A FACS-based screen for retroviral silencing: a tool for detecting trans-sensing in mammalian cells
基于 FACS 的逆转录病毒沉默筛选:检测哺乳动物细胞反式传感的工具
基本信息
- 批准号:nhmrc : 109006
- 负责人:
- 金额:$ 13.67万
- 依托单位:
- 依托单位国家:澳大利亚
- 项目类别:NHMRC Project Grants
- 财政年份:2000
- 资助国家:澳大利亚
- 起止时间:2000-01-01 至 2002-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Retroviruses are RNA viruses that infect cells and then become integrated into the genome of the infected cell. This property has been exploited in attempts to cure genetic diseases by replacing the defective gene: the replacement can be incorporated into the retrovirus, transported into a cell, and become part of the cell?s genetic material. However, retroviruses are frequently suppressed by the host cell some time after integration, so that their genetic information becomes silent. The factors that cause silencing of retroviruses are not well understood, but it is clear that this problem is a major impediment to retrovirus-based (and perhaps all) gene therapies. In a wide variety of organisms, including plants, flies, and yeast, it has been found that multiple copies of a gene can silence each other, a phenomenon termed cosuppression. Some reports suggest that this might happen in mammals as well. We have initiated a study of retroviral silencing, using a marker protein that produces green fluorescence as a model for the replaced gene. We find that the gene is usually silenced after integration, immediately or over time, but can be reactivated by drugs that demethylate DNA or alter chromosomal structure. We now propose to extend this work by doing a systematic analysis of the frequency of retroviral silencing in human T cells, and then to develop a system to detect and analyze cosuppression by retroviruses. This work will rely on the ability of fluorescence-activated cell sorting (FACS) to detect rare events in a large population of cells, and recover those rare cells. We will also test methods of destabilizing the silent state of a retrovirus. These experiments are likely to yield information that will benefit a broad array of gene replacement efforts. A demonstration of cosuppression would be particularly interesting because of the possibility that endogenous elements in the mammalian genome are regulated by this mechanism.
逆转录病毒是感染细胞然后整合到受感染细胞的基因组中的RNA病毒。这一特性已被利用,试图通过替换有缺陷的基因来治疗遗传疾病:替换基因可以被整合到逆转录病毒中,转运到细胞中,并成为细胞的一部分?的遗传物质。然而,逆转录病毒通常在整合后一段时间被宿主细胞抑制,因此它们的遗传信息变得沉默。导致逆转录病毒沉默的因素还不清楚,但很明显,这个问题是逆转录病毒(也许是所有)基因疗法的主要障碍。在包括植物、苍蝇和酵母在内的各种生物中,已经发现一个基因的多个拷贝可以相互沉默,这种现象称为共抑制。一些研究表明,这种情况也可能发生在哺乳动物身上。我们已经开始了一项逆转录病毒沉默的研究,使用一种产生绿色荧光的标记蛋白作为替代基因的模型。我们发现,该基因通常在整合后立即或随着时间的推移而沉默,但可以通过使DNA去甲基化或改变染色体结构的药物重新激活。我们现在建议通过对人类T细胞中逆转录病毒沉默的频率进行系统分析来扩展这项工作,然后开发一种检测和分析逆转录病毒共抑制的系统。这项工作将依赖于荧光激活细胞分选(FACS)的能力,以检测大量细胞中的罕见事件,并回收这些罕见细胞。我们还将测试破坏逆转录病毒沉默状态的方法。这些实验可能会产生有益于广泛的基因替代工作的信息。共抑制的演示将是特别有趣的,因为哺乳动物基因组中的内源性元素的可能性,由这种机制进行调节。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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David Martin其他文献
The cause of death in smallpox: an examination of the pathology record.
天花死亡原因:病理记录检查。
- DOI:
- 发表时间:
2002 - 期刊:
- 影响因子:1.2
- 作者:
David Martin - 通讯作者:
David Martin
Bending Enamine Patterns of Stabilized Pentalenes into "Polymethine Ylides".
