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The Gill Center for Biomolecular Science

Gill Seminars

Previous Speakers

Upcoming Speakers

July 29, 2016
Baptiste Lacoste, Ph.D.

The Ottawa Hospital Research Institute, Neuroscience Program
University of Ottawa Brain and Mind Research Institute
Faculty of Medicine, Department of Cellular and Molecular Medicine

Seminar will be held in Multidisciplinary Science Building II (MSBII), Room 102 at 12:00 p.m.

Title: Pending

Abstract: Pending

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September 12, 2016
Ben Barres, M.D., Ph.D.

Stanford University School of Medicine

Seminar will take place in the Indiana Memorial Union, Whittenberger Auditorium during the
2016 Gill Symposium.

Title: What do reactive astrocytes do?

Authors: S. A. Liddelow, L. E. Clarke, B. A. Barres
Department of Neurobiology, Stanford University, Stanford, CA

Abstract: Astrocytes undergo profound changes in morphology and gene expression in response to brain injury and disease. But whether reactive astrocytes are harmful or helpful has been unclear. We recently found that the genes induced in reactive astrocytes depends on the nature of the inducing injury. After ischemia, reactive astrocytes upregulate neurotrophic factors suggesting they may be beneficial, whereas after systemic injection of lipopolysaccharide (LPS) they strongly upregulate multiple complement cascade components needed to drive synapse destruction suggesting they may be detrimental. These findings suggest that, like macrophages which exist on a spectrum from bad (M1) to good (M2) states, reactive astrocytes also exist in bad (A1) and good (A2) states. Here we show that LPS-induced M1 microglia are sufficient to induce A1 reactive astrocytes. M1 microglia do this by releasing IL1α, TNFα and C1q, which together are sufficient to induce A1 (bad) reactivity in purified astrocytes within 24h and are all required for M1 microglia to induce the A1 state. Using IL1α, TNFα and C1q together, allowed us to create the first defined serum-free cultures of pure A1 reactive astrocytes enabling us to investigate their function. By directly comparing the function of normal astrocytes with A1 astrocytes in vitro, we found that A1 astrocytes are unable to promote neuronal survival, axon outgrowth, synapse formation or synapse function, and have lost the ability to phagocytose synaptosomes and myelin debris. In addition to loss of their normal functions, A1 reactive astrocytes gained a powerfully neurotoxic function, releasing a toxic protein that specifically induces apoptosis of neurons and oligodendrocytes. Drugs that prevent the formation of A1 reactive astrocytes or inhibit this toxic protein may have great potential to treat neurodegenerative diseases and promote regeneration after spinal cord injury.

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September 12, 2016
Beth Stevens, Ph.D.

Assistant Professor of Neurology
FM Kirby Neurobiology Center
Boston Children's Hospital
Harvard Medical School
Broad Institute

Seminar will take place in the Indiana Memorial Union, Whittenberger Auditorium during the
2016 Gill Symposium.

Title: Immune Mechanisms of Synapse Loss in Health and Disease

Abstract: One of the major unsolved mysteries in neuroscience is how synapses are eliminated in the healthy and diseased brain. During development, neural circuitry undergoes a remodeling process in which excess synapses are eliminated and the remaining synapses are strengthened. This pruning process is required for precise brain wiring; however the mechanisms that drive the elimination of specific synapses in the brain remain unclear. Emerging evidence from several model systems implicate molecules traditionally associated with the adaptive and innate immune system. For example, recent work from our laboratory revealed a key role for microglia and molecules traditionally associated the classical complement cascade in developmental synaptic pruning.  Our recent studies support a model in which ‘weaker’ or less active synapses in the developing brain are targeted by complement proteins (C1q, C3) and then eliminated by phagocytic microglia that express receptors for complement and other immune molecules. These findings raise the question of how microglia differentiate the synapses or axons to prune from those to leave intact. Microglia-mediated synaptic refinement appears to depend on a careful balance of “eat me”  (ie. complement) and a group of novel immune- related protective signals.
An early hallmark of many neurodegenerative diseases (NDDs) is a progressive, region-specific degeneration of synapses.  Our recent work suggest that aberrant activation of some of these normal immune –related pruning pathways mediate early synapse loss in neurodegenerative diseases (NDDs), including Alzheimer’s Disease (AD) and Huntington’s disease (HD). Thus, understanding how these immune mechanisms drive developmental pruning may provide novel insight into how to protect synapses in NDDS and other disorders of synaptic dysfunction, including autism and schizophrenia.

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September 12, 2016
Nicola Allen, Ph.D.

Salk Institute for Biological Studies

Seminar will take place in the Indiana Memorial Union, Whittenberger Auditorium during the
2016 Gill Symposium.

