Deciphering the blueprint of the healthy and diseased human brain through the generation of patterned cerebral organoids

The cerebral cortex is the centre of higher-order cognitive functioning in mammal brains. The cortex has undergone an evolutionary expansion and acquired a more sophisticated organization in humans. While the rodent cortex is small and smooth, human and primate cortices are large and convoluted. Nevertheless, key structural features have remained conserved throughout evolution. For instance, the neocortex is subdivided into four primary areas: visual, auditory, somatosensory, and motor. The allocortex is similarly regionalized, and includes the caudomedial hippocampus, which is the seat of learning and memory. How regional patterning occurs during development has been carefully studied in rodent models. Whether similar processes underlie patterning of the human cortex is unknown, but this is an important area of study given the association between neuropsychiatric disorders and altered connectivity between the thalamus and cortex.

This project will use human stem cells to generate self-organizing cerebral organoids (a smaller, simpler version of the organ to be studied) and on-chip cerebral organoid systems to model early brain development and to investigate complex neuropsychiatric diseases, such as autism spectrum disorder. Additionally, the project will provide a strong research environment, as well as capacity building and exchange opportunities, for graduate students and researchers based in India.

The project is led in Canada by the Sunnybrook Research Institute, working in collaboration with the Weizmann Institute of Science in Israel, and the Tata Institute of Fundamental Research in India.

This project was selected for funding through the fourth research competition of the Joint Canada-Israel Health Research Program. This initiative is a partnership between IDRC, the Canadian Institutes of Health Research, the Israel Science Foundation, and the Azrieli Foundation.