iBiology: Subtitled versions

https://www.ibiology.org/development-and-stem-cells/x-chromosome-inactivation The X chromosome is many time larger than the Y chromosome. To compensate for this genetic inequality, female mammalian cells undergo X chromosome inactivation of one X chromosome. Dr. Jeannie Lee explains the how and why of X chromosome inactivation. Talk Overview: Part 3 of 3: And in her last talk, Lee describes how X inactivation is nucleated and spreads across the X chromosome. The Xist lncRNA is known to be necessary and sufficient for X inactivation. Lee describes experiments that identified the factors that tether Xist to the X chromosome and showed how Xist spreads to cover the entire X chromosome. She then goes on to explain that Xist blocks transcription in three ways: 1) Xist recruits factors that repress transcription via epigenetic modification such as histone methylation 2) Xist repels factors that open chromatin preparing it for transcription and 3) Xist changes the 3 dimensional organization of chromosomes. Lee ends with a model of our current understanding of the complex but critical process of X chromosome inactivation. Speaker Biography: Dr. Jeannie Lee is a Professor in the Department of Genetics at Harvard Medical School and in the Department of Molecular Biology at Massachusetts General Hospital (MGH). Her lab uses X chromosome inactivation as a model to study epigenetic regulation by long noncoding RNAs. Lee received her AB in biochemistry and molecular biology from Harvard University and her MD/PhD from the University of Pennsylvania School of Medicine. She was a postdoctoral fellow at the Whitehead Institute and a resident at MGH before joining Harvard/MGH as a faculty member in 1997. Lee was also an HHMI Investigator from 2001-2018. She is a member of the National Academy of Sciences and a Fellow of the American Association for the Advancement of Science. Lee has been honored with numerous awards including the 2016 Centennial Prize from the Genetics Society of America, the 2016 Lurie Prize from the Foundation for the National Institutes of Health, and the 2010 Molecular Biology Award from the National Academy of Sciences. In 2018, she was President of the Genetics Society of America. Learn more about Dr. Lee’s research here: https://www.x-inactivation-lee-lab.org

https://www.ibiology.org/development-and-stem-cells/x-chromosome-inactivation The X chromosome is many time larger than the Y chromosome. To compensate for this genetic inequality, female mammalian cells undergo X chromosome inactivation of one X chromosome. Dr. Jeannie Lee explains the how and why of X chromosome inactivation. Talk Overview: Part 2 of 3: In her second talk, Lee elaborates on the early steps of X inactivation. Very early in development, cells “count” the number of X chromosomes and decide if one needs to be inactivated, and if so which one. There is a region of the X chromosome called the X inactivation center which is enriched in long non-coding RNAs (lncRNAs). Lee explains how she and others showed that by sensing the ratio of two specific lncRNAs the cell can determine how many X chromosomes are present. Further studies showed that two different lncRNAs are responsible for randomly determining which X chromosome will be inactivated. Finally, she discusses the hypothesis that the allelic choice mechanism depends on a transient chromosomal pairing event that occurs at the beginning of the dosage compensation process. Speaker Biography: Dr. Jeannie Lee is a Professor in the Department of Genetics at Harvard Medical School and in the Department of Molecular Biology at Massachusetts General Hospital (MGH). Her lab uses X chromosome inactivation as a model to study epigenetic regulation by long noncoding RNAs. Lee received her AB in biochemistry and molecular biology from Harvard University and her MD/PhD from the University of Pennsylvania School of Medicine. She was a postdoctoral fellow at the Whitehead Institute and a resident at MGH before joining Harvard/MGH as a faculty member in 1997. Lee was also an HHMI Investigator from 2001-2018. She is a member of the National Academy of Sciences and a Fellow of the American Association for the Advancement of Science. Lee has been honored with numerous awards including the 2016 Centennial Prize from the Genetics Society of America, the 2016 Lurie Prize from the Foundation for the National Institutes of Health, and the 2010 Molecular Biology Award from the National Academy of Sciences. In 2018, she was President of the Genetics Society of America. Learn more about Dr. Lee’s research here: https://www.x-inactivation-lee-lab.org

https://www.ibiology.org/development-and-stem-cells/x-chromosome-inactivation The X chromosome is many time larger than the Y chromosome. To compensate for this genetic inequality, female mammalian cells undergo X chromosome inactivation of one X chromosome. Dr. Jeannie Lee explains the how and why of X chromosome inactivation. Talk Overview: Part 1 of 3: In mammals, sex is determined by a pair of unequal sex chromosomes. Genetically male mammals have an X and a Y chromosome while genetically female mammals have two X chromosomes. The X chromosome is many times larger than the Y chromosome. To compensate for this genetic inequality, female mammals undergo X chromosome inactivation in which one of the X chromosomes is randomly chosen to be silenced. X chromosome inactivation has been studied for over 50 years both because it is a physiologically important event and because it is an excellent model for studying epigenetic silencing of genes by long non-coding RNAs. In her first talk, Dr. Jeannie Lee gives an overview of the steps a cell must go through during X inactivation. These include “counting” the X chromosomes, deciding which X chromosome to inactivate, initiating the inactivation and spreading it across the chromosome, and finally maintaining inactivation of the same X chromosome for the rest of the life of the organism. Speaker Biography: Dr. Jeannie Lee is a Professor in the Department of Genetics at Harvard Medical School and in the Department of Molecular Biology at Massachusetts General Hospital (MGH). Her lab uses X chromosome inactivation as a model to study epigenetic regulation by long noncoding RNAs. Lee received her AB in biochemistry and molecular biology from Harvard University and her MD/PhD from the University of Pennsylvania School of Medicine. She was a postdoctoral fellow at the Whitehead Institute and a resident at MGH before joining Harvard/MGH as a faculty member in 1997. Lee was also an HHMI Investigator from 2001-2018. She is a member of the National Academy of Sciences and a Fellow of the American Association for the Advancement of Science. Lee has been honored with numerous awards including the 2016 Centennial Prize from the Genetics Society of America, the 2016 Lurie Prize from the Foundation for the National Institutes of Health, and the 2010 Molecular Biology Award from the National Academy of Sciences. In 2018, she was President of the Genetics Society of America. Learn more about Dr. Lee’s research here: https://www.x-inactivation-lee-lab.org

