Synthetic chromatin for cancer research

用于癌症研究的合成染色质

基本信息

批准号：
8768323
负责人：
Karmella Ann Haynes
金额：
$ 15.71万
依托单位：
ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8768323
关键词：
Address Affect Applications Grants Arizona Binding Biological Biological Models Cancer Intervention Cancer Remission Cell Proliferation Cells Chimeric Proteins Chromatin Clinic Clinical Clinical Research Clinical Trials Collaborations Computational Biology DNA Data Development Drug Targeting Emerging Technologies Engineering Enzyme Inhibitor Drugs Enzyme Inhibitors Epigenetic Process Faculty Frequencies Funding Gene Expression Gene Silencing Gene Targeting Genes Genetic Code Genetic Materials Genetic Transcription Goals Health system Heterogeneity Histones Human Institutes K-Series Research Career Programs Kidney Luciferases Malignant Neoplasms Marketing Mediating Medicine Mentored Research Scientist Development Award Mentors Methodology Methods Modeling Molecular Biology Molecular Conformation Nonlinear Dynamics Outcome Pathway interactions Patients Peptides Pharmaceutical Preparations Pharmacologic Substance Phenotype Piper Population Problem Solving Protein Binding Proteins Reporter Genes Repressor Proteins Research Research Personnel Research Proposals Resistance Risk Schools Scientist Silver Systems Biology Testing Time Tissues Transcription Coactivator Translational Research Tumor Suppressor Genes Tumor Suppressor Proteins United States National Institutes of Health Universities Virginia Work anticancer research base biological systems cancer cell cancer therapy career chemotherapy chromatin protein cohort design drug market fighting improved in vivo inhibitor/antagonist innovation mathematical model medical schools member new technology novel post-doctoral training professor prognostic programs protein structure public health relevance research study small molecule synthetic biology synthetic construct synthetic protein theories therapeutic gene transcription factor tumor progression tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): This is an application for a K01 award for Dr. Karmella Haynes, an assistant professor in the Ira A. Fulton School of Biological and Health Systems Engineering (SBHSE) at Arizona State University (ASU). Dr. Haynes is establishing herself as a young investigator in. This K01 award will provide Dr. Haynes with the protected time and support necessary to accomplish the following goals: (1) to become an expert in computational biology methods, (2) to become engaged in translational research collaborations with clinical scientists at the Mayo Clinic in Phoenix, AZ and Rochester, MN, and (3) to develop an independent research career. To achieve these goals, Dr. Haynes has assembled a mentoring team comprised of a principal mentor, Dr. Mark Spano, Research Professor in the SBHSE who is an expert in experimental nonlinear dynamics and complexity theory as applied to biological systems, and two co- mentors: Dr. Joshua LaBaer, a Professor and the Director of the Virginia G. Piper Center for Personalized Medicine (CPD) at the Biodesign Institute at ASU; and Dr. Pamela Silver, a Professor in the Department of Systems Biology and founding core faculty member at the Wyss Institute of Biologically Inspired Design at Harvard Medical School. The misregulation of chromatin, the central DNA-protein structures that package genetic material within human cells, is a well-recognized factor of oncogenesis and poor prognostic outcome. Dr. Haynes' research will focus on using a model system to develop and test synthetic chromatin proteins that interfere with the methyl-histone cancer-associated epigenetic signature (Aim 1), solving the problem of regulating cell-to-cell heterogeneity in the expression of chromatin-regulated genes (Aim 2), and reactivating chromatin-repressed tumor-suppressor genes with synthetic chromatin proteins (Aim 3). In Aim 1, Dr. Haynes will expand upon her research background in chromatin and synthetic biology to construct and quantitatively assess the activity of the synthetic proteins. In Aim 2, Dr. Haynes will work closely with Dr. Spano to computationally model and verify threshold protein concentrations at which cell phenotypes become uniform across a large population. In Aim 3, Dr. Haynes will work with Dr. LaBaer to complete transcription-profiling experiments in synthetic protein- treated cancer cells. The experiments will generate preliminary data that will form the basis of a methodology to use modular peptide motifs to build synthetic chromatin proteins that activate dormant therapeutic genes in a predictable, reliable manner. A study that applies this methodology to halt cancer progression in vivo without undesired pleiotropic effects will be proposed in an R01 grant application before the end of the K award.

描述（由申请人提供）：这是亚利桑那州立大学（ASU）的IRA A. Fulton生物学和卫生系统工程学院（SBHSE）IRA A. Fulton学院助理教授Karmella Haynes博士的申请。 Dr. Haynes is establishing herself as a young investigator in. This K01 award will provide Dr. Haynes with the protected time and support necessary to accomplish the following goals: (1) to become an expert in computational biology methods, (2) to become engaged in translational research collaborations with clinical scientists at the Mayo Clinic in Phoenix, AZ and Rochester, MN, and (3) to develop an independent research career. To achieve these goals, Dr. Haynes has assembled a mentoring team comprised of a principal mentor, Dr. Mark Spano, Research Professor in the SBHSE who is an expert in experimental nonlinear dynamics and complexity theory as applied to biological systems, and two co- mentors: Dr. Joshua LaBaer, a Professor and the Director of the Virginia G. Piper Center for Personalized Medicine (CPD) at the Biodesign Institute at ASU;以及系统生物学系教授兼WYSS生物学启发研究所的核心教师帕梅拉·西尔弗（Pamela Silver）博士。染色质的不正调是将遗传物质包装在人类细胞中的中央DNA-蛋白结构，是肿瘤发生和预后不良结果的公认因素。海恩斯博士的研究将集中于使用模型系统开发和测试合成染色质蛋白，这些蛋白会干扰与甲基癌癌症相关的表观遗传学特征（AIM 1）（AIM 1），求解细胞对细胞对细胞 - 细胞之间的异质性在与染色质素基因表达中的表达（AIM 2），以及与素质素 - 素质蛋白 - 素化蛋白蛋白质蛋白质蛋白质相结合的问题（（目标3）。在AIM 1中，海恩斯博士将扩展其在染色质和合成生物学方面的研究背景，以构建和定量评估合成蛋白的活性。在AIM 2中，海恩斯博士将与Spano博士紧密合作，以进行计算模型并验证阈值蛋白浓度，在该蛋白质浓度中，在大量人群中细胞表型变得均匀。在AIM 3中，Haynes博士将与Labaer博士合作，完成合成蛋白处理的癌细胞中的转录实验。实验将生成初步数据，该数据将构成使用模块化肽基序来构建合成染色质蛋白的方法的基础，该蛋白质以可预测的可靠方式激活休眠治疗基因。一项将这种方法应用于在k奖授予结束之前，将在R01赠款应用中提出一项在体内停止癌症进展的研究。