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Understanding the role of CHD7 in brain development: CHARGE syndrome and ASD

Project description

Mutations in the gene coding chromodomain-helicase-DNA-binding protein 7 (CHD7), an ATP-dependent chromatin remodeller, are the primary cause of CHARGE syndrome and have been associated to CHARGE syndrome. However, the neuropathological mechanisms underlying brain abnormalities in these disorders, upon CHD7 mutations, remain unknown. It is well-known that CHD7 regulates gene transcription. I therefore hypothesize that CHD7 regulates genes that are crucial for proper neural network development, function and maintenance in the brain. Using the zebrafish – a powerful tool for studying such a neurodevelopmental disorder, we have created a zebrafish chd7 mutant using CRISPR / Case 9. Using this model and transgenic fish that express fluorescent protein in specific neuron types, I plan to first characterize the defects in the mutant brain. Further, an RNA-seq experiment will identify the genes that are dysregulated upon chd7 mutation, and guide us to identifying pathways that could be involved. This will help in understanding the mechanisms of the CHARGE syndrome with a particular emphasis on the brain defects. Lastly, we also propose to perform a drug screen of FDA-approved compounds in their abilities to restore / ameliorate symptoms of CHARGE syndrome in a simple genetic model. Our findings have the potential to be translated into the clinic for human trials.

Research team

Name: Priyanka Jamadagni, M.Sc
Supervisor: Kessen Patten (INRS)
Laureate: Doctoral scholarship 2018 and 2019

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