| 项目编号: | 1404084
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| 项目名称: | Collaborative Research: Manipulating Epigenetic Mechanisms to Enhance Non-Viral Transgene Expression |
| 作者: | Kaushal Rege
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| 承担单位: | Arizona State University
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| 批准年: | 2013
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| 开始日期: | 2014-08-01
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| 结束日期: | 2018-07-31
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| 资助金额: | USD426386
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| 资助来源: | US-NSF
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| 项目类别: | Standard Grant
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| 国家: | US
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| 语种: | 英语
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| 特色学科分类: | Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
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| 英文关键词: | transgene
; protein expression
; expression
; epigenetic mechanism
; order
; gene
; defense mechanism
; transgene expression
; foreign transgene
; gene expression
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| 英文摘要: | CBET - 1404084/1403214
Rege/Elmer
DNA or gene delivery to mammalian cells has several applications in biotechnology and medicine. However, the activation of foreign genes (transgenes), and subsequent efficacy of protein expression from them, is often hindered by defense mechanisms inside the host cell. For example, cells are able to control transgene protein expression by either burying existing genes inside condensed chromosomes in the nucleus in order to turn them off, or by relaxing chromosomes in order to expose genes and activate them. A family of 'epigenetic' enzymes present within cells typically controls these processes of gene regulation; enzymes that activate genes are generally classified as activators, while those that turn genes off are called repressors. In the proposed research, the investigators will study the role of these epigenetic enzymes in regulating the expression from delivered transgenes. Furthermore, tools from the emerging field of synthetic biology will be employed to design novel DNA sequences and activator enzymes that enhance protein expression from delivered transgenes. Findings from these studies will have a transformative impact on biotechnology processes and medical treatments (e.g. gene therapy) that utilize DNA or gene delivery to mammalian cells. Outreach from this project will reach K-12 students through a PCR-based molecular biology project facilitated by the Quanta program at ASU. The proposed outreach will be designed to increase participation of students from underrepresented populations in STEM activities in Arizona and Pennsylvania.
In the same way that words are neatly organized in the pages of books in a library, cellular genes are condensed by histone proteins to form chromosomes in the nucleus. Epigenetic regulation, mediated by several enzymes, plays a key role in controlling gene expression inside cells. Since recent work has shown that epigenetic mechanisms can silence viral genes, it is likely that epigenetics may also regulate the expression of foreign genes (i.e. transgenes) that are delivered in the form of plasmid DNA to mammalian cells. The goal of this project is to manipulate intracellular epigenetic enzymes in order to enhance transgene expression by (1) using drugs to inhibit repressors and to prevent the deactivation of transgenes, (2) adding designed DNA sequences to the plasmids in order to recruit activator enzymes, and (3) using principles from synthetic biology in order to design and validate novel epigenetic activator enzymes that can selectively bind transgenes and enhance their expression. These approaches will deepen our understanding of epigenetic mechanisms that regulate protein expression from foreign transgenes (plasmid DNA) in human cells, leading to increased efficacy of gene therapy treatments in medicine, and cellular engineering approaches in biotechnology.
This award is co-funded by the Biotechnology, Biochemical, and Biomass Engineering Program of the CBET Division and by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biology. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/96155
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| Appears in Collections: | 影响、适应和脆弱性
气候减缓与适应
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| Recommended Citation: | |
Kaushal Rege. Collaborative Research: Manipulating Epigenetic Mechanisms to Enhance Non-Viral Transgene Expression. 2013-01-01.
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