Modeling Cockayne Syndrome with brain organoids

• Grant number: 18/23023-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: February 01, 2019
• End date: 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: Alysson Renato Muotri
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: 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. (AU)