https://www.ibiology.org/biomedical-workforce/preprints/ Learn more at http://asapbio.org Preprints are a way in which a manuscript containing scientific results can be rapidly communicated from one scientist, or a a group of scientists, to the entire scientific community. This video by ASAPbio (Accelerating Science and Publication in biology) explains what preprints are and their benefits, how they differ from journal publications, and how scientists can use both mechanisms to communicate their work.
Просмотров: 18594 iBiology
Eric Wieschaus describes the events leading from a single celled Drosophila embryo to an embryo with many cells with distinct functions. View the whole seminar go to www.ibioseminars.org.
Просмотров: 33174 iBiology
https://www.ibiology.org/development-and-stem-cells/enhancers/ Levine discusses the important role of precisely regulating gene expression during animal development. The Drosophila embryo provides a model system because during early embryogenesis a syncytium with about 6000 synchronously dividing nuclei is formed before membranes are laid down to separate the nuclei and areas of regulated gene expression are created. These regions of specific gene expression ultimately determine the body plan of the organism. In Part 1 of his lecture, Levine emphasizes the importance of enhancers in regulating localized gene expression. Enhancers are elements located up or downstream from the transcription start site of a gene and they bind activators and repressors of gene expression. By integrating the effect of activators and repressors, enhancers produce sharp on/off boundaries of gene expression.
Просмотров: 15621 iBiology
GET UPDATED VERSION OF THIS TALK AT: https://www.ibiology.org/talks/confocal-microscopy-short-course/ Confocal microscopy is a powerful technique for acquiring three-dimensional images of biological samples. Here I discuss the basic principles of confocal microscopy, with specific discussions of the operation of laser scanning and spinning disk confocal microscopes and of their application to biology.
Просмотров: 121983 iBiology
https://www.ibiology.org/professional-development/scientific-presentations/ What is the best way to give a talk that engages and informs your audience? Dr. McConnell gives helpful advice on preparing and presenting an effective scientific talk. She reviews the basics of PowerPoint or Key Note and gives advice on choosing fonts, colors and slide styles. She also recommends ways to structure your talk so the audience stays awake and engaged. Her final recommendation is practice, practice, practice! Whether you are a graduate student presenting journal club or a tenured professor giving an invited lecture, this talk is sure to prove useful.
Просмотров: 204419 iBiology
https://www.ibiology.org/evolution/types-of-reproduction/ Youreka Sciences describes the benefits and tradeoffs of both types of reproduction (sexual and asexual) and explains why many organisms favor sexual reproduction. Talk Overview: There are two types of reproduction: asexual and sexual reproduction. Though asexual reproduction is faster and more energy efficient, sexual reproduction better promotes genetic diversity through new combinations of alleles during meiosis and fertilization. However, as Youreka Sciences explains, both of these types of reproduction can be beneficial to different organisms. About Youreka Science: Youreka Science was created by Florie Mar, PhD, while she was a cancer researcher at UCSF. While teaching 5th graders about the structure of a cell, Mar realized the importance of incorporating scientific findings into classroom in an easy-to-understand way. From that she started creating whiteboard drawings that explained recent papers in the scientific literature to the general public. Mar has created over thirty videos about the latest scientific experiments and is now joined by Alex Olson to produce more fun and engaging videos. Learn more at http://yourekascience.org/
Просмотров: 16750 iBiology
http://www.ibiology.org/ibioseminars/biophysics-chemical-biology/susan-taylor-part-1.html In this lecture, I have given an overview of protein kinase structure and function using cyclic AMP dependent kinase (PKA) as a prototype for this enzyme superfamily. I have demonstrated what we have learned from the overall structural kinome which allows us to compare many protein kinases and also to appreciate how the highly regulated eukaryotic protein kinase has evolved. By comparing many protein kinase structures, we are beginning to elucidate general rules of architecture. In addition, I have attempted to illustrate how PKA is regulated by cAMP and how it is localized to specific macromolecular complexes through scaffold proteins.
Просмотров: 49675 iBiology
http://www.ibiology.org/ibioseminars/david-baker-part-1.html Lecture Overview: Baker begins his talk by describing two reciprocal research problems. The first is how to predict the 3 dimensional structure of a protein from a specific amino acid sequence, while the second is how to determine the amino acid sequence that will generate a new protein designed to have a specific structure. Baker’s lab is addressing the second of these challenges by developing computer programs (such as Rosetta@Home) that calculate the lowest energy, or most likely, structures for differently folded amino acid sequences. Baker explains how his lab can design a new protein structure, not found in nature, and using the computer programs they have developed, determine the amino acid structure. It is then possible to back translate to the DNA sequence and synthesize the gene that can then by used to make the protein. When the structures of these synthesized proteins are determined by crystallography and compared to the predicted structures of the designed proteins, they are found to overlap very closely demonstrating that the protein design algorithms work well. In the second of his talks, Baker tells us how his lab has moved beyond designing new protein structures to designing new protein functions. The first example he describes is the development of an inhibitor of the influenza virus. Baker’s lab designed a protein structure that fits into a highly conserved region of the hemagglutinin protein found on the surface of influenza. Preliminary lab data suggests that this designed protein protects mice from infection with the flu virus. Baker also describes experiments in which proteins were designed to fit together and build multicomponent materials such as nanocages, nanolayers and nanowires. Speaker Bio: David Baker received a BA in Biology from Harvard University and a PhD in Biochemistry from the University of California, Berkeley. Currently, Baker is the Head of the Institute for Protein Design and a Professor of Biochemistry at the University of Washington, and a Howard Hughes Medical Institute Investigator. His research utilizes both experimental and computational methods to study the design of protein structures, and the mechanisms of protein folding, protein-protein and protein-small molecule interactions. Baker’s lab developed the crowd-sourced protein folding design programs Rosetta@home and Foldit. Learn more about these programs in Baker’s iBioMagazine talk and at his lab webpage http://www.bakerlab.org/static/ . Baker has won numerous awards for his work including the Raymond and Beverly Sackler International Prize in Biophysics in 2008. Baker is a member of the National Academy of Sciences and the American Academy of Sciences.
