单分子分析方法研究运动蛋白
Molecular motor proteins are fascinating enzymes that power much of the movement performed by living organisms. In the first part of this lecture, I will provide an overview of the motors that move along cytoskeletal tracks (kinesin and dynein which move along microtubules and myosin which moves along actin). The main focus of this lecture is on how motor proteins work. How does a nanoscale protein convert energy from ATP hydrolysis into unidirectional motion and force production? What tools do we have at our disposal to study them? The first part of the lecture will focus on these questions for kinesin (a microtubule-based motor) and myosin (an actin-based motor), since they have been the subject of extensive studies and good models for their mechanisms have emerged. I conclude by discussing the importance of understanding motor proteins for human disease, in particular illustrating a recent biotechnology effort from Cytokinetics, Inc. to develop drugs that activate cardiac myosins to improve cardiac contractility in patients suffering from heart failure. The first part of the lecture is directed to a general audience or a beginning graduate class.
In the second part of this lecture, I will discuss our laboratories current work on the mechanism of movement by dynein, a motor protein about which we still know very little. This is a research story in progress, where some advances have been made. However, much remains to be done in order to understand how this motor works.
The third (last) part of the lecture is on mitosis, the process by which chromosomes are aligned and then segregated during cell division. I will describe our efforts to find new proteins that are important for mitosis through a high throughput RNAi screen. I will discuss how we technically executed the screen and then focus on new proteins that are we discovered that are involved in generating the microtubules that compose the mitotic spindle. I also discuss the medical importance of studying mitosis, including the development of drugs targeted to mitotic motor proteins, which are currently undergoing testing in clinical trials.
GTP结合蛋白作为调节分子
When a growth factor binds to the plasma membrane of a quiescent cell, an intracellular signaling pathway is activated telling the cell to begin growing. A key molecule in this signaling pathway is the GTP-binding protein, or G-protein, Ras. Ras can act as an on-off switch telling the cell to grow or not. In its inactive form, Ras is bound to GDP while in its active form it is bound to GTP. This exchange of nucleotides is catalysed by guanine nucleotide-exchange-factors (GEFs). The return to the inactive state occurs through the GTPase reaction, which is accelerated by GTPase-activating proteins (GAPs). In Part 1 of his talk, Dr. Wittinghofer explains how solving the three-dimensional structure of Ras, and other G-proteins, allowed him to understand the conserved mechanism by which G-proteins can act as switches. The structure also identified domains unique to each G-protein that provide the specificity for downstream signals.
以分子角度看生命的伦理挑战
讲座主讲人通过向大家介绍天主教对于干细胞研究中产生的道德问题的看法,表达了他的观点。他认为如果我们不对人类生物的本质进行研究,就无法提升思想层面的 生活品质。他呼吁大家重新进行生命科学研究,认识到科学给人类带来的好处和价值,不是盲目反科学。同时人类应重新建立神学与现代科学之间的联系,带着对人类本质的思考,展开生物学研究。
赵奇志:高精确度、高灵敏性的循环肿瘤DNA测序,助力癌症精准分子医疗
本讲座包括了DNA突变到肿瘤,基于精准分子医疗-基于肿瘤基因突变信息,液态活检,循环肿瘤DNA(ctDNA),可在各种癌症中检测到,循环肿瘤DNA(ctDNA)以及时间敏感的检测需求。CtDNA液态活检的优势;难点。提到AccuraGen核心技术。Nebula-无偏差扩增。常规NGS测序会产生较高的背景噪声,Firefly去除测序错误噪声。CfDNA ddPCR和NGS突变检测的相符性,CtDNA技术在肿瘤诊疗上的应用,不同的panel以适用不同的需要。
李进:晚期大肠癌精准医学治疗模式-从整体治疗计划到分子亚型指导
从伊马替尼开始,贝伐株治疗大肠癌开启了大肠癌靶向治疗时代的大门,介绍了分子靶向治疗。提到了分子亚型对靶向药物的指导意义。提到RAS分析。提到了精准医学面临的最大挑战以及未来的靶向治疗。
单分子超高灵敏度检测技术介绍
默克独创Erenna®单分子免疫检测平台,采用专利单分子检测技术,突破蛋白检测极限,创领生物标志新发现,助力疾病研究再创新。 SMC™技术相较于传统免疫检测技术,信噪比有了很显著的改善,使得在一个系统里可以同时检测低表达和高表达的蛋白靶标,揭示疾病相关生物标志物的微小变化。SMC™技术在经典的三明治免疫夹心原理基础上,通过创见性的洗脱步骤使得荧光素标记的检测抗体从免疫复合物中解离下来。并最终在默克Erenna®系统的毛细管检测空间内以单个分子的形式被激光激发,相应的光学信号被灵敏地记录下来并进行定量计算。检测下限可以下探到1fM。
黄志伟:CRISPR-Cpf1识别CRISPR RNA (crRNA)以及Cpf1剪切pre-crRNA成熟的分子机制
从结构生物学的角度讲解了CRISPR-Cpf1识别CRISPR RNA (crRNA)以及Cpf1剪切pre-crRNA成熟的分子机制。发现Cpf1并不是之前人们推测的二聚体状态,而是一个呈三角形的单体,位于该结构中间是一个带有正电荷的凹槽
单分子测序开启转录组学研究新时代
以基因测序技术发展为背景,阐述以第三代测序技术为核心的全长转录组测序与二代测序技术的转录组测序的差异,以及在研究基因结构等问题上所带来的巨大优势。并以经典案例为参考,阐述全长转录组测序在样品制备、实验设计及数据分析等环节的切入点和注意事项。