https://www.ibiology.org/biophysics/lung-surfactant John Clements details the groundbreaking discovery of lung surfactant, which has saved millions of neonatal lives. The expansion of lungs for oxygen exchange is facilitated by lung surfactant. The groundbreaking discovery of this substance was made by Dr. John Clements. In this Discovery Talk, Clements details his scientific journey, touching on his early research, the resistance he encountered in the field, and the discovery of lung surfactant, which has saved millions of neonatal lives. Speaker Biography: John A. Clements graduated from Weill Cornell Medical College in 1947. In 1949, he began service at the Medical Laboratories of the Army Chemical Center in Maryland, where he supervised Army-contracted research on lung physiology. Clements joined the faculty of the UCSF Cardiovascular Research Institute in 1959 and became emeritus faculty there in 2004.

https://www.ibiology.org/cell-biology/protein-sorting Eukaryotic cells have many different membrane-bound organelles with distinct functions and characteristic shapes. How does this happen? Dr. Tom Rapoport explains the important role of protein sorting in determining organelle shape and function. In his first talk, Dr. Tom Rapoport explains that eukaryotic cells contain many membrane-bound organelles each of which has a characteristic shape and distinctive functions that are carried out by specific proteins. Most proteins are made in the cytosol but must move to different cellular destinations. Protein sorting is determined by signal sequences on the proteins that act as “zip codes”. Many proteins sort first to the endoplasmic reticulum (ER) before moving to other intracellular organelles or the plasma membrane. Rapoport explains that as a protein is translated, its signal sequence causes the nascent protein to insert into the Sec61 channel on the ER membrane. The polypeptide segment following the signal sequence will then be translocated across the membrane. Solving the structure of Sec61 channel allowed Rapoport’s lab to understand how proteins, which are typically hydrophilic, can be transported across a lipid membrane. It also helped them determine how Sec 61 differentiates between secreted proteins which need to be released into the ER lumen and transmembrane proteins which need to be anchored in the ER membrane. This improved knowledge of protein sorting helps us to better understand how organelles are formed and how they function. The ER is a vast network that includes different domains with different functions. The rough ER consists of sheets with associated ribosomes and is involved in protein translation. The smooth ER consists of tubules and is important for lipid synthesis and Ca2+ transport. In his second talk, Rapoport explains how his lab identified proteins needed to generate and maintain a tubular ER network. They found two families of proteins that are required to form the high membrane curvature of tubules, and membrane-bound GTPases that fuse the tubules together into a network. The tubule-shaping proteins are also important in forming the edges of the ER sheets. In mammalian cells, however, another set of proteins is required to act as spacers between the membrane sheets. Using ultra-thin section electron microscopy, Rapoport’s lab, in collaboration with others, was able to show that stacked ER sheets are held together by helicoidal membrane connections forming a “parking-garage” like structure. Speaker Biography: Dr. Tom Rapoport has been a Professor of Cell Biology at Harvard Medical School since 1995 and a Howard Hughes Medical Institute Investigator since 1997. Prior to joining Harvard, Rapoport was a Professor at the Institute for Molecular Biology in East Berlin, which later became the Max-Delbrück Institute for Molecular Medicine. Rapoport received his PhD from Humboldt University of Berlin. Rapoport’s research focuses on the understanding how organelles, in particular the endoplasmic reticulum (ER), derives its characteristic shape and performs its specific functions. He has had a long standing interest in how proteins are translocated across organelle membranes. His pioneering research has been recognized with many awards including the Max-Delbrück Medal in 2005, the Sir Hans Kreb Medal in 2007, and the Schleiden Medal in 2011, among many others. Rapoport is a member of the National Academy of Sciences, USA and the German Academy of Sciences, Leopoldina. He is also a Fellow of the American Association for the Advancement of Science (AAAS). Learn more about Rapoport’s research here: http://rapoport.hms.harvard.edu and here: https://www.hhmi.org/scientists/tom-rapoport

