Optical Functional Genomics

光学功能基因组学

• 批准号: 10245863
• 负责人: James Thomas Neal
• 金额: $ 140.4万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-23 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10245863
• 关键词: 3-Dimensional; Biology; Biomedical Research; Cell Communication; Cells; Cellular biology; Complex; Computer Analysis; Disease; Dissociation; Genomics; Growth; Human; Human Biology; In Situ; Mammalian Cell; Methods; Modeling; Optics; Organoids; Phenotype; Research Personnel; Structure; Technology; cell type; experimental study; functional genomics; genome-wide; genomic tools; high dimensionality; insight; next generation; novel strategies; phenotypic data; preservation; programs; screening; single cell analysis; spatial relationship; three dimensional cell culture; tool; two-dimensional; whole genome

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.

项目摘要： 哺乳动物细胞生物学发生在三维空间。高通量基因组学和细胞谱研究进展 “组学方法已经使许多实验室的平行细胞生物学实验成为常规，但 这些在人细胞中的研究大多数局限于均质二维模型。这 大大减少了可以离体研究的细胞类型和相互作用的范围。尽管取得了进步 在类器官和微组织的生长中，用于3D人类生物学研究，下一代组学 但这些方法仍然需要分离这些结构并破坏它们的细胞， 生物分子进行研究。研究人员需要能够在大规模和原位研究人类生物学的工具， 从单细胞生成丰富的表型数据，同时仍保留复杂的空间关系， 3D中细胞之间的相互作用。缺乏这种工具是生物医学研究的一个主要限制。这里我 提出一种技术，将基因组规模筛选的发现潜力与信息相结合 内容的高维单细胞分析，与三维空间信息的充分整合，使丰富的， 大规模复杂细胞现象的原位表型读出。

项目成果

A genome-wide atlas of human cell morphology.

人类细胞形态的全基因组图谱。

• DOI: 10.1101/2023.08.06.552164
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Ramezani,Meraj;Bauman,Julia;Singh,Avtar;Weisbart,Erin;Yong,John;Lozada,Maria;Way,GregoryP;Kavari,SanamL;Diaz,Celeste;Haghighi,Marzieh;Batista,ThiagoM;Pérez-Schindler,Joaquín;Claussnitzer,Melina;Singh,Shantanu;Cimini,BethA