Madeline Lancaster

Studying human brain evolution in cerebral organoids
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Human intelligence is one of the most exceptional traits in the animal kingdom and is possible because of a number of unique qualities of the human brain. Although many basic mechanisms of brain development have been discerned through animal studies, human-specific qualities remain to be functionally examined. Until recently, this has been due to a lack of an appropriate model system. However, we have recently established an in vitro model of human brain development, termed cerebral organoids.

Cerebral organoids, or mini-brains for short, are 3D tissues generated from human pluripotent stem cells that allow modelling of human brain development in vitro. Through a process of directed differentiation and a supportive 3D microenvironment, neural precursor tissue can spontaneously self-organize to form the stereotypic organization of the early human embryonic brain.

We are using this technology to study the most fundamental differences between human brain development and that of other mammalian species. The successful applicant will be able to take a comparative approach to test for specific molecular and cell biological features in human brain organoids compared with other primates. The student will study the role of candidate genes in this process and how specific perturbations in genetic sequence can lead to important changes in the way our brains develop.


References

Giandomenico SL, Lancaster MA. (2017)
Probing human brain evolution and development in organoids.
Curr Opin Cell Biol. 44:36-43.

Lancaster MA, et al. (2017)
Guided self-organization and cortical plate formation in human brain organoids.
Nat Biotechnol. 35(7):659-666.

Lancaster, M.A. and Knoblich, J.A. (2014)
Generation of cerebral organoids from human pluripotent stem cells.
Nat Protoc. 9(10):2329-40.

Lancaster, M.A. and Knoblich, J.A. (2014)
Organogenesis in a dish: modeling development and disease using organoid technologies.
Science, 345(6194):1247125.

Lancaster, M.A., Renner, M., Martin, C.A., Wenzel, D., Bicknell, L.S., Hurles, M.E., Homfray, T., Penninger, J.M., Jackson, A.P. and Knoblich, J.A. (2013)
Cerebral organoids model human brain development and microcephaly.
Nature, 501(7467):373-9.