Просмотров: 31028 iBiology
https://www.ibiology.org/neuroscience/sodium-channels/ Lecture Overview: How does a baseball player react quickly enough to hit a 90 mph fastball or a tennis player to hit a 60 mph serve? All of the fast events in our bodies, such as vision, hearing, nerve conduction and muscle contraction, involve electrical signals. In Part 1 of his talk, Dr. Catterall explains how the flow of sodium and potassium ions, through specific channels in the cell membrane, creates an electrical signal in nerve and muscle cells. He describes the structure and function of the sodium channel and its important role in physiology and pharmacology. In Part 2 of his talk, Catterall describes how voltage gated sodium channels function at an atomic level. Bacterial Na+ channels in the NaChBac family contain many of the elements of mammalian Na+ channels but in a much simpler form. Using X-ray crystallography to study NaChBac proteins, Catterall and his colleagues determined which domains of sodium channels are responsible for sensing voltage differences across the cell membrane and how these domains trigger the opening of the channel pore. It was also possible to identify the structural changes leading to the slow inactivation of channels after multiple rounds of opening and closing and to understand how NaChBac establishes its specificity for Na+ ions. In his third talk, Catterall switches his focus to voltage gated calcium channels. Na+ and Ca2+ channels share a common ancestor and consequently, much of the overall structure of the voltage sensing domain and the central pore is conserved. In spite of this homology, the calcium channel selects specifically for Ca2+ ions, even in the presence of an excess of Na+. Upon entry into the cell, Ca2+ ions regulate numerous intracellular processes. Catterall explains how his group was able to engineer a bacterial calcium channel that allowed them to identify the residues required for Ca2+ selectivity. He also describes experiments demonstrating that Ca2+ ions act locally within the cell, allowing for targeted regulation of cellular functions such as learning and memory in the brain and contraction in skeletal and cardiac muscle. Speaker Bio: Bill Catterall is Professor and Chair of the Department of Pharmacology at the University of Washington where he has been a faculty member since 1977. Catterall received his BA in Chemistry from Brown University and his PhD in Physiological Chemistry from Johns Hopkins University. He was a post-doctoral fellow with Dr. Marshall Nirenberg and a staff scientist at the NIH for a few years before moving to the University of Washington. Catterall and his colleagues discovered the voltage-gated sodium and calcium channels responsible for generating the electrical impulses necessary for most physiological functions. His lab continues to study the structure and function of these channels, their physiological regulation, and their interaction with medically important drugs. Catterall is also interested in understanding how impaired channel function may lead to human disease. Catterall has been recognized with numerous awards and honors for his contributions to the fields of electrophysiology, pharmacology, neuroscience, and cell biology. These include receiving The Bristol-Myers Squibb Award for Distinguished Research in neuroscience in 2003, The Gairdner International Award of Canada in 2010, election to the U.S. National Academy of Sciences in 1989, the Institute of Medicine and the American Academy of Arts and Sciences in 2000, and as a Foreign Member of the Royal Society of London in 2008.
Просмотров: 9710 iBiology
https://www.ibiology.org/development-and-stem-cells/bicoid/ Following fertilization, the single celled embryo undergoes a number of mitotic divisions to produce a ball of cells called a blastula or blastoderm. Although these cells are all genetically identical, they gradually begin to express different gene products that reflect the regions of the adult body they will form. In my first lecture I discuss how these initial patterns of gene expression arise. In Drosophila, a maternally supplied transcription factor called Bicoid plays a particularly important role. Bcd RNA is anchored at the anterior end of the egg but is only translated after fertilization. From that anterior source, Bcd protein is thought to diffuse through the egg, establishing a concentration gradient that activates different genes at different thresholds. See more at http://www.ibioseminars.org
Просмотров: 75224 iBiology
https://www.ibiology.org/genetics-and-gene-regulation/transposable-elements/ In Part 1, Wessler introduces transposable elements (TEs); small movable pieces of DNA that can insert throughout the genome. She describes their discovery in maize by Barbara McClintock in the 1940's and their impact on the current study of genetics. Wessler goes on to provide more details about TEs and transposase, the enzyme that facilitates insertion of TEs into the target DNA. Amazingly, as much as 50% of a mammalian genome and much more of a plant genome can be made of TEs. In Part 2 of her talk, Wessler discusses work from her lab analyzing the impact of TEs on gene and genome evolution. By looking for and finding a TE currently undergoing rapid amplification, Wessler and her colleagues have been able to assess how a type of TE called a MITE can rapidly increase its copy number without killing its host, rice.
Просмотров: 32672 iBiology
https://www.ibiology.org/archive/introduction-drug-discovery-process/ The modern drug discovery process integrates our deepest understanding of the molecular basis for disease with fundamental understanding of how potential drug molecules interact with specific disease targets and the whole organism. These two lectures are intended to give a broad and general introduction to the drug discovery process. Part I focuses on the early stages of drug discovery. We describe the basic stages of the drug discovery process, beginning with how disease targets are identified. We then take you into the laboratory to show you how a popular approach, high throughput screening, is used to identify! compounds that can engage the molecular target or pathway of interest. See more at http://www.ibioseminars.org
Просмотров: 36839 iBiology
https://www.ibiology.org/genetics-and-gene-regulation/epigenetics/ In the first of his videos, Dr. Allis introduces the concept of epigenetics; a change in a cellular phenotype that is not due to DNA mutation but due to chemical modifications of proteins that result in changes in gene activation. In the nucleus, DNA is wrapped around proteins called histones to form chromatin. How tightly the chromatin is packaged determines whether genes are active or not. This switch between the “on and off” state of chromatin is regulated by chemical modification of histones. Allis describes work from his lab and others that identified the enzymes that add, remove and recognize the histone modifications. Changes in histone modification can cause a number of diseases including cancer. A key difference between genetic mutations and epigenetic modifications is that epigenetic changes are reversible making them an attractive drug target. Dr. Allis focuses on the role of epigenetics in development and disease in his second talk. Histones can be modified on a number of amino acids, particularly lysines, by the addition of acetyl or methyl groups. Combinatorial patterns of these modifications act to enhance or repress gene expression. Allis describes work from his lab and others, which demonstrates that mutations in histone (for instance a lysine to methionine mutation) may block these modifications and, thus, impact gene expression. Sadly, these “onco-histone” mutations have been identified as the cause of many diseases including pediatric brain tumors and pancreatic neuroendocrine tumors. Speaker Biography: C. David Allis is the Joy and Jack Fishman Professor and Head of the Laboratory of Chromatin Biology and Epigenetics at The Rockefeller University. Allis’ lab studies how modifications to histones, the proteins that package DNA, influence gene expression and the implications these changes have for human disease. Allis has been honored with many awards for his pioneering research including the 2015 Breakthrough Prize in Life Sciences, the 2014 Japan Prize, the 2007 Canada Gairdner International Award and many others. Allis is a member of the National Academy of Sciences USA, the American Academy of Arts and Sciences and the French Academy of Sciences. Allis received his BS in biology from the University of Cincinnati and his PhD in biology from Indiana University and he was a post-doctoral fellow at the University of Rochester.
Просмотров: 18861 iBiology
https://www.ibiology.org/cell-biology/motor-proteins/ Molecular motor proteins are fascinating enzymes that power much of the movement performed by living organisms. In this introductory 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 talk first describes the broad spectrum of biological roles that kinesin, dynein and myosin play in cells. The talk then discusses how these nanoscale proteins convert energy from ATP hydrolysis into unidirectional motion and force production, and compares common principles of kinesin and myosin. The talk concludes by discussing the role of motor proteins in disease and how drugs that modulate motor protein activity can treat human disease. Part 2 discusses recent work from the Vale laboratory and other groups, on the mechanism of movement by dynein, a microtubule motor that is less well understood than kinesin and myosin. The lecture discusses the unusual properties of dynein stepping along microtubules, which have been uncovered using single molecule techniques. The nucleotide-driven structural changes in the dynein motor domain (elucidated by X-ray crystallography and electron microscopy) are also described. A model for dynein movement in the form of an animation is presented. However, much remains to be done in order to understand how this motor works and to test which elements of this model are correct. The third (last) part of the lecture explains how the movement of mammalian dynein is regulated by other proteins such dynactin and adapter proteins. It also describes the effect of post-translational modifications of tubulin on dynein motility. This talk features the use of single molecule imaging techniques and biochemical reconstitution to study these problems. Unanswered questions on dynein regulation are also presented. Speaker Biography: Ron Vale is a Professor of Cellular and Molecular Pharmacology at the University of California, San Francisco and an Investigator of the Howard Hughes Medical Institute. He is also the founder of the iBiology project. Vale received a B.A. degree in biology and chemistry from the University of California, Santa Barbara, and a Ph.D. degree in neuroscience from Stanford University. His graduate and postdoctoral studies at the Marine Biological Laboratory led to the discovery of kinesin, a microtubule-based motor protein. Dr. Vale’s honors include the Pfizer Award in enzyme chemistry, the Lasker Award for Basic Medical Research, and elections to the National Academy of Sciences, National Academy of Medicine, and the American Academy of Arts and Sciences. Besides studying the mechanism of motor proteins, Vale’s laboratory studies mitosis, RNA biology, and the mechanism of T cell signaling.
