2015-5-研究生-人类疾病的模式生物学解读.ppt

Flies help clarify cell cycle control mechanisms and lead to identification of new genes which may prevent excessive cell proliferation and cancer * The most common neurodegenerative movement disorder (more than 1% of the population older than 65) Symptoms: Tremor Rigidity Bradykinesia Postural instability Others: cognitive impairment (depression, anxiety, dementia or confusion), swallowing difficulty, speaking difficulty * The goal of the lecture understand drosophila well so that you can understand a paper or seminar, comfortable enough to keep up with the fly literatures on problems and approaches that are relevant for your research. * Drosophila Compound Eye Ommatidium 20+ cells; 8 photoreceptors12 accessory cells 800 Ommatidia Mosaics Used to Tell When and Where a Gene Must be Expressed to Generate Normal Phenotype Ommatidia are facets of fly’s compound eye During development undifferentiated cells are recruited to become photo-receptors (R1-R8) for each facet Final photoreceptor in each group is R7 SCA3果蝇模型 Row1 a 野生型果蝇；b Q78强表达；c Q78弱表达；d Q61强表达 Row2 视网膜厚度 HSP70改善SCA3果蝇的神经退行表型 a 表达Q78 b 共表达Q78与HSP70 c HSP70（显性负效应） d 共表达HSP70（显性负效应）与HSP70 Spermatogenesis and oogenesis Tumor metastasis EyeG4RAS*+GFP EyeG4RAS*+GFP; scrib- PagliariniXu (2003), Science 302, 1227 Parkinson’s Disease Mitochondrial pathology and muscle anddopaminergic neuron degeneration caused byinactivation of Drosophila Pink1 is rescued by Parkin -1 Inhibition of dPink1 by RNAi causes defects of abnormal wing posture, shortened lifespan, and ATP deficit -2 Inhibition of dPink1 results in disrupted IFMs Muscle-specific dPink1 RNAi results in myopathology and agedependent apoptosis in the IFMs -3 Genetic and biochemical interaction between Pink1 and Parkin Mitochondrial dysfunction in Drosophila PINK1mutants is complemented by parkin -1 Characterization of PINK1 mutants -2 Mitochondrial defects in PINK1 mutants -3 Dopaminergic neuronal degeneration in PINK1 mutants In vivo