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Modeling Cockayne Syndrome with Brain Organoids

Grant number: 18/23023-0
Support type:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): February 01, 2019
Effective date (End): January 31, 2020
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Carlos Frederico Martins Menck
Grantee:Lívia Luz Souza Nascimento
Supervisor abroad: Alysson Renato Muotri
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : Sanford Consortium for Regenerative Medicine, United States  
Associated to the scholarship:17/10502-4 - Relevance of oxidative stress in induced pluripotent cells and neural progenitors derived from Cockayne Syndrome patients, BP.DD

Abstract

Cockayne Syndrome (CS) is a rare autosomal disease defined as an association of developmental impairment and premature aging, with a very complex and devastating neurological dysfunction. It is caused by mutations in ERCC8 or ERCC6 genes, which encodes for CSA and CSB proteins, respectively, that are part of the transcription coupled nucleotide excision repair (TC-NER). TC-NER is famously known as an photo-lesion solving pathway, how this is linked to the profound neurological impairment is CS patients remains unknown. This will be a pioneer study using brain organoids to understand CS pathophysiology. The generation of brain organoids from CS patients will allow us to explore, for the first time, characteristics such as 3D architecture, organoid self-organization/formation and maintenance, all of which with potential to recapitulate disease-relevant phenotypes such as microcephaly and cell loss. We believe this project has a great potential to increase our understanding of CS neuropathology and how it is linked to TC-NER using antioxidant therapy.