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Development of a cavitation enhancement technology to access archived tissues for epigenetic-based biomedical research

开发空化增强技术以获取存档组织以进行基于表观遗传学的生物医学研究

基本信息

批准号：
10211263
负责人：
Ian J Davis
金额：
$ 40.15万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10211263
关键词：
Acoustics Address Architecture Biological Biological Assay Biology Biomedical Research Cell Nucleus Cells Cellular Assay Chemicals Chromatin Consumption DNA DNA Fragmentation DNA Packaging DNA-Protein Interaction Data Dehydration Development Devices Diagnostic Disease Disease Resistance Enhancement Technology Epigenetic Process Epilepsy Formaldehyde Formalin Formulation Genomic DNA Goals Heating Heterogeneity Histones Human Human Development Intellectual functioning disability Legal patent Link Malignant Neoplasms Methods Mutation Nuclear Proteins Nucleic Acids Nucleosomes Paraffin Embedding Pattern Proteins Protocols documentation Reagent Regulation Regulatory Pathway Reproducibility Research Sampling Sonication Specimen Standardization Syndrome Techniques Technology Time Tissue Banks Tissue Embedding Tissue Sample autism spectrum disorder base biological specimen archives cell type chromatin immunoprecipitation crosslink driver mutation human disease innovation nanoDroplet nervous system disorder new technology next generation sequencing parallel processing preservation prevent programs sample fixation therapy resistant tissue archive tumor virtual

项目摘要

Project Summary There is a growing appreciation for the importance of epigenetic regulatory mechanisms in both normal human development and disease. The dynamic regulation of chromatin architecture is a frequently studied and central epigenetic process. Mutations in chromatin-associated proteins have been linked to neurological disorders such as intellectual disability, autism, and epilepsy, a variety of developmental syndromes, and detected in approximately 50% of human cancers, many of which are recognized as driver mutations across multiple diverse tumors. Nevertheless, many of the assays used to study chromatin biology remain cumbersome, expensive, or lack experimental robustness, problems which have resulted in large gaps in our understanding of this critical biological mechanism. Therefore, innovative new technologies that enable efficient and reproducible interrogation of epigenetic mechanisms are badly needed. We have invented a unique cavitation enhancement reagent that dramatically decreases the time and acoustic energy required for genomic DNA fragmentation in a sonication device. This proposal aims to expand the application of our cavitation enhancement technology to address the scientifically relevant challenge of extracting high quality chromatin from archival tissues. Lengthy formaldehyde fixation (FF) followed by dehydration and paraffin embedding (PE) is the standard method of archiving tissue samples. These FFPE tissue collections contain a wealth of information on human disease. However, extraction of chromatin from these specimens has proven virtually impossible because of the challenge of preserving relevant DNA-protein interactions. Preliminary data suggest that our cavitation enhancement reagent has the potential to simplify and standardize chromatin extraction from archived tissues, thereby greatly expanding the range of applications for FFPE-derived chromatin in epigenetic-based biomedical research.

项目总结