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Predictable control of gene regulation through epigenetic engineering

通过表观遗传工程对基因调控进行可预测的控制

基本信息

批准号：
10021602
负责人：
Karmella Ann Haynes
金额：
$ 19.61万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-19 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10021602
关键词：
Address Affinity Antineoplastic Agents Basic Science Binding Binding Sites Biochemical Bioinformatics Biological Biological Models C-terminal Cells Chimeric Proteins Chromatin Chromatin Fiber Chromatin Structure Chromosomes Classification Clinical Trials Complex Cytoplasm DNA DNA Sequence DNA lesion Development Drug resistance Emerging Technologies Engineering Enhancers Enzymes Epigenetic Process Gene Expression Gene Expression Profiling Gene Expression Regulation Gene Silencing Generations Genes Genetic Transcription Heritability Histone H3 Histones Hyperactive behavior In Vitro Intervention Libraries Machine Learning Malignant Neoplasms Measures Mediating Medical Medical Technology Mentored Research Scientist Development Award Methods Modality Molecular Molecular Conformation Molecular Weight Nuclear Protein Nucleic Acids Oncogenes Pathway interactions Pattern Pharmaceutical Preparations Play Polycomb Protein Array Protein Engineering Proteins Regulation Reporting Research Personnel Role Site Small Interfering RNA Small RNA Structure Synthetic Genes System Technology Testing Toxic effect Transcription Initiation Transcription Initiation Site Translations Tumor Suppressor Proteins Ursidae Family Variant Work anti-cancer base cancer cell cancer recurrence chromatin protein design epigenetic therapy epigenome inhibitor/antagonist new technology novel outcome prediction programs promoter protein structure recruit small molecule inhibitor synthetic biology synthetic protein therapeutic gene therapeutic protein transcription factor trimethyllysine

项目摘要

PROJECT SUMMARY/ ABSTRACT Recent landmark discoveries have revealed that in addition to DNA lesions, epigenetic mechanisms also play a major role in cancer. Epigenetics is mediated in part by interactions of proteins and DNA that confer heritable gene expression states. Drugging the cancer epigenome is a burgeoning medical technology that currently uses small molecule inhibitors and small RNAs to disrupt hyperactive epigenetic enzymes. The proposed work will test the hypothesis that a new modality, fusion proteins that interact with the chromatin fiber, will activate therapeutic genes at sites that bear a specific pattern of cancer-related biochemical marks. The specific aims are to (2) use bioinformatic analyses to discover chromosome features that support inducible changes in gene expression states and (2) to use protein engineering to identify determinants of nuclear protein engagement.

项目摘要/摘要