚胎在不同时间尺度上的OCT成像，揭示了前所未有的哺乳动物发育 动力学。在此基础上，我们将开展三个项目，以开创3D注册和集成结构， 用于哺乳动物发育活体和动态研究的功能、分子和生物力学对比。这 研究计划将在发育生物学的研究中开辟新的前沿，并将迈出重要的一步 在理解哺乳动物发育方面取得了进展。

PROJECT SUMMARY/ABSTRACT Imaging is essential for the study of developmental biology. In particular, optical imaging, with its high resolution, has been making revolutionary impacts on our understanding of biological development. To a large degree, the imaging capability defines what can be studied in developmental biology. From 2D to 3D, from static to dynamic, advancements in optical imaging have enabled us to connect molecular genetics with volumetric morphogenesis and have marked an exciting era of studying the underlying mechanisms in the context of dynamic developmental process. Biological development is fascinating. From a single cell to a multi-billion cell system, cells with virtually identical genes acquire different fates and are able to exhibit diverse behaviors and functions. To elucidate this complex process, to dissect the mechanistic link between genotypes and phenotypes, and to define the roles of biophysical, biochemical and biomechanical factors in the organismal growth and physiology, multi-contrast imaging, capable of probing and bridging a wide range of biological information, is imperative and holds the promise for the next revolution in the study of developmental biology. Understanding of development requires different model systems, each with advantages in pursuit of specific questions. Among these, the mouse is the premier mammalian model with well-established genetic tools for mutagenesis strategies and modeling of human diseases. Studies on mice can produce insights that are highly relevant to human; however, many important developmental questions cannot currently be studied using the mouse model, largely because it is difficult or impossible to image the required information. This lack of proper imaging approach acts as a critical hurdle, especially for live studies of the developing cells, tissues and organs, which are essential for a comprehensive understanding of development. The goal of this research program is to establish a multi-contrast, high-resolution dynamic imaging platform to advance live developmental biology, especially in the mouse model. Our technical innovations are based on optical coherence tomography (OCT), a high-speed imaging modality with micro-scale resolution and millimeter-level depth. Recently, we demonstrated live 4D (3D+time) structural and functional OCT imaging of mouse embryos at a variety of time scales, revealing unprecedented mammalian developmental dynamics. Building on this, we will pursue three projects to pioneer 3D-registered and integrated structural, functional, molecular and biomechanical contrasts for live and dynamic studies of mammalian development. This research program will generate a new frontier in the study of developmental biology and will make a major step forward in understanding of mammalian development.