https://www.ibiology.org/cell-biology/protein-sorting Eukaryotic cells have many different membrane-bound organelles with distinct functions and characteristic shapes. How does this happen? Dr. Tom Rapoport explains the important role of protein sorting in determining organelle shape and function. In his first talk, Dr. Tom Rapoport explains that eukaryotic cells contain many membrane-bound organelles each of which has a characteristic shape and distinctive functions that are carried out by specific proteins. Most proteins are made in the cytosol but must move to different cellular destinations. Protein sorting is determined by signal sequences on the proteins that act as “zip codes”. Many proteins sort first to the endoplasmic reticulum (ER) before moving to other intracellular organelles or the plasma membrane. Rapoport explains that as a protein is translated, its signal sequence causes the nascent protein to insert into the Sec61 channel on the ER membrane. The polypeptide segment following the signal sequence will then be translocated across the membrane. Solving the structure of Sec61 channel allowed Rapoport’s lab to understand how proteins, which are typically hydrophilic, can be transported across a lipid membrane. It also helped them determine how Sec 61 differentiates between secreted proteins which need to be released into the ER lumen and transmembrane proteins which need to be anchored in the ER membrane. This improved knowledge of protein sorting helps us to better understand how organelles are formed and how they function. The ER is a vast network that includes different domains with different functions. The rough ER consists of sheets with associated ribosomes and is involved in protein translation. The smooth ER consists of tubules and is important for lipid synthesis and Ca2+ transport. In his second talk, Rapoport explains how his lab identified proteins needed to generate and maintain a tubular ER network. They found two families of proteins that are required to form the high membrane curvature of tubules, and membrane-bound GTPases that fuse the tubules together into a network. The tubule-shaping proteins are also important in forming the edges of the ER sheets. In mammalian cells, however, another set of proteins is required to act as spacers between the membrane sheets. Using ultra-thin section electron microscopy, Rapoport’s lab, in collaboration with others, was able to show that stacked ER sheets are held together by helicoidal membrane connections forming a “parking-garage” like structure. Speaker Biography: Dr. Tom Rapoport has been a Professor of Cell Biology at Harvard Medical School since 1995 and a Howard Hughes Medical Institute Investigator since 1997. Prior to joining Harvard, Rapoport was a Professor at the Institute for Molecular Biology in East Berlin, which later became the Max-Delbrück Institute for Molecular Medicine. Rapoport received his PhD from Humboldt University of Berlin. Rapoport’s research focuses on the understanding how organelles, in particular the endoplasmic reticulum (ER), derives its characteristic shape and performs its specific functions. He has had a long standing interest in how proteins are translocated across organelle membranes. His pioneering research has been recognized with many awards including the Max-Delbrück Medal in 2005, the Sir Hans Kreb Medal in 2007, and the Schleiden Medal in 2011, among many others. Rapoport is a member of the National Academy of Sciences, USA and the German Academy of Sciences, Leopoldina. He is also a Fellow of the American Association for the Advancement of Science (AAAS). Learn more about Rapoport’s research here: http://rapoport.hms.harvard.edu and here: https://www.hhmi.org/scientists/tom-rapoport

https://www.ibiology.org/techniques/mass-cytometry How does mass cytometry differ from other types of flow cytometry? When would you choose to use it? How does a mass cytometer work? Dr. Susanne Heck gives an overview of mass cytometry and answers all of these questions. Dr. Susanne Heck begins her talk by explaining why we might choose to use mass cytometry rather than other types of flow cytometry. Traditional flow cytometry is typically limited to the detection of about a dozen parameters in one sample due to overlap between the emission spectra of fluorochromes used to label antibodies. Mass cytometry, on the other hand, allows for the detection of up to 50 parameters in one sample because antibodies are labelled with metal isotopes and separated based on their mass. Heck goes on to explain which metal isotopes are typically used for mass cytometry and why, and she describes how a mass cytometer functions. She finishes by running through an example of using mass cytometry to perform functional phenotyping on human bone marrow cells. Speaker Biography: Dr. Susanne Heck received her PhD in molecular biology from the University of Bremen, Germany, in 1997. After a postdoc in molecular and cellular biology at Albert Einstein College in New York, Heck joined Cellular Genomics Inc., USA, to work on preclinical models for small molecule kinase inhibitors. In 2004, she moved to the Lindsey F. Kimball Research Centre to develop and run the Flow Cytometry Core of the New York Blood Centre. Heck was appointed as head of the NIHR BRC Flow Cytometry Core for Guys and St Thomas Hospital and King’s College London in 2009 and has established a successful human immune monitoring core of international reputation.

https://www.ibiology.org/cell-biology/protein-phosphatases Kinases and phosphatases perform a balancing act in cells by adding and removing phosphate groups from proteins. Dr. Bertolotti shows us that inhibiting specific protein phosphatases can reduce misfolded protein accumulation and reduce neurodegenerative disease. There are many processes and signals in cells that must be turned on and off, sometimes very quickly. How is this done? One important way is via post-translational modification of proteins such as phosphorylation or dephosphorylation. In her first talk, Dr. Anne Bertolotti introduces us to protein phosphatases, the enzymes that remove phosphate from proteins and work in opposition to protein kinases. She gives a brief history of the early experiments that showed that phosphatases are vital to regulating the stability, localization and interactions of many proteins. Bertolotti also describes more recent work demonstrating that protein phosphatases are split enzymes with a catalytic subunit and a subunit that determines substrate specificity. This selective subunit makes phosphatases exquisitely specific and attractive targets for drug development. Bertolotti’s lab has had a long time interest in understanding protein folding and the role of misfolded proteins in neurodegenerative disease. In her second talk, Bertolotti explains how her lab found that selectively inhibiting the dephosphorylation of eIF2⍺, a translation initiation factor, led to a reduction in protein synthesis. Decreasing protein synthesis allowed cells to “catch up” with the degradation of misfolded proteins that may accumulate as a result of cell stress. Her lab went on to show that a selective small molecule phosphatase inhibitor had therapeutic effects in a mouse model of Charcot-Marie-Tooth disease; a disease that results from the accumulation of misfolded protein in the ER. This exciting result suggested that targeted inhibition of protein phosphatases may have therapeutic potential for neurodegenerative diseases. In her third talk, Bertolotti describes a platform developed by her lab that has allowed them to rationally identify selective protein phosphatase inhibitors. Using this platform her lab identified a novel small molecule phosphatase inhibitor that blocks the accumulation of misfolded proteins in the cytosol or nucleus and showed the therapeutic effects of the molecule in a model of Huntington’s disease. Speaker Biography: Dr. Anne Bertolotti’s research focuses on understanding and preventing the deposition of misfolded proteins in cells, a hallmark of numerous neurological diseases. Bertolotti has been a group leader at the MRC Laboratory of Molecular Biology in Cambridge, UK since 2006. Prior to joining the LMB, she was an Associate Professor at Ecole Normale Superieure in Paris from 2001-2006. Bertolotti did her PhD training at the Institute of Genetics and Molecular and Cellular Biology (IGBMC) near Strasbourg, France and she was a post-doctoral fellow at the Skirball Institute of Biomolecular Medicine at NYU School of Medicine in New York. Bertolotti was elected an EMBO Young Investigator in 2005 and an EMBO member in 2013. In 2014, she was awarded the Hooke Medal of the British Society for Cell Biology for her contributions to our understanding of abnormal protein folding. Bertolotti was elected a Fellow of the UK Academy of Medical Sciences in 2017. Learn more about Bertolotti’s research here: https://www2.mrc-lmb.cam.ac.uk/group-leaders/a-to-g/anne-bertolotti

