HIV：免疫工程的大挑战 - David Baltimore P3
本视频由科普中国和生物医学大讲堂出品
David Baltimore (Caltech) Part 3: HIV: The Grand Challenge - Engineering Immunity
Lecture Overview:
In this set of lectures, I describe the threat facing the world from the human immunodeficiency virus (HIV) and a bold proposal on how we might meet the challenge of eliminating this disease by engineering the immune system.
In part 1, I provide a broad introduction to viruses, describing their basic properties and my own history of studying the replication of RNA viruses which led to the discovery of reverse transcriptase. I also illustrate the distinguishing features of equilibrium viruses (e.g. the common cold) that have adapted to co-exist with their host and non-equilibrium viruses (e.g. HIV) that have recently jumped from another species, are not adapted to the new host, and which can lead to disastrous outcomes (e.g. loss of immune function with potential lethality in the case of HIV).
In part 2, I describe the growing health problem that is facing the world with the spread of HIV and the limitations of current drug therapies and vaccine strategies. We need new ideas for tackling this problem. Here and in the next segment, I describe bold strategies of using gene therapy to conquer HIV, The approach that I describe in this segment involves gene therapy to produce short hairpin RNAs (siRNA) that target the destruction of a critical co-receptor of HIV, which the viruses that needs to infect cells. I discuss initial proof-of-principle experiments that suggest this approach might be feasible and the next steps needed to develop this idea into a real therapy.
In this last segment, I describe another gene therapy strategy for HIV in which we propose to develop antibody-like proteins that can be expressed by a patient's B cells and will target the HIV virus for destruction. To achieve this objective, hematopoietic (blood) stem cells must to be targeted with the gene, which will ultimately develop into B cells that express the therapeutic molecule. The ultimate goal is to produce a life-long supply of anti-HIV neutralizing antibodies. In this lecture, I describe the molecular methods underlying this strategy and a development path from proof-of-principle studies in mouse to safe trials in humans. This project receives funding from the Bill and Melinda Gates Foundation.
Speaker Bio:
After serving as President of the California Institute of Technology for nine years, in 2006 David Baltimore was appointed President Emeritus and the Robert Andrews Millikan Professor of Biology. Born in New York City, he received his B.A. in Chemistry from Swarthmore College in 1960 and a Ph.D. in 1964 from Rockefeller University, where he returned to serve as President from 1990-91 and faculty member until 1994.
For almost 30 years, Baltimore was a faculty member at Massachusetts Institute of Technology. While his early work was on poliovirus, in 1970 he identified the enzyme reverse transcriptase in tumor virus particles, thus providing strong evidence for a process of RNA to DNA conversion, the existence of which had been hypothesized some years earlier. Baltimore and Howard Temin (with Renato Dulbecco, for related research) shared the 1975 Nobel Prize in Physiology or Medicine for their discovery, which provided the key to understanding the life-cycle of HIV. In the following years, he has contributed widely to the understanding of cancer, AIDS and the molecular basis of the immune response. His present research focuses on control of inflammatory and immune responses as well as on the use of gene therapy methods to treat HIV and cancer in a program called "Engineering Immunity".
Baltimore played an important role in creating a consensus on national science policy regarding recombinant DNA research. He served as founding director of the Whitehead Institute for Biomedical Research at MIT from 1982 until 1990. He co-chaired the 1986 National Academy of Sciences committee on a National Strategy for AIDS and was appointed in 1996 to head the National Institutes of Health AIDS Vaccine Research Committee.
In addition to receiving the Nobel Prize, Baltimore's numerous honors include the 1999 National Medal of Science, election to the National Academy of Sciences in 1974, the Royal Society of London, and the French Academy of Sciences. For 2007/8, he is President of the AAAS. He has published more than 600 peer-reviewed articles.
焦点粘连作为压力传感器 - Mary Beckerle P3
本视频由科普中国和生物医学大讲堂出品
Mary Beckerle (University of Utah) Part 3: Focal Adhesions as Stress Sensors
In the third segment of my seminar, I address a new frontier in cell biology, that is how cells respond to mechanical information. Cells and tissues are exposed to physical forces in vivo and excessive mechanical stress leads to a variety of pathological consequences. I describe a system for exposing cells to controlled mechanical stress and discuss the stretch response. We have discovered that the focal adhesion protein, zyxin, is exquisitely sensitive to mechanical stimulation and is required for the ability of cells to reinforce the actin cytoskeleton when challenged by exposure to cyclic stretch. See more at http://www.ibiology.org
头足纲动物的可变化的皮肤细胞 - Roger Hanlon P3
本视频由科普中国和生物医学大讲堂出品
Roger Hanlon (MBL) Part 3: Changeable Skin
Hanlon introduces the amazing adaptive coloration of cephalopods. He uses video and still photography to showcase their ability to rapidly change color, pattern and skin texture with fine control and a diversity of appearances, to produce camouflage or to send signals. He argues that all camouflage patterns in nature can be grouped into three types. In part 2, Hanlon shows us results from his lab that make a convincing case that the rapid adaptive coloration of cephalopods is controlled by their visual system; quite impressive for a color-blind animal! Part 3 focuses on the unique skin of cephalopods including the system of pigments and reflectors that allows it to quickly change to any hue and contrast, and the papillae musculature that allows the skin to deform and create multiple 3D textures.