Просмотров: 148925 iBiology
http://www.ibiology.org/ibioseminars/anna-marie-pyle-part-1.html Lecture Overview: In Part 1, Dr. Pyle explains that many RNA molecules have elaborate structures that are essential for their functions. Even mRNA, a relatively linear molecule, can contain distinctive three- dimensional structures. RNA duplexes are the units of secondary structure, and these form in regions where base-pairing occurs. Duplex regions often include internal or terminal loops, and they can contain unusual types of base-pairing. These secondary structural elements can arrange themselves to form highly complex tertiary structures. It is the variety of these tertiary structures that allows for the great functional diversity of RNA. In her second talk, Pyle focuses on the self-splicing Group II introns. These molecules are very large ribozymes that catalyze their own splicing and transposition, employing a reaction and an active-site similar to that of the eukaryotic spliceosome. To better understand the chemistry of pre-mRNA splicincg, Pyle and her group obtained a high-resolution crystal structure of the Oceanobacillus iheyensis Group IIC intron. The crystal structure provided insights into the key roles that divalent and monovalent ions play in RNA chemistry and tertiary architecture. During the final talk in this series, Pyle switches her focus to a specialized class of mechanical proteins that bind and manipulate RNA molecules. This protein family includes RNA helicases, which translocate along RNA strands and strip away associated macromolecules. However, a related set of proteins display functions different from helicase activity, including a role as RNA-activated biosensors. Through crystallographic, biochemical and cell-based studies of innate immune receptor RIG-I, Pyle has shown that this human surveillance protein recognizes and binds to small viral double stranded RNAs. The subsequent binding of ATP induces protein conformational changes that contribute to signal transduction and activation of the interferon response in vivo. Speaker Bio: Anna Marie Pyle is the William Edward Gilbert Professor of Molecular, Cellular and Developmental Biology and Professor of Chemistry at Yale University and an Investigator of the Howard Hughes Medical Institute. Pyle received her BA from Princeton University and her PhD in Chemistry from Columbia University. She was a post-doctoral fellow with Tom Cech at the University of Colorado. Before joining Yale, Pyle was a faculty member at Columbia from 1992-2002. Pyle’s lab uses enzymatic and biophysical methods to explore the complex structures of large RNA molecules, such as self-splicing introns. Her lab also studies the molecular motor proteins that operate on RNA, such as RNA helicases and RNA-activated biosensors that contribute to the vertebrate antiviral response. More information is available on Dr. Pyle’s lab page at http://pylelab.org/
Просмотров: 21566 iBiology
https://www.ibiology.org/development-and-stem-cells/control-embryonic-axis-formation-drosophila-involving-gurken/ How do complex multicellular organisms develop from single celled eggs with a single nucleus? We study this question in the fruit fly, Drosophila. In these insects, as in many other organisms, the major body plan is predetermined during oogenesis, or egg development. In the first part of the lecture, I will give an introduction to oogenesis in Drosophila, and the techniques we use to find genes that are responsible for determining the major axes of the egg and embryo. Interestingly, our analysis revealed that this process requires cell to cell communication between the oocyte and the surrounding follicle cells. It involves a signaling molecule, Gurken, which provides a localized signal from the oocyte to the follicle cells and ultimately sets up both the anterior-posterior as well as the dorso-ventral axis of the egg.
Просмотров: 18799 iBiology
https://www.ibiology.org/genetics-and-gene-regulation/mechanisms-chromosomal-dna-replication/ Part 1a: Mechanisms of Chromosomal DNA Replication: The Replication Fork: For an organism to survive, its DNA must be accurately and completely copied during each cell division. Bell explains how replication begins at the DNA replication fork. Part 1b: Mechanisms of Chromosomal DNA Replication: Initiation of Replication: Bell describes how the multi-enzyme replisome identifies the correct site for the initiation of DNA replication and begins to copy the chromosomal DNA. Part 2: Single-Molecule Studies of Eukaryotic DNA Replication: Stephen Bell’s lab determined, at the level of single molecules, the sequence of events which initiate eukaryotic DNA replication. Talk Overview: Every time a cell divides, its genomic DNA must be completely, accurately and rapidly duplicated. This feat is completed by an amazing, multi-enzyme nanomachine, called the replisome. The replisome includes one DNA helicase, one RNA polymerase and three DNA polymerases, as well as numerous non-enzymatic proteins, all of which work together at the DNA replication fork. In Part 1a, Dr. Bell gives an excellent, step-by-step description of the function of each replisome protein at the bacterial replication fork. In Part 1b, Bell focuses on the initiation of DNA replication. At the site where replication begins, chromosomal DNA is separated into two single strands. Two replisomes are then assembled on the DNA and they move away from each other in opposite directions. Bell describes how the sites for the initiation of replication are identified, how the helicase is loaded and activated, and how the replisome is assembled. As he explains, these events are significantly more complicated in eukaryotes than bacteria. In his last talk, Dr. Bell describes an assay developed in his lab to study eukaryotic DNA replication at the single molecule level. Using this assay, Bell’s lab has determined the detailed process by which eukaryotic DNA helicase loads on DNA and begins the replication process. Speaker Biography: Dr. Bell is Professor of Biology at the Massachusetts Institute of Technology and an Investigator of the Howard Hughes Medical Institute. His lab studies the assembly of multi-protein complexes called replisomes that are responsible for replicating eukaryotic chromosomal DNA, and the regulation of this process to ensure that each chromosome is accurately and completely replicated just once per cell cycle. In recognition of his contributions to the field, Bell was awarded the National Academy of Sciences Award in Molecular Biology and the ASBMB/Schering-Plough Scientific Achievement Award. Bell has also received the MIT Everett Moore Baker Memorial Teaching Award and the School of Science Teaching Prize for Excellence in Undergraduate Education. Bell is co-author of the popular Molecular Biology of the Gene textbook. Bell received his BA in biochemistry from Northwestern University and his PhD in biochemistry from the University of California, Berkeley where he worked with Robert Tjian. He was a post-doctoral fellow with Bruce Stillman at Cold Spring Harbor Laboratory before moving to MIT. Learn more about Dr. Bell’s research at his MIT and HHMI sites: http://web.mit.edu/bell-lab/ http://www.hhmi.org/scientists/stephen-p-bell
Просмотров: 13449 iBiology
https://www.ibiology.org/genetics-and-gene-regulation/telomerase/ Lecture Overview Telomerase, a specialized ribonucleprotein reverse transcriptase, is important for long-term eukaryotic cell proliferation and genomic stability, because it replenishes the DNA at telomeres. Thus depending on cell type telomerase partially or completely (depending on cell type) counteracts the progressive shortening of telomeres that otherwise occurs. Telomerase is highly active in many human malignancies, and a potential target for anti-cancer approaches. Furthermore, recent collaborative studies have shown the relationship between accelerated telomere shortening and life stress and that low telomerase levels are associated with six prominent risk factors for cardiovascular disease.