https://www.ibiology.org/cell-biology/protein-phosphatases Kinases and phosphatases perform a balancing act in cells by adding and removing phosphate groups from proteins. Dr. Bertolotti shows us that inhibiting specific protein phosphatases can reduce misfolded protein accumulation and reduce neurodegenerative disease. There are many processes and signals in cells that must be turned on and off, sometimes very quickly. How is this done? One important way is via post-translational modification of proteins such as phosphorylation or dephosphorylation. In her first talk, Dr. Anne Bertolotti introduces us to protein phosphatases, the enzymes that remove phosphate from proteins and work in opposition to protein kinases. She gives a brief history of the early experiments that showed that phosphatases are vital to regulating the stability, localization and interactions of many proteins. Bertolotti also describes more recent work demonstrating that protein phosphatases are split enzymes with a catalytic subunit and a subunit that determines substrate specificity. This selective subunit makes phosphatases exquisitely specific and attractive targets for drug development. Bertolotti’s lab has had a long time interest in understanding protein folding and the role of misfolded proteins in neurodegenerative disease. In her second talk, Bertolotti explains how her lab found that selectively inhibiting the dephosphorylation of eIF2⍺, a translation initiation factor, led to a reduction in protein synthesis. Decreasing protein synthesis allowed cells to “catch up” with the degradation of misfolded proteins that may accumulate as a result of cell stress. Her lab went on to show that a selective small molecule phosphatase inhibitor had therapeutic effects in a mouse model of Charcot-Marie-Tooth disease; a disease that results from the accumulation of misfolded protein in the ER. This exciting result suggested that targeted inhibition of protein phosphatases may have therapeutic potential for neurodegenerative diseases. In her third talk, Bertolotti describes a platform developed by her lab that has allowed them to rationally identify selective protein phosphatase inhibitors. Using this platform her lab identified a novel small molecule phosphatase inhibitor that blocks the accumulation of misfolded proteins in the cytosol or nucleus and showed the therapeutic effects of the molecule in a model of Huntington’s disease. Speaker Biography: Dr. Anne Bertolotti’s research focuses on understanding and preventing the deposition of misfolded proteins in cells, a hallmark of numerous neurological diseases. Bertolotti has been a group leader at the MRC Laboratory of Molecular Biology in Cambridge, UK since 2006. Prior to joining the LMB, she was an Associate Professor at Ecole Normale Superieure in Paris from 2001-2006. Bertolotti did her PhD training at the Institute of Genetics and Molecular and Cellular Biology (IGBMC) near Strasbourg, France and she was a post-doctoral fellow at the Skirball Institute of Biomolecular Medicine at NYU School of Medicine in New York. Bertolotti was elected an EMBO Young Investigator in 2005 and an EMBO member in 2013. In 2014, she was awarded the Hooke Medal of the British Society for Cell Biology for her contributions to our understanding of abnormal protein folding. Bertolotti was elected a Fellow of the UK Academy of Medical Sciences in 2017. Learn more about Bertolotti’s research here: https://www2.mrc-lmb.cam.ac.uk/group-leaders/a-to-g/anne-bertolotti

https://www.ibiology.org/cell-biology/protein-phosphatases Kinases and phosphatases perform a balancing act in cells by adding and removing phosphate groups from proteins. Dr. Bertolotti shows us that inhibiting specific protein phosphatases can reduce misfolded protein accumulation and reduce neurodegenerative disease. There are many processes and signals in cells that must be turned on and off, sometimes very quickly. How is this done? One important way is via post-translational modification of proteins such as phosphorylation or dephosphorylation. In her first talk, Dr. Anne Bertolotti introduces us to protein phosphatases, the enzymes that remove phosphate from proteins and work in opposition to protein kinases. She gives a brief history of the early experiments that showed that phosphatases are vital to regulating the stability, localization and interactions of many proteins. Bertolotti also describes more recent work demonstrating that protein phosphatases are split enzymes with a catalytic subunit and a subunit that determines substrate specificity. This selective subunit makes phosphatases exquisitely specific and attractive targets for drug development. Bertolotti’s lab has had a long time interest in understanding protein folding and the role of misfolded proteins in neurodegenerative disease. In her second talk, Bertolotti explains how her lab found that selectively inhibiting the dephosphorylation of eIF2⍺, a translation initiation factor, led to a reduction in protein synthesis. Decreasing protein synthesis allowed cells to “catch up” with the degradation of misfolded proteins that may accumulate as a result of cell stress. Her lab went on to show that a selective small molecule phosphatase inhibitor had therapeutic effects in a mouse model of Charcot-Marie-Tooth disease; a disease that results from the accumulation of misfolded protein in the ER. This exciting result suggested that targeted inhibition of protein phosphatases may have therapeutic potential for neurodegenerative diseases. In her third talk, Bertolotti describes a platform developed by her lab that has allowed them to rationally identify selective protein phosphatase inhibitors. Using this platform her lab identified a novel small molecule phosphatase inhibitor that blocks the accumulation of misfolded proteins in the cytosol or nucleus and showed the therapeutic effects of the molecule in a model of Huntington’s disease. Speaker Biography: Dr. Anne Bertolotti’s research focuses on understanding and preventing the deposition of misfolded proteins in cells, a hallmark of numerous neurological diseases. Bertolotti has been a group leader at the MRC Laboratory of Molecular Biology in Cambridge, UK since 2006. Prior to joining the LMB, she was an Associate Professor at Ecole Normale Superieure in Paris from 2001-2006. Bertolotti did her PhD training at the Institute of Genetics and Molecular and Cellular Biology (IGBMC) near Strasbourg, France and she was a post-doctoral fellow at the Skirball Institute of Biomolecular Medicine at NYU School of Medicine in New York. Bertolotti was elected an EMBO Young Investigator in 2005 and an EMBO member in 2013. In 2014, she was awarded the Hooke Medal of the British Society for Cell Biology for her contributions to our understanding of abnormal protein folding. Bertolotti was elected a Fellow of the UK Academy of Medical Sciences in 2017. Learn more about Bertolotti’s research here: https://www2.mrc-lmb.cam.ac.uk/group-leaders/a-to-g/anne-bertolotti

