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CRISPR screen in regulatory T cells reveals modulators of Foxp3 期刊论文
NATURE, 2020
作者:  Xu, Daqian;  Wang, Zheng;  Xia, Yan;  Shao, Fei;  Xia, Weiya;  Wei, Yongkun;  Li, Xinjian;  Qian, Xu;  Lee, Jong-Ho;  Du, Linyong;  Zheng, Yanhua;  Lv, Guishuai;  Leu, Jia-shiun;  Wang, Hongyang;  Xing, Dongming;  Liang, Tingbo;  Hung, Mien-Chie;  Lu, Zhimin
收藏  |  浏览/下载:52/0  |  提交时间:2020/07/03

Regulatory T (T-reg) cells are required to control immune responses and maintain homeostasis, but are a significant barrier to antitumour immunity(1). Conversely, T-reg instability, characterized by loss of the master transcription factor Foxp3 and acquisition of proinflammatory properties(2), can promote autoimmunity and/or facilitate more effective tumour immunity(3,4). A comprehensive understanding of the pathways that regulate Foxp3 could lead to more effective T-reg therapies for autoimmune disease and cancer. The availability of new functional genetic tools has enabled the possibility of systematic dissection of the gene regulatory programs that modulate Foxp3 expression. Here we developed a CRISPR-based pooled screening platform for phenotypes in primary mouse T-reg cells and applied this technology to perform a targeted loss-of-function screen of around 500 nuclear factors to identify gene regulatory programs that promote or disrupt Foxp3 expression. We identified several modulators of Foxp3 expression, including ubiquitin-specific peptidase 22 (Usp22) and ring finger protein 20 (Rnf20). Usp22, a member of the deubiquitination module of the SAGA chromatin-modifying complex, was revealed to be a positive regulator that stabilized Foxp3 expression  whereas the screen suggested that Rnf20, an E3 ubiquitin ligase, can serve as a negative regulator of Foxp3. T-reg-specific ablation of Usp22 in mice reduced Foxp3 protein levels and caused defects in their suppressive function that led to spontaneous autoimmunity but protected against tumour growth in multiple cancer models. Foxp3 destabilization in Usp22-deficient T-reg cells could be rescued by ablation of Rnf20, revealing a reciprocal ubiquitin switch in T-reg cells. These results reveal previously unknown modulators of Foxp3 and demonstrate a screening method that can be broadly applied to discover new targets for T-reg immunotherapies for cancer and autoimmune disease.


A CRISPR-based screening platform was used to identify previously uncharacterized genes that regulate the regulatory T cell-specific master transcription factor Foxp3, indicating that this screening method may be broadly applicable for the discovery of other genes involved in autoimmunity and immune responses to cancer.


  
CRISPR tool scales up to interrogate a huge line-up of viral suspects 期刊论文
NATURE, 2020, 582 (7811) : 188-189
作者:  Gerner, Romana R.;  Raffatellu, Manuela
收藏  |  浏览/下载:19/0  |  提交时间:2020/07/03

Rapid, reliable identification of an unknown viral infection is challenging. Use of CRISPR technology can simultaneously detect nucleic acids of many viruses and pinpoint specific ones, such as the virus that causes COVID-19.


A diagnostic platform enables rapid detection of nucleic-acid sequences.


  
The promise and challenge of therapeutic genome editing 期刊论文
NATURE, 2020, 578 (7794) : 229-236
作者:  Zhong, Suijuan;  Ding, Wenyu;  Sun, Le;  Lu, Yufeng;  Dong, Hao;  Fan, Xiaoying;  Liu, Zeyuan;  Chen, Ruiguo;  Zhang, Shu;  Ma, Qiang;  Tang, Fuchou;  Wu, Qian;  Wang, Xiaoqun
收藏  |  浏览/下载:61/0  |  提交时间:2020/07/03

Genome editing, which involves the precise manipulation of cellular DNA sequences to alter cell fates and organism traits, has the potential to both improve our understanding of human genetics and cure genetic disease. Here I discuss the scientific, technical and ethical aspects of using CRISPR (clustered regularly interspaced short palindromic repeats) technology for therapeutic applications in humans, focusing on specific examples that highlight both opportunities and challenges. Genome editing is-or will soon be-in the clinic for several diseases, with more applications under development. The rapid pace of the field demands active efforts to ensure that this breakthrough technology is used responsibly to treat, cure and prevent genetic disease.


  
Picking Winners: Modelling the Costs of Technology-specific Climate Policy in the US Passenger Vehicle Sector 期刊论文
ECOLOGICAL ECONOMICS, 2017, 137
作者:  Fox, Jacob;  Axsen, Jonn;  Jaccard, Mark
收藏  |  浏览/下载:21/0  |  提交时间:2019/04/09
Climate Policy  Technology-neutral  Technology-specific  Low-carbon Vehicles  Technology Adoption Model  Simulation Model  
Rationales for technology-specific RES support and their relevance for German policy 期刊论文
ENERGY POLICY, 2017, 102
作者:  Gawel, Erik;  Lehmann, Paul;  Purkus, Alexandra;  Soederhohn, Patrik;  Witte, Katherina
收藏  |  浏览/下载:9/0  |  提交时间:2019/04/09
Renewable energy technologies  Technology-specific support  Market failures  Germany  
Demand-controlled ventilation - requirements and commissioning. Guidebook on well-functioning and energy-optimal DCV 科技报告
来源:Center for International Climate and Environmental Research-Oslo (CICERO). 出版年: 2014
作者:  Mysen, Mads;  Schild, Peter;  Cablé, Axel
收藏  |  浏览/下载:17/0  |  提交时间:2019/04/05
Energy use  Demand-controlled ventilation  Specific fan power  Energibruk  Behovsstyring  Ventilasjon  SFP  VDP::Technology: 500::Building technology: 530  
Physical properties of Norwegian mineral fillers investigated by different methods. FA 2 Competitive constructions. SP 2.1 High quality manufactured sand for concrete 科技报告
来源:Center for International Climate and Environmental Research-Oslo (CICERO). 出版年: 2012
作者:  Cepuritis, Rolands
收藏  |  浏览/下载:16/0  |  提交时间:2019/04/05
Manufactured sand  Filler  Water absorption  Porosity  Specific surface  VDP::Technology: 500