Просмотров: 146007 iBiology
https://www.ibiology.org/profiles/gene-editing-technology/ In the last few years, the term CRISPR has exploded on the global scene, and with it UC Berkeley professor Jennifer Doudna, one of the pioneers in the field, has emerged into the spotlight. From magazine covers, to news broadcasts, to social media, CRISPR is the rare scientific breakthrough that has captivated the interest of the general public. But what is CRISPR really? What are its implications now and into the future? What profound ethical questions are raised by this ability to so precisely and easily edit the genome? In a candid and far-ranging conversation with Dan Rather, Doudna leads viewers through a nuanced and captivating view of this new technology. And along the way she shares her own improbable journey into science and her lessons for others - especially young women - who want to follow in her footsteps. About the speakers: Jennifer Doudna is Professor of the Departments of Chemistry and of Molecular and Cell Biology at University of California, Berkeley and an Investigator of the Howard Hughes Medical Institute. Early in her career, she studied the structure and mechanism of ribozymes (enzymatic RNA molecules) and RNA-protein complexes. Now her research focuses on understanding how RNA molecules control gene expression in bacteria and eukaryotic cells, through CRISPR-Cas9 and RNA-mediated mechanisms, respectively. For her outstanding scientific contributions, she was elected into the American Academy of Arts and Sciences in 2002 and the National Academy of Sciences in 2003, and was awarded the 2015 Breakthrough Prize in the Life Sciences. Learn more about Jennifer Doudna's research here: http://rna.berkeley.edu/ Dan Rather has a resume that reads like a history book. He has interviewed every American president since Eisenhower and personally covered almost every important global dateline of the last 60 years, from the Civil Rights Movement to Vietnam, to Watergate to the terrorist attacks of 9/11. Rather helped pioneer the very idea that television could be a place for news, and he has kept that spirit of innovation alive by constantly pushing the boundaries of what video storytelling could accomplish. His independent production company News and Guts specializes in high-quality non-fiction content across a range of traditional and digital distribution channels. He has a special interest in telling the stories of science. Learn more about Dan Rather’s production company here: http://www.newsandgutsmedia.com/
Просмотров: 53417 iBiology
https://www.ibiology.org/cell-biology/amazing-science-ten-craziest-things-cells/ Dr. Marshall refutes the commonly held idea that cells are just bags of watery enzymes. He runs through his “Top 10 List” of unexpected and amazing things that individual cells can do. These including growing to be huge, navigating mazes, and performing feats that seem to belong in science fiction. Speaker Biography: Dr. Wallace Marshall is a Professor of Biochemistry and Biophysics at the University of California, San Francisco. He is also a Director of the Physiology Summer Course at the Marine Biological Laboratory in Woods Hole. Marshall’s lab is interested in how single cells count and measure to determine cell size, number and organization. They have developed the single celled giant ciliate Stentor coeruleus as a molecular and genomic model organism for these studies.
Просмотров: 13855 iBiology
See more: https://www.ibiology.org/genetics-and-gene-regulation/introduction-to-micrornas/ Lecture Overview: MicroRNAs are ~22 nucleotide RNAs processed from RNA hairpin structures. MicroRNAs are much too short to code for protein and instead play important roles in regulating gene expression. In humans, they regulate most protein-coding genes, including genes important in cancer and other diseases. In Part 1 of his talk, Bartel explains how microRNAs are made, how they have evolved, how they recognize and bind to target mRNA sequences, how this binding leads to the repression of the target mRNAs, and how this repression can be important for normal development and disease. In Part 2, Bartel recounts experiments measuring the effect of microRNAs on mRNA levels, protein levels and protein synthesis in mammalian cells. The results showed that almost all of the changes in protein levels and synthesis are due to changes in the amount of mRNA. Interestingly, experiments in zebrafish embryos describe a somewhat different situation. In the early embryo, initial decreases in protein synthesis are due to shortening of the mRNA polyA tail, which is followed later by a decrease in the amount of RNA. In the last part of his seminar, Bartel asks how a cell knows which hairpin RNA molecules are pri-microRNAs, and should be processed into microRNAs, and which should be ignored. He leads us through the experiments that identified some of the key conserved features of human pri-microRNAs. Speaker Bio: David Bartel studies the many roles of RNA. His lab initially studied the ability of RNA to catalyze reactions and more recently has focused on microRNAs and other regulatory RNAs. Since 2000, his lab has made fundamental discoveries regarding the genomics, biogenesis and regulatory targets of these RNAs, as well as the molecular and biological consequences of their actions in animals, plants and fungi. Bartel received his BA in Biology from Goshen College. Soon after completion of his PhD at Harvard University in 1993, he joined the Whitehead Institute as a Fellow. Currently, Bartel is Professor of Biology at the Massachusetts Institute of Technology, a Member of the Whitehead Institute and an Investigator of the Howard Hughes Medical Institute. Bartel's many contributions to our understanding of the roles of RNA have been recognized with numerous awards, including the NAS Molecular Biology Award and election to the National Academy of Sciences.
Просмотров: 111206 iBiology
https://www.ibiology.org/profiles/stockholm/ It's rare that scientists are featured in front page headlines or on the evening news, but every October that calculus shifts with certainty, because (drumroll please) it's Nobel Time! The 2016 Awards for science will be announced next week, and with an early morning call from the Nobel Committee, researchers who heretofore have labored in popular obscurity will see their lives changed forever. Over the years, iBiology has recorded science talks from numerous Nobel Laureates, and we took that opportunity to ask these luminaries what it was like...When Stockholm Called #nobelprize
Просмотров: 1695 iBiology
https://www.ibiology.org/techniques/sequencing-dna-2/ In this lecture, Weissman gives an overview of the methodology that allows the sequence of DNA to be determined. He begins by explaining the classic Sanger sequencing technique using radioactively labeled nucleotides and gel electrophoresis. Next, advances such as fluorescently labeled nucleotides and capillary electrophoresis are introduced. Weissman then explains how automation and improved computing power allowed whole genomes to be sequenced, albeit slowly and at significant expense. Finally he introduces one of the "next-gen" sequencing technologies in which DNA is sequenced directly on a slide allowing millions of pieces of DNA to be sequenced in parallel. Weissman predicts that using this vastly improved technology will soon put the cost of determining an individual's genome at as little as $1000.
Просмотров: 44153 iBiology
https://www.ibiology.org/genetics-and-gene-regulation/circadian-clocks/ Lecture Overview: Circadian rhythms are an adaptation to the 24 hr day that we experience. Takahashi begins his talk with an historic overview of how the genes controlling circadian clocks were first identified in Drosophila and the cloning tour de force that was required to identify clock genes in mice. He also describes the experiments that resulted in the realization that all cells in the body have a circadian clock, not just cells in the brain. In part 1B, Takahashi explains that the suprachiasmatic nucleus (SCN) in the brain generates a circadian rhythm of fluctuating body temperature that, in turn, signals to peripheral tissues. Heat shock factor 1 is one of the signaling molecules responsible for communicating the temperature information and resetting peripheral clocks. In Part 2, Takahashi describes how crossing many mice of different genetic backgrounds allowed his lab to identify several genes that impact the output of the clock gene system through different mechanisms. Takahashi begins the last part of his presentation with the crystal structures of BMAL and Clock, the two central activators of clock gene transcription. He goes on to describe how his lab showed that BMAL/Clock controls the DNA binding activity of transcriptional regulators of not only cycling genes, but also of basic cell functions such as RNA polymerase 2 occupancy and histone modification. Speaker Bio: Joseph Takahashi received his BA in biology from Swarthmore College, his PhD in neuroscience from the University of Oregon, and he was a post-doctoral fellow with Martin Zatz at the National Institutes of Mental Health. He then spent 26 years at Northwestern University where he was a faculty member in the Department of Neurobiology and Physiology and in 1997 he became an Investigator of the Howard Hughes Medical Institute. In 2008, Takahashi joined the University of Texas, Southwestern Medical Center as the Loyd B. Sands Distinguished Chair in Neuroscience. Using forward genetic screens in mice, Takahashi identified the first mammalian circadian gene "Clock" in 1997. Since then, his lab has gone on to identify and clone numerous circadian genes in both the brain and tissues throughout the body. Takahashi has received numerous awards and honors for his ground-breaking research including election to the National Academy of Sciences.
