Optical Functional Genomics

项目摘要： 哺乳动物细胞生物学发生在3个维度上。高通量基因组学和细胞图谱研究进展 组学方法已经使大规模平行细胞生物学实验成为许多实验室的例行公事，但 这些针对人类细胞的研究大多局限于同质的二维模型。这 极大地减少了可以在体外研究的细胞类型和相互作用的范围。而且，尽管取得了进展 在生长的有机体和微组织中研究3D人类生物学，下一代组学 方法仍然需要解离这些结构并破坏它们的细胞才能提取 用于研究的生物分子。研究人员需要能够在现场大规模询问人类生物学的工具 从单个细胞生成丰富的表型数据，同时仍保留复杂的空间关系和 3D中细胞之间的交互。缺乏这样的工具是生物医学研究的一个主要限制。在这里，我 提出了一种将基因组规模筛选的发现潜力与信息相结合的技术 内容高维的单元格剖面图，充分集成了3D空间信息，使 规模复杂细胞现象的原位表型读数。

PROJECT ABSTRACT: Mammalian cell biology happens in 3 dimensions. Advances in high-throughput genomics and cellular profiling ‘omics methods have made massively-parallel cell biology experiments routine for many labs, but the vast majority of these studies in human cells have been limited to homogeneous 2-dimensional models. This drastically reduces the range of cell types and interactions that can be studied ex vivo. And, despite advances in the growth of organoids and microtissues for the study of human biology in 3D, next generation ‘omics approaches still require the dissociation of these structures and the destruction of their cells to extract biomolecules for study. Researchers need tools that can interrogate human biology at scale and in situ to generate rich phenotyping data from single cells while still preserving complex spatial relationships and interactions between cells in 3D. The lack of such tools is a major limitation in biomedical research. Here I propose a technology that combines the discovery potential of genome scale screening with the information content of high-dimensional single-cell profiling, with full integration of 3D spatial information to enable rich in situ phenotypic readout of complex cellular phenomena at scale.