非包膜病毒如何侵入细胞 - Stephen Harrison P3
本视频由科普中国和生物医学大讲堂出品
Stephen Harrison (Harvard) Part 3: Non-enveloped virus entry
Harrison begins his talk by asking why most non-enveloped viruses and some enveloped viruses are symmetrical in shape. He proceeds to show us lovely images of the structures obtained by x-ray crystallography of numerous viral coat proteins. Deciphering these structures allowed scientists to understand that viral coat proteins form multimers, such as dimers and pentamers, which in turn interact with a scaffold that ensures that the coat proteins are correctly placed. This arrangement results in symmetrically shaped viruses.
In Part 1, Harrison also explains that enveloped viruses infect cells by inducing the fusion of the viral and host cell membranes. He delves deeper into the molecular mechanism of membrane fusion driven by the hemagglutinin or HA protein of the influenza virus in Part 2 of his talk.
Non-enveloped viruses, on the other hand, must enter cells by a mechanism other than membrane fusion. This is the focus of Part 3. Using rotavirus as a model, Harrison and his colleagues have used a combination of Xray crystallography and electron cryomicroscopy to decipher how the spike protein on the viral surface changes its conformation and perforates the cell membrane allowing the virus to enter the cell.
牛痘病毒如何进入细胞 - Ari Helenius P3
本视频由科普中国和生物医学大讲堂出品
Ari Helenius (ETH Zurich) Part 3: Open Sesame: Cell Entry and Vaccinia Virus
Part 3 focuses on a single virus, the Vaccinia virus, as a model for cell binding, signaling and endocytosis. Fluorescently labeled Vaccinia viruses bind to and surf along host cell filopodia. Helenius lab members noticed that when Vaccinia, unlike other viruses, reached the surface of the cell body it caused the plasma membrane to form blebs. Further experiments showed that the virus tricks the cell into thinking it is apoptotic debris. This induces blebbing and subsequent uptake of the virus by macropinocytosis. Additionally, automated high throughput siRNA screening was used to screen a large number of infected cells for host genes required for Vaccinia virus uptake. Analysis of the genes identified allowed host factors and processes critical to viral infection to be identified. Expansion of this technique may provide a new source of information on pathogen-host interactions.
声乐学习与特定的轴突导向基因的表达有关 - Erich Jarvis P3
本视频由科普中国和生物医学大讲堂出品
Erich Jarvis (Duke/HHMI) Part 3: Genes specialized in vocal learning circuits
In Part 1, Jarvis explains that vocal learning is the ability to hear a sound and repeat it. Only 5 groups of mammals (including humans) and 3 groups of birds (parrots, hummingbirds and songbirds) are capable of vocal learning. Jarvis and his lab members imaged changes in gene expression in bird's brains after singing. They found that hummingbirds, songbirds and parrots each have pathways in specific areas of the brain that are not found in non-vocal learning birds. Interestingly, analogous networks exist in the human brain but not in non-vocal learning monkeys.
In Part 2, Jarvis proposes a mechanism by which vocal learning may have evolved. He suggests that the brain areas that control vocal learning are the result of a duplication of a pre-existing neural circuit that controls motor movement. A similar duplication event may have occurred during the evolution of humans with the result that both humans and Snowball, a cockatoo, can sing and dance to a beat!
In Jarvis' third talk, he demonstrates that the brain pathways necessary for vocal learning are associated with the expression of particular axonal guidance genes. He also proposes that the evolutionary events responsible for the development of vocal learning may be a general mechanism for the development of other complex behavioral traits.
枯草芽孢杆菌的不确定性和细胞结局 - Richard Losick P3
本视频由科普中国和生物医学大讲堂出品
Richard Losick (Harvard) Part 3: Stochasticity and Cell Fate
Part III presents research showing that B. subtilis uses a bet hedging strategy for coping with uncertainty.
有丝分裂后期：染色体向纺锤体两极移动 - Richard McIntosh P3
本视频由科普中国和生物医学大讲堂出品
Richard McIntosh (U. Colorado, Boulder) Part 3: Moving Chromosome to the Spindle Poles: Anaphase A
The third lecture presents evidence, largely from McIntosh's lab, that shows how microtubule depolymerization can move chromosomes in vitro and explores the nature of some of the protein complexes that can couple chromosomes to microtubules and take advantage of this reaction. See more at http://www.ibioseminars.org
Tagrisso的伴随诊断 - 陈巍学基因(31)
欢迎来到【陈巍学基因】。我们这个节目，主要是介绍基因组学，和临床分子诊断的最新技术进展。
今天，会和大家谈一谈阿斯利康在开发Tagrisso这个新药过程中对4种伴随诊断方法的研究结果。
Tagrisso是阿斯利康公司开发的一个针对EGFR基因有耐药突变的晚期非小细胞肺癌者的药物，是酪氨酸激酶抑制剂类的靶向抗癌药物。
Tagrisso可以选择性地抑制突变型的EGFR，对发生耐药的肿瘤有强抑制作用；而对野生型的EGFR的抑制作用较弱，即对身体正常表皮细胞的生长抑制作用较弱。
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王欣：体外肠道模拟系统-第3段
什么是体外肠道模拟系统，以及该模型的可靠性评估，在检测食品和药品肠道吸收方面的作用。主要介绍了单级连续发酵模型，在鸡和人的盲肠菌群试验中的具体应用。