https://www.ibiology.org/cell-biology/membrane-contact-sites The endoplasmic reticulum (ER) is a dynamic network of tubules that reaches throughout a cell. It interacts with other organelles at membrane contact sites. As Dr. Gia Voeltz explains, these sites are critical for Ca2+ regulation, lipid transport and defining sites of division for endosomes and other organelles. Many of us are used to seeing cartoons of cells with organelles shown as static, isolated structures. The endoplasmic reticulum is often shown looking like a stack of pancakes pushed up against the nuclear envelope. In her first talk, Dr. Gia Voeltz explains that recent advances in light microscopy have given us a very different view of organelles and their interactions. The ER is, in fact, an expansive, and highly dynamic, network of tubules that spreads throughout the cell. It interacts with other organelles such as the plasma membrane, endosomes, and mitochondria at points called membrane contact sites. Using beautiful fluorescent images and movies, Voeltz shows us that these ER membrane contact sites are important for many functions such as trafficking lipids and Ca2+ and determining where mitochondria divide and endosomes undergo fission. These exciting findings define a new cellular function for the ER. In her second lecture, Voeltz explains how her lab used a BioID strategy to identify some of the proteins found at membrane contact sites between the ER and endosomes; a difficult task given the transient nature of contact sites. They were able to identify a number of proteins responsible for marking the timing and location of endosome fission and for recruiting the ER to the bud. Depleting these proteins blocked cargo sorting to the Golgi. Voeltz’ lab is now working to determine how much of this machinery is conserved in processes such as the mitochondrial division. Speaker Biography: Dr. Gia Voeltz discovered her love for research as an undergraduate student at the University of California Santa Cruz. After graduation, she moved east to Yale University where she was a graduate student with Joan Steitz and studied RNA processing in Xenopus extracts. As a post-doctoral fellow in Tom Rapoport’s lab at Harvard, Voeltz tackled the question of how organelles, and in particular the endoplasmic reticulum, are shaped. Voeltz started her own lab at the University of Colorado, Boulder in 2006. She became an HHMI Faculty Scholar in 2016 and an HHMI Investigator in 2018. Her lab investigates how the ER interacts with other organelles such as the mitochondria and endosomes via membrane contact sites and how these contact sites may regulate organelle division and function. Learn more about Voeltz’ research here: https://www.voeltzlab.org

https://www.ibiology.org/cell-biology/membrane-contact-sites The endoplasmic reticulum (ER) is a dynamic network of tubules that reaches throughout a cell. It interacts with other organelles at membrane contact sites. As Dr. Gia Voeltz explains, these sites are critical for Ca2+ regulation, lipid transport and defining sites of division for endosomes and other organelles. Many of us are used to seeing cartoons of cells with organelles shown as static, isolated structures. The endoplasmic reticulum is often shown looking like a stack of pancakes pushed up against the nuclear envelope. In her first talk, Dr. Gia Voeltz explains that recent advances in light microscopy have given us a very different view of organelles and their interactions. The ER is, in fact, an expansive, and highly dynamic, network of tubules that spreads throughout the cell. It interacts with other organelles such as the plasma membrane, endosomes, and mitochondria at points called membrane contact sites. Using beautiful fluorescent images and movies, Voeltz shows us that these ER membrane contact sites are important for many functions such as trafficking lipids and Ca2+ and determining where mitochondria divide and endosomes undergo fission. These exciting findings define a new cellular function for the ER. In her second lecture, Voeltz explains how her lab used a BioID strategy to identify some of the proteins found at membrane contact sites between the ER and endosomes; a difficult task given the transient nature of contact sites. They were able to identify a number of proteins responsible for marking the timing and location of endosome fission and for recruiting the ER to the bud. Depleting these proteins blocked cargo sorting to the Golgi. Voeltz’ lab is now working to determine how much of this machinery is conserved in processes such as the mitochondrial division. Speaker Biography: Dr. Gia Voeltz discovered her love for research as an undergraduate student at the University of California Santa Cruz. After graduation, she moved east to Yale University where she was a graduate student with Joan Steitz and studied RNA processing in Xenopus extracts. As a post-doctoral fellow in Tom Rapoport’s lab at Harvard, Voeltz tackled the question of how organelles, and in particular the endoplasmic reticulum, are shaped. Voeltz started her own lab at the University of Colorado, Boulder in 2006. She became an HHMI Faculty Scholar in 2016 and an HHMI Investigator in 2018. Her lab investigates how the ER interacts with other organelles such as the mitochondria and endosomes via membrane contact sites and how these contact sites may regulate organelle division and function. Learn more about Voeltz’ research here: https://www.voeltzlab.org

