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The Gill Center for Biomolecular Science

Gill Seminars

Previous Speakers

Upcoming Speakers

April 29, 2016
Bruce Lamb, Ph.D.

Executive Director, Stark Neurosciences Research Institute

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

Title: Unraveling the Role of Innate Immunity in Neurodegeneration

Abstract: Neurodegenerative diseases are a major and increasing cause of death and disability in the World. Alzheimer’s disease (AD), frontotemporal dementia (FTD) and chronic traumatic encephalopathy (CTE) amongst many others, are prominent causes of dementia and shortened survival.  Tragically, the progression of these diseases is typically lengthy and there are currently no effective treatments.  Neurodegenerative disease histopathology includes a variety of intracellular and extracellular protein aggregates including extracellular deposits of the beta amyloid peptide (Aβ) in senile plaques in AD and intracellular aggregation of microtubule-associated protein tau (MAPT) and other proteins within neurons in AD, FTD and CTE as well as loss of synapses and specific neuronal populations with age across all neurodegenerative diseases.  In addition, there is dramatic reaction of innate immune cells within the brain.  Genetic findings unambiguously implicate innate immune cells and signaling pathways in neurodegenerative disease pathogenesis.  Most importantly, in late 2012, rare heterozygous coding mutations in TREM2, a gene exclusively expressed by myeloid cells, were identified that substantially increase risk for AD directly implicating innate immunity in neurodegeneration.  Recent studies conducted by the Lamb laboratory and to be presented in this seminar provide novel insights into the expression and cellular localization and role of TREM2 in AD pathogenesis with direct implications for the development and progression of the two hallmark AD pathologies (Aβ and MAPT) and development of a TREM2-focused biomarker for AD.

Co-sponsored with Program in Neuroscience

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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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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: Pending

Abstract: Pending

Co-sponsored with Program in Neuroscience