Special LMNN SEMINAR // Translating Parkinson’s: Genetic models for target discovery
Event details
| Date | 20.01.2017 |
| Hour | 14:00 › 15:00 |
| Speaker | Richard Wade-Martins, Department of Physiology, Anatomy and Genetics, The University of Oxford, Oxford, UK |
| Location | |
| Category | Conferences - Seminars |
Parkinson's disease (PD) is the second most common neurodegenerative disease and a major unmet clinical need in our ageing population. The focus of the Oxford Parkinson's Disease Centre (OPDC; www.opdc.ox.ac.uk) is to exploit the interdisciplinary research environment within Oxford as a leading centre focused on translational 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, magnetic resonance imaging (MRI), and analysis of protein biomarkers, are working closely with experts in epidemiology and clinical neurology to better understand and ultimately target the causes of PD.
In 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 allow biomarker discovery, MRI and fMRI imaging programs, and genetic analysis by exome resequencing and high-density SNP arrays. In the laboratory we have generated >150 induced pluripotent stem cell (iPSC) lines to derive dopamine neurons from PD patients and controls to allow us to study cellular phenotypes in an accurate, physiologically-relevant model of dopaminergic neurons. We have generated iPS cells from control individuals, from sporadic PD patients and patients carrying mutations in the leucine rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA) genes. Mature dopaminergic neurons with correct morphology express essential protein markers, exhibit 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 expressing mutant or wild-type forms of key genes alpha-synuclein and LRRK2. Rodents transgenic for disease genes show age-dependent motor and non-motor phenotypes and deficits specific to those parts of the brain vulnerable in PD.
This translational program spanning a longitudinal clinical study, human neuronal iPSC models and transgenic rodents encapsulates the key elements required to better understand and ultimately treat a major disease of our time.
In 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 allow biomarker discovery, MRI and fMRI imaging programs, and genetic analysis by exome resequencing and high-density SNP arrays. In the laboratory we have generated >150 induced pluripotent stem cell (iPSC) lines to derive dopamine neurons from PD patients and controls to allow us to study cellular phenotypes in an accurate, physiologically-relevant model of dopaminergic neurons. We have generated iPS cells from control individuals, from sporadic PD patients and patients carrying mutations in the leucine rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA) genes. Mature dopaminergic neurons with correct morphology express essential protein markers, exhibit 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 expressing mutant or wild-type forms of key genes alpha-synuclein and LRRK2. Rodents transgenic for disease genes show age-dependent motor and non-motor phenotypes and deficits specific to those parts of the brain vulnerable in PD.
This translational program spanning a longitudinal clinical study, human neuronal iPSC models and transgenic rodents encapsulates the key elements required to better understand and ultimately treat a major disease of our time.
Practical information
- Informed public
- Free
Organizer
- Laboratory of Molecular and Chemical Biology of Neurodegeneration (LMNN) Host : H. Lashuel