https://www.ibiology.org/immunology/xenotransplantation Megan Sykes provides an introduction to the field of organ transplantation, discusses the immunological responses associated with this procedure, and explains the new onsets of xenotransplantation. Talk Overview: Dr. Megan Sykes provides an introduction to the field of organ transplantation and discusses the immunological responses associated with this procedure. Rejection is a major limitation to the success of transplantation. Sykes explains what causes rejection episodes in different types of transplantation, and outlines what we can do to prevent this from happening. As Sykes explains, the Holy grail of transplantation is tolerance, the long-term graft acceptance without the long-term use of immunosuppressants. Sykes and collaborators developed a hematopoietic cell transplantation and mixed chimerism technique that proved to induce true tolerance in humans. They showed that transient mixed chimerism, the co-existence of donor and recipient hematopoietic elements, was detected in patients where tolerance was observed. Sykes reviews the clinical trial results and explains the experimental techniques used to study the molecular features that predict tolerance and low rates of organ rejection in patients. In her third lecture, Sykes provides an overview of xenotransplantation, the use of organs or grafts from other (non-human) species. She outlines the challenges encountered with cross-species transplantation, and how scientist have been able to overcome these difficulties. Sykes and other laboratories are exploring the use of miniature pigs for xenotransplantations to humans. Sykes shows the outcome of xenotransplantations performed between different species (e.g. rat to mouse or pig to baboon), and what scientists have learned from these results. Speaker Biography: Dr. Megan Sykes is the Friedlander Professor of Medicine, a Professor of Microbiology and Immunology and a Professor of Surgical Sciences at Columbia University Medical Center, and the director of the Columbia Center for Translational Immunology. In 1982, Sykes completed her medical degree at University of Toronto and continued her medical training in Montreal and Toronto. In 1990, she joined the faculty of Massachusetts General Hospital and Harvard Medical School, where she pioneered studies to induce mixed chimerism and tolerance after organ transplantation in humans. In 2010, she moved her lab to Columbia University where she established the Columbia Center for Translational Immunology and continues her research innovating techniques in the field of allo- and xenotransplantation. For her scientific contributions, Sykes was elected member of the National Academy of Medicine (2009) and a Fellow of the AAAS (2009). Learn more about Sykes’ research at her lab website. http://www.microbiology.columbia.edu/faculty/sykes.html

https://www.ibiology.org/immunology/xenotransplantation Megan Sykes provides an introduction to the field of organ transplantation, discusses the immunological responses associated with this procedure, and explains the new onsets of xenotransplantation. Talk Overview: Dr. Megan Sykes provides an introduction to the field of organ transplantation and discusses the immunological responses associated with this procedure. Rejection is a major limitation to the success of transplantation. Sykes explains what causes rejection episodes in different types of transplantation, and outlines what we can do to prevent this from happening. As Sykes explains, the Holy grail of transplantation is tolerance, the long-term graft acceptance without the long-term use of immunosuppressants. Sykes and collaborators developed a hematopoietic cell transplantation and mixed chimerism technique that proved to induce true tolerance in humans. They showed that transient mixed chimerism, the co-existence of donor and recipient hematopoietic elements, was detected in patients where tolerance was observed. Sykes reviews the clinical trial results and explains the experimental techniques used to study the molecular features that predict tolerance and low rates of organ rejection in patients. In her third lecture, Sykes provides an overview of xenotransplantation, the use of organs or grafts from other (non-human) species. She outlines the challenges encountered with cross-species transplantation, and how scientist have been able to overcome these difficulties. Sykes and other laboratories are exploring the use of miniature pigs for xenotransplantations to humans. Sykes shows the outcome of xenotransplantations performed between different species (e.g. rat to mouse or pig to baboon), and what scientists have learned from these results. Speaker Biography: Dr. Megan Sykes is the Friedlander Professor of Medicine, a Professor of Microbiology and Immunology and a Professor of Surgical Sciences at Columbia University Medical Center, and the director of the Columbia Center for Translational Immunology. In 1982, Sykes completed her medical degree at University of Toronto and continued her medical training in Montreal and Toronto. In 1990, she joined the faculty of Massachusetts General Hospital and Harvard Medical School, where she pioneered studies to induce mixed chimerism and tolerance after organ transplantation in humans. In 2010, she moved her lab to Columbia University where she established the Columbia Center for Translational Immunology and continues her research innovating techniques in the field of allo- and xenotransplantation. For her scientific contributions, Sykes was elected member of the National Academy of Medicine (2009) and a Fellow of the AAAS (2009). Learn more about Sykes’ research at her lab website. http://www.microbiology.columbia.edu/faculty/sykes.html

