Project description:Cellular phenotypes arise from the degrees to which different genes are expressed, yet the ability to monitor these phenotypes is limited by a lack of tools to precisely control gene expression. We describe the development of allelic series of systematically compromised sgRNAs to titrate expression of human genes with CRISPR interference. Using large-scale measurements of compromised sgRNA activities, we both identify empirically validated intermediate-activity sgRNAs and derive the factors governing sgRNA activity using deep learning, enabling construction of a compact sgRNA library to titrate expression of ~2,400 essential genes and a genome-wide in silico library. Staging cells along a continuum of essential gene expression levels using sgRNA series combined with rich single-cell RNA-seq readout reveals expression threshold-specific responses and gene-specific expression-to-phenotype relationships. Our work provides a general tool to control gene expression with applications ranging from tuning of biochemical pathways to identification of suppressors for diseases of dysregulated gene expression.
Project description:The objective of this project is to study the proteome in different tissues of huntingtin knock-in allelic series in mice. In the current part of the study, cerebellum samples from the complete remaining allelic series collected at 2, 6, and 10 months were analyzed. To this end, comprehensive quantitative, label-free proteome analysis was performed using Evotec’s quantitative Deep Proteome Profiling technology.
Project description:The objective of this project is to study the proteome in different tissues of huntingtin knock-in allelic series in mice. In the current part of the study, heart samples from the complete allelic series collected at 2, 6, and 10 months were analyzed. To this end, comprehensive quantitative, label-free proteome analysis was performed using Evotec’s quantitative Deep Proteome Profiling technology.
Project description:The objective of this project is to study the proteome in different tissues of huntingtin knock-in allelic series in mice. In the current part of the study, liver samples from the complete remaining allelic series collected at 2, 6, and 10 months were analyzed. To this end, comprehensive quantitative, label-free proteome analysis was performed using Evotec’s quantitative Deep Proteome Profiling technology.
Project description:The objective of this project is to study the proteome in different tissues of huntingtin knock-in allelic series in mice. In the current part of the study, striatum samples from the complete remaining allelic series collected at 2, 6, and 10 months were analyzed. To this end, comprehensive quantitative, label-free proteome analysis was performed using Evotec’s quantitative Deep Proteome Profiling technology.
Project description:The objective of this project is to study the proteome in different tissues of huntingtin knock-in allelic series in mice. In the current part of the study, gastrocnemius samples from the complete remaining allelic series collected at 2, 6, and 10 months were analyzed. To this end, comprehensive quantitative, label-free proteome analysis was performed using Evotec’s quantitative Deep Proteome Profiling technology.
Project description:The objective of this project is to study the proteome in different tissues of huntingtin knock-in allelic series in mice. In the current part of the study, hippocampus samples from the complete remaining allelic series collected at 2, 6, and 10 months were analyzed. To this end, comprehensive quantitative, label-free proteome analysis was performed using Evotec’s quantitative Deep Proteome Profiling technology.
Project description:The objective of this project is to study the proteome in different tissues of huntingtin knock-in allelic series in mice. In the current part of the study, cortex samples from the complete remaining allelic series collected at 2, 6, and 10 months were analyzed. To this end, comprehensive quantitative, label-free proteome analysis was performed using Evotec’s quantitative Deep Proteome Profiling technology.