将稳定的五烯二烯的烯胺模式弯曲成“聚次甲基叶立德”。
- DOI:
10.1021/acs.orglett.3c00037 - 发表时间:
2023 - 期刊:
- 影响因子:5.2
- 作者:
Valentin Théry;Cyriac Barra;Alexandra Simeoni;J. Pécaut;Eder Tomás‐Mendivil;David Martin - 通讯作者:
David Martin
Abstract 2101: Left Superior Vena Cava Isolation In Patients Undergoing Pulmonary Vein Antrum Isolation: Impact On Atrial Fibrillation Recurrence
摘要 2101:接受肺静脉窦隔离的患者的左上腔静脉隔离:对心房颤动复发的影响
- DOI:
- 发表时间:
2006 - 期刊:
- 影响因子:0
- 作者:
C. Elayi;Tamer S. Fahmy;O. Wazni;D. Patel;Mauricio Arruda;R. Hongo;Hao Steven;S. Beheiry;Mohamed Khan;M. Kanj;Chi Keong Ching;L. Biase;Dhanunjaya R. Lakkireddy;Rong Bai;S. Bailey;K. Civello;J. Cummings;Thomas J. Dresing;David Martin;D. Burkhardt;R. Schweikert;W. Saliba;A. Natale - 通讯作者:
A. Natale
Abstract 11: Comparative Effectiveness and Safety of Oral Anticoagulants across Baseline Kidney Function
摘要 11:不同基线肾功能的口服抗凝药的有效性和安全性比较
- DOI:
- 发表时间:
2019 - 期刊:
- 影响因子:0
- 作者:
Xiaoxi Yao;Jonathan W. Inselman;N. Shah;J. Ross;R. Izem;D. Graham;David Martin;A. Thompson;M. Southworth;Konstantinos C. Siontis;Che G. Ngufor;K. Nath;N. Desai;B. Nallamothu;R. Saran;P. Noseworthy - 通讯作者:
P. Noseworthy
Designing institutions in the native title recognition space of Native Title
- DOI:
- 发表时间:
2004 - 期刊:
- 影响因子:0
- 作者:
David Martin - 通讯作者:
David Martin
David Martin的其他文献
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{{ truncateString('David Martin', 18)}}的其他基金
Planning IUCRC at University of Delaware: Center for Heirarchical Emergent Materials (CHEM)
特拉华大学 IUCCRC 规划:等级新兴材料中心 (CHEM)
- 批准号:
1939079 - 财政年份:2020
- 资助金额:
$ 13.67万 - 项目类别:
Standard Grant
CAREER: Direct Radical Functionalization of Alcohols using Cobalt Photocatalysis
职业:使用钴光催化对醇进行直接自由基官能化
- 批准号:
1952860 - 财政年份:2019
- 资助金额:
$ 13.67万 - 项目类别:
Continuing Grant
CAREER: Direct Radical Functionalization of Alcohols using Cobalt Photocatalysis
职业:使用钴光催化对醇进行直接自由基官能化
- 批准号:
1751687 - 财政年份:2018
- 资助金额:
$ 13.67万 - 项目类别:
Continuing Grant
In-Situ Studies of the Electrochemical Deposition of Functionalized Poly(thiophene) Copolymers
功能化聚噻吩共聚物电化学沉积的原位研究
- 批准号:
1808048 - 财政年份:2018
- 资助金额:
$ 13.67万 - 项目类别:
Standard Grant
In-Situ Transmission Electron Microscopy of the Electrochemical Deposition of Functionalized Poly(thiophenes)
功能化聚噻吩电化学沉积的原位透射电子显微镜
- 批准号:
1505144 - 财政年份:2015
- 资助金额:
$ 13.67万 - 项目类别:
Standard Grant
Census Programme Coordination 2011-12
2011 年 12 月人口普查计划协调
- 批准号:
ES/I030859/1 - 财政年份:2011
- 资助金额:
$ 13.67万 - 项目类别:
Research Grant
Synthesis, Structure, and Properties of Oriented Conjugated Polymer Nanofibers
定向共轭聚合物纳米纤维的合成、结构与性能
- 批准号:
1103027 - 财政年份:2011
- 资助金额:
$ 13.67万 - 项目类别:
Standard Grant
ReStore: promoting sustainable research methods resources
ReStore:促进可持续研究方法资源
- 批准号:
ES/H035125/1 - 财政年份:2010
- 资助金额:
$ 13.67万 - 项目类别:
Research Grant
Population 24/7: space-time specific population surface modelling
人口 24/7:时空特定人口表面建模
- 批准号:
ES/G031304/1 - 财政年份:2009
- 资助金额:
$ 13.67万 - 项目类别:
Research Grant
Geo-Refer 2: meeting community-specific research needs in geographical referencing
地理参考 2:满足地理参考领域特定社区的研究需求
- 批准号:
ES/F018495/1 - 财政年份:2008
- 资助金额:
$ 13.67万 - 项目类别:
Research Grant
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