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NOD 2007-1 • Capitalizing on what drives biomedical science and scientists? – Curiosity – Competition (fame and fortune?) – Desire to solve a health problem or a disease • The approaches – Fundamental or basic science – Disease-oriented research – Translational research • Sticking points – Interdisciplinary training – Communication between basic and clinical scientists Philosophy and Goals for the course-2 • To initiate thinking re: disease mechanisms • “ready observer” concept • Consider mechanisms across disease boundaries • Exposure to a few diseases and clinical material What it is and is not-3 • It is – An overview – A sampler – A way of thinking about disease mechanisms • It is not – – – – Spoon-fed learning Comprehensive An aid for you in writing the first paragraph of a grant A promotional spot for translational research Logistics-4 • Course meeting times • “Overviews”, ToolBoxes” and “Clinical Demonstrations” • Visiting lecturers/lunches • Reading assignments and Website materials • Extras – Movies – Clinical rounds the last week • Assessments and Participation – Open format – I want to know if you will not be present – Special issues around presentations/clinical demonstrations The “By-Disease” Approach • Common for textbooks and courses on this topic • Examples – Gilman textbook - 97 chapters – NINDS website - 600 listings not counting NIMH, NIDA etc • Useful for clinical diagnosis and as reference material • Less useful for discovery science as virtually all mechanisms and themes cross disease boundaries The theme approach to Neurobiology of Disease-6 1. Cell injury energy metabolism mitochondria oxidative injury free radicals and metals 2. Cell death programmed cell death apoptosis necrosis cell cycle proteins, growth control signaling cascades 3. Protein folding and misfolding chaperones aggregation ubiquitin/proteosome system The theme approach to Neurobiology of Disease-7 4. Cell signaling and cell-cell interactions kinases, phosphatases cell adhesion neuronal-glial interactions trophic interactions 5. Development and synaptogenesis neurogenesis, cell fate determination migration and lamination synaptogenesis and synaptic targeting synaptic dysfunction circuitry abnormalities 6. Neuroplasticity adaptive and maladaptive membrane excitability reward mechanisms addiction HPA-stress axis The theme approach to Neurobiology of Disease-8 7. Regeneration and repair mechanisms normal and maladaptive autoimmune – T,B cell immunity inflammatory – cytokines, microglia 8. Single genes and disease single gene disorders, e.g.channelopathies gene discovery strategies 9. Multigenic disease genetic susceptibility transcriptional regulation gene discovery strategies animal models and humans 10. Toxins and environmental influences movement disorders neurodegeneration mechanisms of neurotoxins epigenetics This year’s themes-9 • Intro week – Thematic approach, Bench-Bedside, Clinical Trials • Genes and Disease – This year’s clinical example: Epilepsy • Maladaptive plasticity – This year’s clinical example: Addiction • Regeneration and Repair – This year’s clinical example: MS • Neurodegeneration – This year’s clinical example: Parkinson’s Disease • Student Presentations/Clinical Rounds