Просмотров: 16489 iBiology
https://www.ibiology.org/microbiology/quorum-sensing/ Bacteria, primitive single-celled organisms, communicate with chemical languages that allow them to synchronize their behavior and thereby act as enormous multi-cellular organisms. This process is called quorum sensing and it enables bacteria to successfully infect and cause disease in plants, animals, and humans. Investigations of the molecular mechanisms underlying quorum sensing are leading to the development of novel strategies to interfere with quorum sensing. These strategies form the basis of new therapies to be used as antibiotics. See more at http://www.ibioseminars.org
Просмотров: 69698 iBiology
https://www.ibiology.org/cell-biology/intracellular-fluorescent-imaging/#part-3 LIppincott-Schwartz' third lecture focuses on super-resolution imaging, or Photo Activated Localization Microscopy (PALM), a process that allows the behavior of individual fluorescent molecules to be followed.
Просмотров: 23635 iBiology
https://www.ibiology.org/evolution/origin-of-life/#part-2 Szostak begins his lecture with examples of the extreme environments in which life exists on Earth. He postulates that given the large number of Earth-like planets orbiting Sun-like stars, and the ability of microbial life to exist in a wide range of environments, it is probable that an environment that could support life exists somewhere in our galaxy. However, whether or not life does exist elsewhere, depends on the answer to the question of how difficult it is for life to arise from the chemistry of the early planets. Szostak proceeds to demonstrate that by starting with simple molecules and conditions found on the early earth, it may in fact be possible to generate a primitive, self-replicating protocell. In Part 2, Szostak focuses on work from his lab studying the membrane components of a simple protocell and in Part 3 of his lecture, he describes experiments to investigate nucleic acid replication by chemical rather than enzymatic mechanisms.
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https://www.ibiology.org/development-and-stem-cells/aging-genes/ Once it was thought that aging was just a random and haphazard process. Instead, the rate of aging turns out to be subject to regulation by transcription factors that respond to hormones and other signals. In the nematode C. elegans, in which many key discoveries about aging were first made, the aging process is subject to regulation by food intake, sensory perception, and signals from the reproductive system. Changing genes and cells that affect aging can lengthen lifespan by six fold, and can also delay age-related disease, such as the growth of tumors.
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https://www.ibiology.org/genetics-and-gene-regulation/introduction-to-micrornas/#part-2 Lecture Overview: MicroRNAs are ~22 nucleotide RNAs processed from RNA hairpin structures. MicroRNAs are much too short to code for protein and instead play important roles in regulating gene expression. In humans, they regulate most protein-coding genes, including genes important in cancer and other diseases. In Part 1 of his talk, Bartel explains how microRNAs are made, how they have evolved, how they recognize and bind to target mRNA sequences, how this binding leads to the repression of the target mRNAs, and how this repression can be important for normal development and disease. In Part 2, Bartel recounts experiments measuring the effect of microRNAs on mRNA levels, protein levels and protein synthesis in mammalian cells. The results showed that almost all of the changes in protein levels and synthesis are due to changes in the amount of mRNA. Interestingly, experiments in zebrafish embryos describe a somewhat different situation. In the early embryo, initial decreases in protein synthesis are due to shortening of the mRNA polyA tail, which is followed later by a decrease in the amount of RNA. In the last part of his seminar, Bartel asks how a cell knows which hairpin RNA molecules are pri-microRNAs, and should be processed into microRNAs, and which should be ignored. He leads us through the experiments that identified some of the key conserved features of human pri-microRNAs. Speaker Bio: David Bartel studies the many roles of RNA. His lab initially studied the ability of RNA to catalyze reactions and more recently has focused on microRNAs and other regulatory RNAs. Since 2000, his lab has made fundamental discoveries regarding the genomics, biogenesis and regulatory targets of these RNAs, as well as the molecular and biological consequences of their actions in animals, plants and fungi. Bartel received his BA in Biology from Goshen College. Soon after completion of his PhD at Harvard University in 1993, he joined the Whitehead Institute as a Fellow. Currently, Bartel is Professor of Biology at the Massachusetts Institute of Technology, a Member of the Whitehead Institute and an Investigator of the Howard Hughes Medical Institute. Bartel's many contributions to our understanding of the roles of RNA have been recognized with numerous awards, including the NAS Molecular Biology Award and election to the National Academy of Sciences.
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https://www.ibiology.org/microbiology/quorum-sensing/#part-2 Bacteria, primitive single-celled organisms, communicate with chemical languages that allow them to synchronize their behavior and thereby act as enormous multi-cellular organisms. This process is called quorum sensing and it enables bacteria to successfully infect and cause disease in plants, animals, and humans. Investigations of the molecular mechanisms underlying quorum sensing are leading to the development of novel strategies to interfere with quorum sensing. These strategies form the basis of new therapies to be used as antibiotics. See more at http://www.ibioseminars.org
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https://www.ibiology.org/evolution/hox-genes/ Neil Shubin is interested in understanding how human limbs evolved from fish fins. To answer this question, Shubin searched for a fossil intermediate between fish and tetrapods. Far in the Canadian arctic, he and his colleagues found Tiktaalik roseae, a 375 million year old fossil of a flat-headed fish with fin bones corresponding to limb and wrist bones. Shubin and his lab then switched gears and used developmental genetics to investigate the evolution of limb development. Specifically, they looked at Hox genes, known to be important in mammalian limb development. Comparing Gar fish and mouse, they found similar patterns of Hox gene expression in fish fins and mouse forelimbs. This combination of fossil and genetic evidence suggests that the distal regions of fish fins evolved into wrist bones in mammals. Speaker Biography: Dr. Neil Shubin is a Professor in the Department of Organismal Biology and Anatomy and the Committee on Evolutionary Biology at the University of Chicago. Shubin’s research focuses on understanding the evolutionary origins of new anatomical features such as limbs. Shubin is well known for his discovery of Tiktaalik roseae,the 375 million year old fossil link between fish and tetrapods. Shubin is the author of two popular science books including Your Inner Fish: A Journey into the 3.5-Billion Year History of the Human Body, named best book of 2008 by the National Academies of Science. Shubin is an elected member of the National Academy of Science, the American Academy of Arts and Sciences and the American Association for the Advancement of Science.
