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SUMMARY:Elucidating molecular mechanisms of neurodegeneration with CRISPR-
 based functional genomics - Martin Kampmann\, Department of Biochemistry a
 nd Biophysics Institute for Neurodegenerative Diseases University of Calif
 ornia\, San Francisco\, USA
DTSTART:20200303T140000Z
DTEND:20200303T150000Z
UID:TALK140218@talks.cam.ac.uk
CONTACT:Ritwick Sawarkar
DESCRIPTION:Human genes associated with brain-related diseases are being d
 iscovered at an accelerating pace. A major challenge is the identification
  of the mechanisms through which these genes act\, and of potential therap
 eutic strategies. To elucidate such mechanisms in relevant human cell type
 s\, we established a CRISPR-based platform for genetic screening in human 
 iPSC-derived neurons\, astrocytes and microglia. In an application relevan
 t for Alzheimer’s Disease and other neurodegenerative diseases\, we are 
 using this platform to understand cellular mechanisms controlling the aggr
 egation\, spreading\, and toxicity of the protein tau. Tau aggregates are 
 a hallmark of Alzheimer’s Disease and tauopathies. Mutations in tau are 
 linked to familial neurodegenerative diseases. However\, we still lack con
 sensus on the molecular mechanisms by which tau contributes to neurodegene
 ration. Intriguingly\, different types of neurons show selective vulnerabi
 lity to tau aggregation\, suggesting that cellular pathways play a key rol
 e in controlling aggregation and resulting toxicity. A systematic understa
 nding of these pathways would enable a mechanistic understanding of the di
 sease processes and point to potential therapeutic targets. Our screens ha
 ve identified roles for specific cellular pathways\, including specific ch
 aperones and co-chaperones\, autophagy\, mitochondrial function\, and some
  factors with mostly uncharacterized function. We are using biochemistry a
 nd cell biology to clarify the mechanisms by which these factors control t
 au aggregation and toxicity\, and to evaluate their potential as therapeut
 ic targets.
LOCATION:MRC Laboratory Of Molecular Biology (LMB)
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