权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Phenotypic Screening for Longevity Interventions Using Single-cell Epigenetic Signatures

使用单细胞表观遗传特征进行长寿干预的表型筛选

基本信息

批准号：
10043841
负责人：
ALEXEY V TERSKIKH
金额：
$ 29.25万
依托单位：
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10043841
关键词：
Age Aging Animals Antibodies Apoptosis Aspirin Biological Assay Biology of Aging Blood Cells C57BL/6 Mouse Cell Count Cell Nucleus Cells Clustered Regularly Interspaced Short Palindromic Repeats Custom Designer Drugs Disease Dose Drug Prospecting Drug Screening Drug Targeting Epigenetic Process Flowcharts Genome Glioblastoma Hepatocyte Heterochromatin Histones Human Image In Vitro Inbreeding Incidence Intervention Knowledge Libraries Longevity Machine Learning Mediating Microscopy Modeling Molecular Mus Nature Normal Cell Nuclear Pattern Pharmaceutical Preparations Phenotype Plant Roots Powder dose form Rejuvenation Sirolimus Specificity Splenocyte Stains Sum Techniques Testing Toxic effect Validation Yeasts base cost deep sequencing drug candidate drug testing epigenetic profiling epigenome healthy aging histone methylation in vivo microscopic imaging neoplastic cell novel novel therapeutics research and development response screening side effect small molecule libraries tool

项目摘要

PROJECT SUMMARY Recent advances in understanding the biology of aging have raised the prospect of drug interventions to promote healthy aging in humans. However, such interventions should have essentially no toxicity or side effects. In practice, the throughput of drug testing (currently conducted in animals) is one of the major limitations for identifying interventions to promote healthy aging. Hence, a challenge is to identify candidate drugs able to induce rejuvenation and/or healthy aging, with minimal side effects in a high throughput fashion. Here we propose to take advantage of a novel high content screening approach based on imaging of epigenetic landscape in single cells. To meet the challenge, we propose to take advantage of a novel technique we have developed that is rooted in the analysis of epigenome topography at the single cell level, automated microscopy, and machine learning. “Microscopic Imaging of Epigenetic Landscapes” (MIEL) captures patterns of nuclear staining of epigenetic marks (e.g. acetylated and methylated histones) and employs machine learning to accurately distinguish between such patterns. Pertinent to this application, we have tested whether MIEL approach is suitable for building a phenotypic cell-based assay for inducers of longevity at the cellular level. Our preliminary results validated MIEL assay for a high content screening application to identify novel candidate pro-longevity compounds. In sum, we have developed and validated a high content cell-based screening assay capable of identifying pro-longevity/healthy aging compounds based on their effect on epigenetic signature. Our specific Aims are as follows: Specific Aim 1. Screen for novel inducers of cellular rejuvenation. Specific Aim 2. Validation of novel inducers of cellular rejuvenation.

项目总结