https://www.ibiology.org/immunology/xenotransplantation Megan Sykes provides an introduction to the field of organ transplantation, discusses the immunological responses associated with this procedure, and explains the new onsets of xenotransplantation. Talk Overview: Dr. Megan Sykes provides an introduction to the field of organ transplantation and discusses the immunological responses associated with this procedure. Rejection is a major limitation to the success of transplantation. Sykes explains what causes rejection episodes in different types of transplantation, and outlines what we can do to prevent this from happening. As Sykes explains, the Holy grail of transplantation is tolerance, the long-term graft acceptance without the long-term use of immunosuppressants. Sykes and collaborators developed a hematopoietic cell transplantation and mixed chimerism technique that proved to induce true tolerance in humans. They showed that transient mixed chimerism, the co-existence of donor and recipient hematopoietic elements, was detected in patients where tolerance was observed. Sykes reviews the clinical trial results and explains the experimental techniques used to study the molecular features that predict tolerance and low rates of organ rejection in patients. In her third lecture, Sykes provides an overview of xenotransplantation, the use of organs or grafts from other (non-human) species. She outlines the challenges encountered with cross-species transplantation, and how scientist have been able to overcome these difficulties. Sykes and other laboratories are exploring the use of miniature pigs for xenotransplantations to humans. Sykes shows the outcome of xenotransplantations performed between different species (e.g. rat to mouse or pig to baboon), and what scientists have learned from these results. Speaker Biography: Dr. Megan Sykes is the Friedlander Professor of Medicine, a Professor of Microbiology and Immunology and a Professor of Surgical Sciences at Columbia University Medical Center, and the director of the Columbia Center for Translational Immunology. In 1982, Sykes completed her medical degree at University of Toronto and continued her medical training in Montreal and Toronto. In 1990, she joined the faculty of Massachusetts General Hospital and Harvard Medical School, where she pioneered studies to induce mixed chimerism and tolerance after organ transplantation in humans. In 2010, she moved her lab to Columbia University where she established the Columbia Center for Translational Immunology and continues her research innovating techniques in the field of allo- and xenotransplantation. For her scientific contributions, Sykes was elected member of the National Academy of Medicine (2009) and a Fellow of the AAAS (2009). Learn more about Sykes’ research at her lab website. http://www.microbiology.columbia.edu/faculty/sykes.html

https://www.ibiology.org/immunology/th17 Th17 cells are important in our protective immune response to bacteria and fungi. They also can exist, however, in a pathogenic form that causes autoimmune disease. In his first lecture, Dan Littman discusses the opposing roles of Th17 cells. They protect mucosal surfaces from infection with bacteria and fungi, but they can also cause autoimmune inflammation. Using a mouse model of autoimmunity called experimental autoimmune encephalitis (EAE), Littman and his lab have shown that there are two types of Th17 cells. Non-pathogenic Th17 cells are induced by the microbiota and protect barrier surfaces, while pathogenic Th17 cells are induced by the presence of IL-23, likely the result of inflammation elsewhere in the body. Both types Th17 cells secrete the cytokines IL-17A, IL-17F and IL-22, however, pathogenic Th17 cells also secrete interferon gamma (IFNγ) which induces further inflammation and autoimmune disease. In the last 10 years, several classes of innate lymphoid cells have been found to share similar cytokine profiles to Th17 cells and these cells appear to be another important layer in protecting surfaces in the gut and lung from infection. In his second talk, Littman explains that different commensal microbes in our gut elicit different T cell responses - either pathogenic or non-pathogenic. His lab is beginning to identify the pathogens and decipher the pathways that determines the host T cell response. This research has important clinical relevance since a cancer patient’s microbiota may help determine their response to chemotherapy. Microbiota that induce non-pathogenic Th17 cells are protective against autoimmunity but may decrease anti-tumor immunity, while microbiota that contribute to autoimmunity may enhance anti-tumor T cell responses. Speaker Biography: Dan Littman is the Helen and Martin Kimmel Professor of Molecular Immunology in the Department of Pathology and a professor in the Department of Microbiology at the Skirball Institute of Biomolecular Medicine of New York University School of Medicine. He is also an Investigator of the Howard Hughes Medical Institute. Littman discovered the excitement of science while he was an undergraduate student at Princeton University. He went on to receive his M.D. and Ph.D. from Washington University in St. Louis. As post-doc in Richard Axel’s lab at Columbia University, Littman isolated the genes for CD8 and CD4, molecules involved in T lymphocyte development. Littman then joined the faculty of the University of California, San Francisco where he was one of the first scientists to recognize that HIV infects T helper cells by binding to CD4. Since 1995, Littman has been based at NYU. Littman’s lab has continued to study the development and differentiation of T lymphocytes. They are interested in understanding how a normal protective immune response differs from a pathogenic response such as that found in inflammation and autoimmune disease. Currently, they are also investigating the importance of the microbiome in influencing immunity. Littman is a member of the National Academy of Sciences and a fellow of the American Academy of Arts and Science and the American Academy of Microbiology. His groundbreaking work has been recognized with many prizes including the 2004 New York City Mayor’s Award for Excellence in Science and Technology, the 2013 Ross Prize in Molecular Medicine, and the 2016 Vilcek Prize in Biomedical Science amongst others. Learn more about Littman’s research here: https://med.nyu.edu/skirball-lab/littmanlab/Home.html

