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Ancient DNA, bioengineering and brain "organoids": study of thyroid hormone homeostasis and Alzheimer's Disease markers in NOVA1 gene CRISPR edited stem cells

Grant number: 18/22763-0
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): May 01, 2019
Effective date (End): April 30, 2020
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Rui Monteiro de Barros Maciel
Grantee:Janaína Sena de Souza
Supervisor abroad: Alysson Renato Muotri
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Local de pesquisa : University of California, San Diego (UC San Diego), United States  
Associated to the scholarship:17/07053-3 - Effect of thyroid hormone on the brain of 3xTg-AD mice, model of Alzheimer's Disease, on glucose and cholesterol metabolism, BP.PD


The understanding about the Neanderthal brain was only possible through study of fossils and found bones. This limitation is being overcome due to the marriage of three fields of science: ancient DNA, genome editing (CRISPR) and organoids, which give us the possibility to explore and understand biomolecular mechanisms. The differentiation of stem cells, with gene editing, into "mini brains", that is, organoids that mimic the cortex opens the door for us to explore and understand the functioning of these cells. Even organoids presenting an early stage of development, we can try to answer important questions such as whether there is any difference in the expression of genes related to homeostasis of the thyroid hormone, very important for neuronal development and, if these cells, cells that mimic Neanderthals cells, have the ability to express proteins related to Alzheimer's disease. The aim of this study is to evaluate thyroid hormone homeostasis and Alzheimer's disease markers in edited cells. To do this, we will differentiate hiPSC and ediPSC into organoids and treat and analyze the expression of TH related genes and AD markers through qPCR, immunohistochemistry, ELISA. We believe that this study will contribute with the understanding of the relevance of TH to brain complex development and AD prevalence.