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https://www.ibiology.org/neuroscience/neurodegenerative-disease/ Overview: Part 1: As the world’s population ages, rates of neurodegenerative disease are increasing. Research into familial forms of these diseases is providing insight into cellular mechanisms. Part 2: Petsko’s lab has shown that cleavage of α-synuclein by caspase-1 causes α-synuclein to form aggregates. This may be a critical step in the development of Parkinson’s disease. Part 3: Studies in yeast and neuronal models have allowed Petsko’s lab to identify genes that suppress protein aggregation found in ALS. Talk Description: Dr. Petsko begins his lecture by presenting the challenges associated with a growing elderly population and a shrinking work force. As the population ages, we face an epidemic of debilitating neurodegenerative disease that will take a great financial and emotional toll on family, caregivers and society. The brains of patients with Alzheimer’s, Parkinson’s, and ALS/Lou Gehrig’s diseases are characterized by the presence of protein aggregates due to protein misfolding. While most neurodegenerative disease arises sporadically, about 10% has a direct genetic cause. Petsko explains that by studying the familiar forms, scientists have gained great insight into the cellular and molecular processes underlying these devastating diseases. In Part 2, Petsko focuses on Parkinson’s disease, the second most common neurodegenerative disease after Alzheimer’s. Petsko and his colleagues studied patients with a genetic predisposition to Parkinson’s disease and found a mutation in the α-synuclein gene that caused the protein to misfold and aggregate. In sporadically occurring cases of Parkinson’s, they discovered that α-synuclein was cleaved and the resulting protein fragment formed aggregates. Switching to yeast as a model system and then to human cells, Petsko’s lab identified caspase-1 as the protease responsible for cleaving α-synuclein. Interestingly, caspase-1 is activated during inflammation, providing a possible explanation for how head injury and brain infection may contribute to Parkinson’s. The development of caspase-1 inhibitors that can penetrate the brain would present hope for an effective treatment for Parkinson’s disease. Petsko and others also studied patients with familial amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease and he describes this work in Part 3. They knew that many of the genes mutated in ALS encode RNA-binding proteins and these proteins formed aggregates in neurons from ALS patients. Expression of two of these proteins, FUS and TDP43, in yeast resulted in the same phenotype. A screen for yeast genes that would suppress FUS/TDP43 toxicity identified five genes and all encoded RNA binding proteins. Excitingly, several of the human homologs of these genes also were shown to block FUS/TDP43 toxicity in human neuron and neonatal rat models. These encouraging results generate hope that targeted gene therapy may provide a future treatment for this terrible neurodegenerative disease. Speaker Biography: Gregory Petsko is Arthur J. Mahon Professor of Neuroscience in the Brain and Mind Research Institute at Weill Cornell Medical College. His lab studies protein structure and function with a particular focus on understanding and developing treatments or preventative therapies for age-related neurodegenerative diseases. Petsko received his B.A. from Princeton University. He was awarded a Rhodes Scholarship and completed his D.Phil. from Oxford University where he studied in Sir David Chilton Phillips’ lab. Petsko is an elected member of the National Academy of Sciences and the Academy of Medicine and has received numerous other honors and awards. Learn more about Dr. Petsko: http://brainandmind.weill.cornell.edu/lab/petsko-laboratory
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https://www.ibiology.org/microbiology/virus-infection-biology-kaposis-sarcoma/ In 1872, Moritz Kaposi first described a disease that included pigmented skin tumors and in some cases tumors of the viscera. While KS has been endemic in some areas of the world for many years, a highly aggressive and deadly form of the disease emerged concurrently with the HIV/AIDS epidemic. KS is a very unusual cancer including multiple cell types, including cells of a spindle morphology, in a single tumor. In this section of the talk, the atypical biology of this cancer it will be discussed. Epidemiological studies suggested that HIV was not the causative agent of KS. In the mid-1990s, a new human herpes virus, Kaposis sarcoma associated herpes virus (KSHV), was identified as the likely cause of KS. Development of a serological test for the presence of KSHV in patients showed that KS seroprevalence strikingly mirrored KS risk and, additionally, KS was never found in KSHV negative patients. This data strongly supported KSHV as the causative agent of KS. However, epidemiology also showed that additional cofactors are required for disease development and in the case of patients with AIDS, HIV is this cofactor. In this section of the lecture, we will look at which viral genes are expressed in KS and how they cause disease. KSHV has both a latent and lytic cycle. In the latency cycle, very few genes are expressed and no new virus is produced allowing the host cell to survive. In the lytic cycle, all open reading frames are expressed, new virus produced and the host cell killed. Greater than 95% of KSHV infected cells contain virus is in the latency cycle. A single KSHV gene, vFLIP, expressed during the latency cycle is sufficient to cause a change of cell morphology to a spindle shape. Additionally, vFLIP and a second gene kaposin B promote the expression of cytokines and the inflammatory phenotype seen in KS lesions. How this increase in the inflammatory response benefits KSHV is yet to be determined. Can the latency cycle alone account for tumorigenesis? Experiments showing that infection of latent cells is quite unstable together with the fact that latent infection with KSHV does not immortalize cells suggested that it does not. An epidemiological study in which patients were given a drug that is specific for virus in the lytic cycle (ganciclovir) resulted in a significant decrease in new KS tumors suggesting that the lytic cycle is also key to disease development. How this might happen and what this means for further understanding and treatment of KS is discussed. Don Ganem left the University of California, San Francisco in 2011 to join the Novartis Institutes for Biomedical Research in Emeryville, CA.
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https://www.ibiology.org/ecology/choanoflagellates/#part-2 Talk Overview: Animals, plants, green algae, fungi and slime molds are all forms of multicellular life, yet each evolved multicellularity independently. How did animals evolve from their single-celled ancestors? King addresses this question using a group of fascinating organisms called choanoflagellates. Choanoflagellates are the closest living relatives to animals; they are single-cell, flagellated, bacteria eating organisms found between fungi and animals on the phylogenetic tree of life. By sequencing the genomes of many choanoflagellate species, King and her colleagues have discovered that some genes required for multicellularity in animals, such as adhesion, signaling, and extracellular matrix genes, are found in choanoflagellates. This suggests that these genes may have evolved before the transition to multicellularity in animals. The choanoflagellate S. rosetta can exist as a unicellular organism or it can switch to form multicellular colonies. In fact, its life cycle can be quite complex; it can form long chain colonies, spherical colonies called rosettes, or exist in different unicellular forms. In part 2 of her talk, King explains how she chose to use S. rosetta as a simple model for animal origins. After overcoming the technical difficulty of getting S. rosetta to form rosettes in the lab, she investigated how rosettes develop and how the cells within a rosette adhere to each other. She also asked the intriguing question “What regulates rosette development?”. It turns out that rosette formation is regulated by lipids produced by environmental bacteria that S. rosetta eat. This result adds to the growing interest in how bacteria may be influencing the behavior of diverse animals including humans. Speaker Biography: While fossils sparked Nicole King’s childhood interest in evolution, she realized that the fossil record doesn’t explain fully how animals first evolved from their single celled ancestors. To answer this question, King decided to study modern day choanoflagellates. Choanoflagellates are single celled organisms that can also develop in to multicellular assemblages. King first learned about choanoflagellates while she was a graduate student with Richard Losick at Harvard University. She moved to the University of Wisconsin-Madison to do a post-doctoral fellowship focusing on choanoflagellates. In 2003, King joined the faculty at the University of California, Berkeley. Currently, she is a Professor of Molecular and Cell Biology at Berkeley and a Howard Hughes Medical Institute Investigator. King’s innovative studies have been recognized with a MacArthur Foundation Fellowship and a Pew Scholarship. King is also a Senior Fellow of the Canadian Institute for Advanced Research.
