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SUMMARY:Special LMNN SEMINAR // Translating Parkinson’s: Genetic models 
 for target discovery
DTSTART:20170120T140000
DTEND:20170120T150000
DTSTAMP:20260506T221153Z
UID:ce7bf0d97a275b770727c7becff791bd1a580cb919defceb1b634203
CATEGORIES:Conferences - Seminars
DESCRIPTION:Richard Wade-Martins\, Department of Physiology\, Anatomy and 
 Genetics\, The University of Oxford\, Oxford\, UK\nParkinson's disease (PD
 ) is the second most common neurodegenerative disease and a major unmet cl
 inical need in our ageing population. The focus of the Oxford Parkinson's 
 Disease Centre (OPDC\; www.opdc.ox.ac.uk) is to exploit the interdisciplin
 ary research environment within Oxford as a leading centre focused on tran
 slational research understanding the earliest pathological pathways in PD.
  Groups with strengths in genetics and genomics\, transgenic rodent models
 \, in vivo neuroanatomy and neuropharmacology of the basal ganglia\, magne
 tic resonance imaging (MRI)\, and analysis of protein biomarkers\, are wor
 king closely with experts in epidemiology and clinical neurology to better
  understand and ultimately target the causes of PD.\n \nIn the clinic we 
 have collected 1000 PD patients\, plus age-matched controls and "at-risk" 
 individuals for our longitudinal study. The cohort is being studied to all
 ow biomarker discovery\, MRI and fMRI imaging programs\, and genetic analy
 sis by exome resequencing and high-density SNP arrays. In the laboratory w
 e have generated >150 induced pluripotent stem cell (iPSC) lines to derive
  dopamine neurons from PD patients and controls to allow us to study cellu
 lar phenotypes in an accurate\, physiologically-relevant model of dopamine
 rgic neurons. We have generated iPS cells from control individuals\, from 
 sporadic PD patients and patients carrying mutations in the leucine rich r
 epeat kinase 2 (LRRK2) and glucocerebrosidase (GBA) genes. Mature dopamine
 rgic neurons with correct morphology express essential protein markers\, e
 xhibit key neurophysiological features and reveal neurobiological deficits
  in PD lines. To better understand and model the sequence of events which 
 occurs in vivo in PD we have created BAC transgenic mice and rats expressi
 ng mutant or wild-type forms of key genes alpha-synuclein and LRRK2. Roden
 ts transgenic for disease genes show age-dependent motor and non-motor phe
 notypes and deficits specific to those parts of the brain vulnerable in PD
 .\n \nThis translational program spanning a longitudinal clinical study\,
  human neuronal iPSC models and transgenic rodents encapsulates the key el
 ements required to better understand and ultimately treat a major disease 
 of our time.\n 
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717
STATUS:CONFIRMED
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