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转录因子和miRNA在复杂疾病中的共调控网络研究

Transcription factors (TFs) are key regulators controlling the transcription of target genes by binding to specific DNA sequences on the promoter of target genes. Both the TFs and miRNAs are regulators of gene expression and they may mutual regulate each other to form feedback loops (FBL), or they regulate the same target gene to form a feed-forward loop (FFL). It has been reported that hundreds of potential miRNA-mediated feedback and feed-forward loops are available at the genome level. To predict the TF-miRNA co-regulatory FFL and FBL loops, we integrated multiple data of TF targets and miRNA targets including both experimentally validated and predicted. Thus, we developed a strategy to predict the TF-miRNA co-regulatory FFL and FBL loops. We used these methods to study the TF-miRNA co-regulation in specific diseases including schizophrenia and T-cell acute lymphoblastic leukemia (T-ALL). We identified and verified some key miRNA and genes in these diseases. In the T-ALL, we obtained 120 FFLs among T-ALL related genes, miRNAs and TFs. Afterwards, a T-ALL miRNA and TF co-regulatory network was constructed and its significance was tested by statistical methods. Four miRNAs in the miR-17~92 cluster and 4 important genes (CYLD, HOXA9, BCL2L11, and RUNX1) were found as hubs in the network. Particularly, we found that miR-19 was highly expressed in T-ALL patients and cell lines. Ectopic expression of miR-19 repress CYLD expression, while miR-19 inhibitor treatment induce CYLD protein expression and decreases NF-κB expression in the downstream signaling pathway. Thus, miR-19, CYLD and NF-κB form a regulatory feed-forward loop, which provides new clues for sustained activation of NF-κB in T-ALL. Some single nucleotide polymorphisms (SNPs) in miRNA genes or target sites (miRNA-related SNPs) have been proved to be associated with human diseases by affecting the miRNA mediated regulatory function. To systematically analyze miRNA-related SNPs and their effects, we performed a genome-wide scan for SNPs in human pre-miRNAs, miRNA flanking regions, target sites and designed a pipeline to predict the effects of them on miRNA-target interaction. As a result, we identified 48 SNPs in human miRNA seed regions and thousands of SNPs in 3'- untranslated regions with the potential to either disturb or create miRNA-target interactions. Furthermore, we experimentally confirmed 7 loss-of-function SNPs and 1 gain-of-function SNP by luciferase assay. All useful data were complied into miRNASNP, a user-friendly free online database (http://www.bioguo.org/miRNASNP/). These data will be a useful resource for studying miRNA function, identifying disease-associated miRNAs, and further personalized medicine.

2014-09-26 课时:34分钟

转录因子和miRNA在复杂疾病中的共调控网络研究

Transcription factors (TFs) are key regulators controlling the transcription of target genes by binding to specific DNA sequences on the promoter of target genes. Both the TFs and miRNAs are regulators of gene expression and they may mutual regulate each other to form feedback loops (FBL), or they regulate the same target gene to form a feed-forward loop (FFL). It has been reported that hundreds of potential miRNA-mediated feedback and feed-forward loops are available at the genome level.

2014-11-17 课时:34分钟

社交网络是怎样预测流行病的传播

在摸清错综复杂的人际关系网之后,尼古拉斯·克里斯塔吉斯 (Nicholas Christakis)和同事詹姆斯·福乐开始研究怎么善用这一信息。这里,他介绍了新出笼的发现:这些社会关系可以被用来及早发现流行病,控制病毒的爆发,新思想的传播,和危险行为的蔓延。

2015-02-03 课时:7分钟

Eppendorf网络讲堂第三期:优化你的发酵溶氧控制(下)

Eppendorf网络讲堂第三期:优化你的发酵溶氧控制(下)

2016-06-29 课时:59分钟

Evolution of interaction networks 相互作用网络的演化

为什么一些殖民地饲料少:蚂蚁作为神经元?蚂蚁是如何反应的互动率? 蚂蚁对相互作用的遗传变异?跟随专注研究蚂蚁殖民地发展行为的戈登,了解蚁群的两大问题:1、节约用水,2、同种的邻居竞争。

2016-07-22 课时:33分钟

松阳洲:端粒在衰老和人类疾病的信号网络

介绍了基因组的稳定性,端粒的相关作用和稳定性和衰老的相关性。端粒是人体内的衰老时钟。介绍了TIN2对端粒功能的调控模型。介绍了TIN2蛋白链接的两大假说。介绍了基于crispr/cas9技术快速制备基因修饰小鼠的流程。

2017-07-11 课时:38分钟

网络讲堂】CRISPR完整解决方案

对细胞模型、动物模型进行基因编辑是现代生物学研究最重要的进步之一。传统的基因编辑手段(ZFN,TALEN等)虽然能够成功实现基因编辑,但是这些核酸酶设计复杂且成本高昂,很难如PCR技术一般成为实验室常规技术。CRISPR以其简易、高效的特征迅速成为该领域的新宠而变为实验室常备技术。本视频以默克在CRISPR应用解决方案基础上深入浅出地探讨构建转基因细胞、动物的流程及所需工具;分析集合型CRISPR文库在功能基因筛选上的成果、科研思路以及存在的不足;详细介绍了矩阵型CRISPR文库在筛选方案、效率及准确性等方面的潜在优势。

2018-02-06 课时:18分钟

李昊旻:生物医学研究协作网络

提到如何建设好一个转化医学研究院,提到转化医学研究的主要短板,介绍了如何开始协作研究。还介绍了转化医学临床研究的基本流程以及在解决环境和资源依赖情况下的协同工作。提到了浙江大学的研究协作网络建设需求。介绍了数据的共享和再利用网络服务。

2017-08-08 课时:35分钟

2017基因编辑网络研讨会第一期

如果说搞研究就像在森林里打兔子,那么这次的研讨会,就是帮你在最牛*的森林里,提供你更牛*的猎人思路和先进武器。在原有CRISPR系统的基础上,是怎么发现并实现高效的单碱基基因编辑的?哺乳动物的单倍体细胞系,能否给你自己的研究工作带来便利和机会?为什么多个知名实验室都会与之联合发高分文章? 欢迎届时参会讨论,期待会后,可以促成不同研究组进一步的交流与合作!

2017-09-14 课时:102分钟

2017基因编辑网络研讨会第二期

2014年生物谷率先在国内举办基因编辑领域前沿学术会议,4年来,基因编辑技术已成为下一个诺奖热门。各种新型基因编辑系统层出不穷,极大开拓在科研与临床中的用途,可以预期首先在先天性遗传性疾病、单基因疾病的治疗方面,会迅速取得突破。 为此,生物谷特再次组织盛会,探讨基因编辑前沿、中国人发现的新型基因编辑系统……

2017-09-14 课时:154分钟