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https://www.ibiology.org/neuroscience/learning-and-memory/ In part 1 of his lecture, Dr. Poo gives an overview of the cellular basis of learning and memory. He explains how sensory input results in neuronal activity in the neural circuits that can strengthen or weaken synaptic junctions for extended periods of time. The result of this modification of the synapse is perceptual learning and memory. He describe Donald Hebb's cell assembly hypothesis that can be summed up as "cells that fire together wire together". Poo goes on to describe how the phenomenon of long-term potentiation of synapses provides support to the Hebb's hypothesis.
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http://www.ibiology.org/ibioseminars/nicole-king-part-1.html Talk Overview: Animals, plants, green algae, fungi and slime molds are all forms of multicellular life, yet each evolved multicellularity independently. How did animals evolve from their single-celled ancestors? King addresses this question using a group of fascinating organisms called choanoflagellates. Choanoflagellates are the closest living relatives to animals; they are single-cell, flagellated, bacteria eating organisms found between fungi and animals on the phylogenetic tree of life. By sequencing the genomes of many choanoflagellate species, King and her colleagues have discovered that some genes required for multicellularity in animals, such as adhesion, signaling, and extracellular matrix genes, are found in choanoflagellates. This suggests that these genes may have evolved before the transition to multicellularity in animals. The choanoflagellate S. rosetta can exist as a unicellular organism or it can switch to form multicellular colonies. In fact, its life cycle can be quite complex; it can form long chain colonies, spherical colonies called rosettes, or exist in different unicellular forms. In part 2 of her talk, King explains how she chose to use S. rosetta as a simple model for animal origins. After overcoming the technical difficulty of getting S. rosetta to form rosettes in the lab, she investigated how rosettes develop and how the cells within a rosette adhere to each other. She also asked the intriguing question “What regulates rosette development?”. It turns out that rosette formation is regulated by lipids produced by environmental bacteria that S. rosetta eat. This result adds to the growing interest in how bacteria may be influencing the behavior of diverse animals including humans. Speaker Biography: While fossils sparked Nicole King’s childhood interest in evolution, she realized that the fossil record doesn’t explain fully how animals first evolved from their single celled ancestors. To answer this question, King decided to study modern day choanoflagellates. Choanoflagellates are single celled organisms that can also develop in to multicellular assemblages. King first learned about choanoflagellates while she was a graduate student with Richard Losick at Harvard University. She moved to the University of Wisconsin-Madison to do a post-doctoral fellowship focusing on choanoflagellates. In 2003, King joined the faculty at the University of California, Berkeley. Currently, she is a Professor of Molecular and Cell Biology at Berkeley and a Howard Hughes Medical Institute Investigator. King’s innovative studies have been recognized with a MacArthur Foundation Fellowship and a Pew Scholarship. King is also a Senior Fellow of the Canadian Institute for Advanced Research.
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http://www.ibiology.org/ibioseminars/biophysics-chemical-biology/carolyn-bertozzi-part-1.html Part 1 A large part of an organism's complexity is not encoded by its genome but results from post-translational modification. Glycosylation, or the addition of sugar molecules to a protein is an example of such a modification. These sugars, or glycans, are often complex, branched molecules specific to particular cells. Cell surface glycans determine human blood types, allow viral infections and play a key role in tissue inflammation. See more at http://www.ibioseminars.org
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https://www.ibiology.org/genetics-and-gene-regulation/alternative-splicing/ In the first part of her talk, Dr. Moore explains that eukaryotic pre-mRNA contains long stretches of non-protein coding sequences interspersed with protein coding regions. By recognizing specific sequences, cellular machinery splices out the non-coding introns leaving just the protein-coding exons in mRNA. Although at first glance this may seem like a wasteful process, it is splicing that facilitates the evolution of new genes, and alternative splicing that allows a limited number of genes to produce a large number of proteins.
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https://www.ibiology.org/cell-biology/mtor-regulation David Sabatini outlines the critical role of mTOR in the regulation of growth. mTOR senses nutrient levels, growth factors and other signals and integrates a response to regulate cell growth. Growth can be defined as the increase in the size of a cell or organism, due to a gain in mass caused by nutrient uptake and assimilation. Surprisingly, how growth is regulated was not well understood until quite recently. In his first talk, David Sabatini describes how insight into this question came from an unusual direction. The small molecule drug rapamycin was known to have anti-growth effects, but its intracellular target was not known. Sabatini explains how he purified and cloned the target of rapamycin from rat brain and showed that it was a protein kinase. This protein was named mTOR in mammals and was shown to be homologous to the TOR proteins in yeast. Sabatini and others went on to show that mTOR is at the heart of two large protein complexes, mTORC1 and mTORC2, that sense upstream signals such as nutrient levels, hormones, and growth factors and direct downstream effectors to build or breakdown resources as needed for cell growth and proliferation. In his second talk, Sabatini explains that mTORC1 responds to many different upstream signals including a variety of growth factors, nutrients, and types of stress. How does mTORC1 sense all these different signals and integrate them to produce a response that regulates cell growth? Sabatini’s lab found that the first step in sensing nutrients such as amino acids is the movement of mTORC1 from a diffuse localization in the cytosol to the lysosomal surface. The lab then spent many years identifying the large number of proteins that regulate the movement of mTORC1 to the lysosome and allow it to sense nutrients and modulate the downstream processes that control cell growth. In particular, the lab identified several proteins that serve as direct sensors of metabolites or amino acids like leucine and arginine. Interestingly, mutations in several of the proteins in the nutrient sensing pathway upstream of mTORC1 are now known to cause human disease, including epilepsy. This suggests that modulation of mTOR, by inhibitors such as rapamycin, might provide a treatment for these conditions. In his final talk, Sabatini focuses on a lysosomal membrane protein that his lab had found to interact with mTORC1 and to sense arginine levels inside the lysosome. In some cell types, the amino acids needed to build new proteins are not taken up as free amino acids but instead come from the breakdown of proteins in the lysosome. This led the lab to ask which arginine-rich proteins are being degraded in the lysosome, which led to the realization that ribosomal proteins are amongst the most arginine-rich proteins in mammalian cells. After many more experiments, they showed that mTORC1 regulates a balance between the biogenesis of ribosomes, and the breakdown of ribosomes (known as ribophagy), dependent on the nutritional state of the cell. Ribophagy seems to be particularly important for supplying the cell with nucleosides during nutrient starvation. Speaker Biography: Dr. David M. Sabatini is a member of the Whitehead Institute for Biomedical Research, a professor of Biology at the Massachusetts Institute of Biology (MIT), an investigator of the Howard Hughes Medical Institute, a senior member of the Broad Institute of Harvard and MIT and a member of the Koch Institute for Integrative Cancer Research at MIT. His lab is interested in the regulation of growth and metabolism in mammals, with a focus on the critical mTOR pathway. Research from Sabatini’s lab has led to a better understanding of the role of the mTOR pathway in diseases such as cancer and diabetes, as well as in aging. Sabatini received his undergraduate degree in biology from Brown University. As a MD/PhD student at Johns Hopkins University School of Medicine, he did his first experiments on rapamycin and mTOR in the lab of Solomon H. Snyder. After completing his MD/PhD in 1997, Sabatini started his own lab as a Whitehead fellow at the Whitehead Institute. In 2002, he became a member of the Whitehead Institute and a faculty member at MIT. Sabatini’s groundbreaking work has been recognized with numerous awards and honors including the National Academy of Science Award in Molecular Biology (2014), the Dickson Prize in Medicine (2017), the Lurie Prize in Biomedical Sciences (2017), and the Switzer Prize (2018). Sabatini was elected to the National Academy of Sciences in 2016. Learn more about the research being done in Sabatini’s lab here: http://sabatinilab.wi.mit.edu and here: https://www.hhmi.org/scientists/david-m-sabatini
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https://www.ibiology.org/biochemistry/protein-kinase/#part-2 In this lecture, I have given an overview of protein kinase structure and function using cyclic AMP dependent kinase (PKA) as a prototype for this enzyme superfamily. I have demonstrated what we have learned from the overall structural kinome which allows us to compare many protein kinases and also to appreciate how the highly regulated eukaryotic protein kinase has evolved. By comparing many protein kinase structures, we are beginning to elucidate general rules of architecture. In addition, I have attempted to illustrate how PKA is regulated by cAMP and how it is localized to specific macromolecular complexes through scaffold proteins.