https://www.ibiology.org/immunology/th17 Th17 cells are important in our protective immune response to bacteria and fungi. They also can exist, however, in a pathogenic form that causes autoimmune disease. In his first lecture, Dan Littman discusses the opposing roles of Th17 cells. They protect mucosal surfaces from infection with bacteria and fungi, but they can also cause autoimmune inflammation. Using a mouse model of autoimmunity called experimental autoimmune encephalitis (EAE), Littman and his lab have shown that there are two types of Th17 cells. Non-pathogenic Th17 cells are induced by the microbiota and protect barrier surfaces, while pathogenic Th17 cells are induced by the presence of IL-23, likely the result of inflammation elsewhere in the body. Both types Th17 cells secrete the cytokines IL-17A, IL-17F and IL-22, however, pathogenic Th17 cells also secrete interferon gamma (IFNγ) which induces further inflammation and autoimmune disease. In the last 10 years, several classes of innate lymphoid cells have been found to share similar cytokine profiles to Th17 cells and these cells appear to be another important layer in protecting surfaces in the gut and lung from infection. In his second talk, Littman explains that different commensal microbes in our gut elicit different T cell responses - either pathogenic or non-pathogenic. His lab is beginning to identify the pathogens and decipher the pathways that determines the host T cell response. This research has important clinical relevance since a cancer patient’s microbiota may help determine their response to chemotherapy. Microbiota that induce non-pathogenic Th17 cells are protective against autoimmunity but may decrease anti-tumor immunity, while microbiota that contribute to autoimmunity may enhance anti-tumor T cell responses. Speaker Biography: Dan Littman is the Helen and Martin Kimmel Professor of Molecular Immunology in the Department of Pathology and a professor in the Department of Microbiology at the Skirball Institute of Biomolecular Medicine of New York University School of Medicine. He is also an Investigator of the Howard Hughes Medical Institute. Littman discovered the excitement of science while he was an undergraduate student at Princeton University. He went on to receive his M.D. and Ph.D. from Washington University in St. Louis. As post-doc in Richard Axel’s lab at Columbia University, Littman isolated the genes for CD8 and CD4, molecules involved in T lymphocyte development. Littman then joined the faculty of the University of California, San Francisco where he was one of the first scientists to recognize that HIV infects T helper cells by binding to CD4. Since 1995, Littman has been based at NYU. Littman’s lab has continued to study the development and differentiation of T lymphocytes. They are interested in understanding how a normal protective immune response differs from a pathogenic response such as that found in inflammation and autoimmune disease. Currently, they are also investigating the importance of the microbiome in influencing immunity. Littman is a member of the National Academy of Sciences and a fellow of the American Academy of Arts and Science and the American Academy of Microbiology. His groundbreaking work has been recognized with many prizes including the 2004 New York City Mayor’s Award for Excellence in Science and Technology, the 2013 Ross Prize in Molecular Medicine, and the 2016 Vilcek Prize in Biomedical Science amongst others. Learn more about Littman’s research here: https://med.nyu.edu/skirball-lab/littmanlab/Home.html

https://www.ibiology.org/immunology/cells-immune-system Brittany Anderton provides an overview of the major cells of the human immune system. The immune system is responsible for fighting infection and disease. It is comprised of many specialized cell types, all which work together to keep people healthy. In this short video, Dr. Brittany Anderton introduces the cells of the immune system. She compares and contrasts innate and adaptive immunity, and lays out the molecular interactions required to activate each type of response. Speaker Biography: Dr. Brittany Anderton obtained her PhD in biomedicine from UCSF in 2015. After that, she did a non-traditional postdoc at UC Davis where she studied the teaching and communication of biotechnology. Brittany has served as adjunct faculty at UC Davis and CSU Sacramento, where she taught introductory biology courses. At iBiology, she seeks to improve the teaching and communication of science using evidence from the learning and social sciences.

Tobias Erb outlines the principles of building synthetic metabolism using, as an example, work in his lab to engineer bacteria to undergo synthetic carbon dioxide fixation. https://www.ibiology.org/bioengineering/synthetic-carbon-dioxide-fixation/ Talk Overview: The conversion of atmospheric carbon dioxide (CO2) to biomass via photosynthesis is the foundation for all of our food and energy. Tobias Erb explains how his lab is working to design, build and optimize pathways for synthetic CO2 fixation. By combining enzymes from multiple organisms with “re-engineered” enzymes and optimizing the processes, Erb and his lab generated a synthetic cycle that fixes CO2 more energy efficiently than photosynthesis. In the future, they plan to test the system in artificial cells and to transplant it into bacteria and chloroplasts.  The video exemplifies the general rules and principles of building synthetic metabolism. Speaker Biography: Tobias Erb studied biology and chemistry at the University of Freiburg and Ohio State University. He was a postdoctoral fellow at the University of Illinois before starting his own group at the Swiss Federal Institute of Technology (ETH) in Zurich, Switzerland.  In 2014, Erb moved to the Max Planck Institute for Terrestrial Microbiology in Marburg, Germany where he became Director and Head of the Department of Biochemistry and Synthetic Metabolism in 2017. Erb’s lab studies the principles of natural metabolism with the aim of using this knowledge to build, from basics, novel synthetic metabolic processes.  Erb is particularly interested in the enzymes and pathways of bacteria that capture and convert carbon dioxide. In 2015, Erb was named one of 12 up-and-coming-scientists by the American Chemical Society and in 2016 he received the Heinz-Maier-Leibniz prize of the German Research Foundation.   Learn more about Erb’s research here: http://www.mpi-marburg.mpg.de/erb

David Bikard’s talk focuses on engineering bacteria with CRISPR to combat microbial pathogens.  He explains how CRISPR technologies could eliminate antibiotic resistance. https://www.ibiology.org/bioengineering/engineering-bacteria-crispr/ Talk Overview: Dr. David Bikard’s lab focuses on engineering bacteria with CRISPR to combat microbial pathogens. In this video, he introduces the historical context for using CRISPR in bacteria and then delves into two CRISPR technologies being developed by his lab. Part of his lab is using CRISPR/Cas9 to eliminate antibiotic resistance in bacterial populations. His group is also optimizing a catalytically dead Cas9 (dCas9) to modulate levels of CRISPR-induced transcriptional repression and use it in pooled high throughput screens for gene function. Speaker Biography: Dr. David Bikard is the head of the Synthetic Biology Group at the Institut Pasteur in Paris, France. Originally trained in engineering at AgroParisTech, he later received his Masters and PhD from Paris Diderot University for his work with the Institut Pasteur on the intergron bacterial recombination system. He began working with CRISPR during his postdoctoral fellowship with Dr. Luciano Marraffini at Rockefeller University. His work led to him becoming the founder and CSO of the company Eligo Biosciences. In 2014, he returned to the Institut Pasteur as an Investigator in Microbiology. More information about David Bikard’s work can be found on his lab website: https://research.pasteur.fr/en/team/synthetic-biology/