Title: Astrocyte regulation of neuronal glutamate receptors

Abstract: Neuronal synapses are essential points of information transfer within neuronal circuits, and the correct formation and maturation of synapses is necessary for the brain to function throughout life. Astrocytes are the most abundant cell type in the brain, and many synapses have an astrocyte process associated with them. Astrocytes secrete factors that regulate the formation of excitatory glutamatergic synapses, including factors that increase the number of synaptic AMPA glutamate receptors (AMPARs). The levels of AMPARs at a synapse determine the size of the synaptic response, and the regulated addition and removal of AMPARs at synaptic sites is the molecular mechanism underlying learning and memory. AMPARs are tetramers and there are four subunits, GluA1-4, and functional receptors are composed of combinations of these e.g. GluA1 homomers or GluA2/3 heteromers. The functional properties of the AMPAR are determined by its subunit composition, for example the presence of the GluA2 subunit makes the channels impermeable to calcium, whilst GluA1 homomers are calcium permeable. We found that astrocytes secrete factors that increase the surface levels and synaptic accumulation of all AMPAR subunits in neurons by three-fold, thus strongly regulating neuronal activity. We identified the astrocyte-secreted proteins, glypican 4 and 6 (Gpc4 and 6), as sufficient to increase both the frequency and amplitude of glutamatergic synaptic transmission by recruiting the GluA1 subunit of the AMPAR to synaptic sites. These studies showed that Gpc4 specifically regulates GluA1 AMPARs, and that there are additional unknown astrocyte-derived signals that regulate the trafficking of other AMPA receptor subunits, i.e. GluA2/3 and GluA4. I will present data on our ongoing work to a) determine how Gpc4 recruits GluA1 to synapses, b) determine what regulates the expression and release of Gpc4 from astrocytes, c) determine the contribution of astrocyte-enriched glypican family members to synapse formation and function in vivo, d) identify the astrocyte-secreted factor that regulates GluA2 recruitment to synapses. Identifying the mechanisms that astrocytes use to regulate synaptic AMPARs has important implications for understanding how synaptic strength is normally regulated during development, how it is altered during learning and memory, and how it can be misregulated in neurological disorders such as autism and schizophrenia.

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September 12, 2016
Richard Daneman, Ph.D.

University of California, San Diego

Seminar will take place in the Indiana Memorial Union, Whittenberger Auditorium during the
2016 Gill Symposium.

Title: The Blood-Brain Barrier in Health and Disease

Abstract: Vascular endothelial cells in the central nervous system (CNS) form a barrier that restricts the movement of molecules and ions between the blood and the brain.  This blood-brain barrier (BBB) is crucial to ensure proper neuronal function and protect the CNS from injury and disease.  Although the properties of the BBB are manifested in the endothelial cells, transplantation studies have demonstrated that the BBB is not intrinsic to the endothelial cells, but is induced by interactions with the neural cells.  Here we use a genomic, genetic and molecular approach to elucidate the cellular and molecular mechanisms that regulate the formation and function of the BBB.   We have identified a critical role for pericytes in regulating the permeability of CNS vessels by inhibiting the properties that make endothelial cells leaky. In particular pericytes limit the rate of transcytosis through endothelial cells as well as the expression of leukocyte adhesion molecules in CNS endothelial cells, which limits CNS immune infiltration. Furthermore, we have developed methods to highly purify and gene profile endothelial cells from different tissues, and by comparing the transcriptional profile of brain endothelial cells with those purified from the liver and lung, we have generated a comprehensive resource of transcripts that are specific to the BBB forming endothelial cells of the brain.    We have further examined the profile of CNS endothelial cells following injury and disease and have identified molecular mechanisms by which pericytes control BBB formation, which are then disrupted during neurological disease leading to BBB dysfunction. 

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September 12, 2016
Cagla Eroglu, Ph.D.

Duke University Medical Center

Seminar will take place in the Indiana Memorial Union, Whittenberger Auditorium during the
2016 Gill Symposium.

Title: Pending

Abstract: Pending

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October 3, 2016
Andrew Holmes, Ph.D.

National Institutes of Health, National Institute on Alcohol and Abuse and Alcoholism

Seminar will be held in Psychology, Room 101 at 4:00 p.m.

Title: Pending

Abstract: Pending

Co-sponsored with Program in Neuroscience

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October 10, 2016
Gregor Eichele, Ph.D.

Max Planck Institute for Biophysical Chemistry

Seminar will be held in Psychology, Room 101 at 4:00 p.m.

Title: Active matter: intertwined cilia domains orchestrate complex fluid flow in the mammalian brain

Abstract: Cerebrospinal fluid (CSF) conveys many physiologically important signaling factors through the ventricular cavities of the brain. We investigated the transport of CSF in the third ventricle of the mouse and rat and discovered a highly organized pattern of cilia modules collectively giving rise to a network of fluid flows that allows for precise transport and cargo delivery within this ventricle. We also discovered a cilia-based switch that periodically alters the flow pattern so as to create a dynamic subdivision that may control cargo distribution in the third ventricle. Our work suggests that ciliated epithelia sustain hydrodynamic regulation of transport of CSF components

Co-sponsored with Program in Neuroscience

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January 30, 2017
Michal Schwartz, Ph.D.

Weizmann Institute of Science

Seminar will be held in Psychology, Room 101 at 4:00 p.m.

Title: Pending

Abstract: Pending

Co-sponsored with Program in Neuroscience

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February 27, 2017
Matthew N. Rasband, Ph.D.

Baylor College of Medicine

Seminar will be held in Psychology, Room 101 at 4:00 p.m.

Title: Pending

Abstract: Pending

Co-sponsored with Program in Neuroscience

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