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https://www.ibiology.org/biophysics/super-resolution/ Zhuang begins her lecture by explaining that the resolution of traditional light microscopy is about 200 nm due to the diffraction of light. This diffraction limit has long hampered the ability of scientists to visualize individual proteins and sub-cellular structures. The recent development of sub-diffraction limit, or super resolution, microscopy techniques, such as STORM, allows scientists to obtain beautiful images of individual labeled proteins in live cells. In Part 2 of her talk, Zhuang gives two examples of how her lab has used STORM; first to study the chromosome organization of E. coli and second, to determine the molecular architecture of a synapse.
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https://www.ibiology.org/microbiology/developmental-biology-simple-organism-bacillus-subtilis/#part-3 Part III presents research showing that B. subtilis uses a bet hedging strategy for coping with uncertainty.
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https://www.ibiology.org/microbiology/quorum-sensing/#part-1 Bacteria communicate with chemical languages in a process called quorum sensing. Bonnie Bassler explains the role of this communication in the symbiotic relationship between bacteria and squid. Quorum sensing is also critical to the ability of bacteria to cause disease. Watch the whole lecture at www.ibioseminars.org.
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https://www.ibiology.org/microbiology/plasmodium-falciparum/#part-1 This brief set of three lectures gives a very general overview of malaria, the disease and Plasmodium falciparum, the causative agent of the most deadly form. Basic research as well as drug development efforts will also be covered in parts two and three of this series.
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http://www.ibiology.org/ibioseminars/robert-langer-part-1.html Talk Overview: The traditional way of taking a drug, such as a pill or injection, often results in plasma drug levels that cycle between too high and too low. To better maintain drug levels in the effective range, scientists have developed a variety of systems that release drugs at a steady rate for days or even years. In his first talk, Bob Langer gives an overview of many of these controlled release technologies, including polymer and pump systems. Langer begins Part 2 with the story of how he became interested in drug release technologies, which is also a story of the power of perseverance. As a post-doc with Judah Folkman, and after much trial and error, Langer developed a polymer system that provided a slow and constant release of an anti-angiogenesis factor. Initially, his results were met with skepticism, by both scientists and the patent office. Today, many, many companies have developed peptide delivery systems based on that original work. Langer also describes ongoing research in areas such as targeted drug delivery and externally controlled microchips designed for drug delivery. In Part 3, Langer focuses on the materials used in drug delivery and medical devices. Many of the original materials used in medicine were adapted from completely unrelated uses and often generated their own problems. Langer describes work by his lab and others to make polymers designed for specific medical uses. For instance, a porous polymer can be shaped into an ear or nose and act as a scaffold onto which a patient’s cells can be seeded to grow a new structure. Different polymers have been successfully used as scaffolds to grow new blood vessels or artificial skin for burn victims. Speaker Biography: Robert Langer is the David H. Koch Institute Professor at the Massachusetts Institute of Technology. Research in Langer’s lab focuses on the development of polymers for use in drug delivery devices that will release molecules such as drugs, proteins, RNA or DNA at controlled rates and for extended periods of time. His lab also is working on methods to create new tissues such as cartilage, skin and liver for use in medicine. Langer has written over 1250 articles and has over 1000 patents; he is the most cited engineer ever. He has been honored with numerous awards including being one of only seven people to receive both the US National Medal of Science and the National Medal of Technology and Innovation. He is also one of only a few people to be elected to the US National Academy of Sciences, Institute of Medicine and National Academy of Engineering. He is the only engineer to win the Gairdner Foundation International Award. In 2014, Langer received the Breakthrough Prize in Life Sciences and the Kyoto Prize. Langer received his BS in Chemical Engineering from Cornell University and his ScD in Chemical Engineering from MIT.
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https://www.ibiology.org/neuroscience/connectome/#part-2 Talk Overview: The human brain is extremely complex with much greater structural and functional diversity than other organs and this complexity is determined both by one's experiences and one's genes. In Part 1 of his talk, Lichtman explains how mapping the connections in the brain (the connectome) may lead to a better understanding of brain function. Together with his colleagues, Lichtman has developed tools to label individual cells in the nervous system with different colors producing beautiful and revealing maps of the neuronal connections. Using transgenic mice with differently colored, fluorescently labeled proteins in each neuron (Brainbow mice), Lichtman and his colleagues were able to follow the formation and destruction of neuromuscular junctions during mouse development. This work is the focus of Part 2. In Part 3, Lichtman asks whether some day it might be possible to map all of the neural connections in the brain. He describes the technical advances that have allowed him and his colleagues to begin this endeavor as well as the enormous challenges to deciphering the brain connectome. Speaker Bio: Jeff Lichtman's interest in how specific neuronal connections are made and maintained began while he was a MD-PhD student at Washington University in Saint Louis. Lichtman remained at Washington University for nearly 30 years. In 2004, he moved to Harvard University where he is Professor of Molecular and Cellular Biology and a member of the Center for Brain Science. A major focus of Lichtman's current research is to decode the map of all the neural connections in the brain. To this end, Lichtman and his colleagues have developed exciting new tools and techniques such as "Brainbow" mice and automated ultra thin tissue slicing machines.
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https://www.ibiology.org/cell-biology/mitochondria/ Dr. Nunnari explains that mitochondria are derived from prokaryotes and played a pivotal role in the evolution of eukaryotes. In an aerobic environment, mitochondria produce energy, in the form of ATP. This energy allowed eukaryotes to develop into complex cells and organisms. Mitochondria are also fascinating because they have retained their own genome and are dynamic organelles that communicate with other compartments in the eukaryotic cell.
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https://www.ibiology.org/cell-biology/yeast-life-cycle/ Murray begins his talk by explaining why he studies sex in yeast not humans. He describes the yeast life cycle including the decision to bud in the absence of a mate, or to shmoo and mate in the presence of yeast of the correct mating type. In either case, the cells must switch from uniform to non-uniform or polarized growth. Mating cells must also recognize a chemical signal and move towards a target cell. Murray explains the molecular details known to underlie the response to the chemical signal. In Part 2, Murray describes experiments done in his lab to learn more about mating in yeast. These experiments provide an example of how models are proposed, how experiments are designed to discriminate between the models and how further experiments may be needed to address questions raised by the models.
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