Tuesday, 21 March 2017 at 11:00 | Large Operon, EMBL Heidelberg
Jürgen Knoblich | Institute of Molecular Biotechnology, Vienna (A)
Hosts: Anne Ephrussi, Developmental Biology Unit; Jan Ellenberg & Pierre Neveu, Cell Biology and Biophysics Unit; Bernhard Hampoelz, Structural and Computational Biology Unit
Modelling human brain development and disease in stem cell derived 3D organoid culture
The human brain is highly unique in size and complexity. While many of its characteristics have been successfully studied in model organisms, recent experiments have emphasised unique features that can not easily be modeled in animals. We have therefore developed a 3D organoid culture system derived from human pluripotent stem cells that recapitulates many aspects of human brain development. These cerebral organoids are capable of generating several brain regions including a well-organised cerebral cortex. Furthermore, human cerebral organoids display stem cell properties and progenitor zone organisation that show characteristics specific to humans. Finally, we use both RNAi and patient specific iPS cells to model microcephaly, a human neurodevelopmental disorder that has been difficult to recapitulate in mice. This approach reveals premature neuronal differentiation with loss of the microcephaly protein CDK5RAP2, a defect that could explain the disease phenotype. Our data demonstrate an in vitro approach that recapitulates development of even this most complex organ, which can be used to gain insights into disease mechanisms.
Jürgen Knoblich is a senior scientist and deputy director at IMBA. He obtained his PhD from the Max Planck Institute in Tübingen. After a postdoctoral period in the laboratory of Yuh Nung Jan at UCSF, San Francisco, he joined the IMP in 1997 as a junior group-leader. In 2004, he moved to IMBA where he is now senior scientist and deputy director.
His laboratory is interested in the biology of neural stem cells. In the fruitfly, they have identified the molecular mechanism that allows neural stem cells to segregate protein determinants into only one daughter cell during mitosis and to divide asymmetrically. They have demonstrated that defects in this mechanism lead to brain tumor formation. More recently, they have extended their interest to analysing mammalian neural progenitors and their contribution to brain development. To analyse those processes in humans, they have established a 3D culture system that recapitulates the early steps of human brain development in cell culture allowing brain pathologies and human specific developmental events to be studied in unprecedented detail.
Jürgen Knoblich has received several awards such as the Wittgenstein prize, the Schroedinger award and the FEBS anniversary award. He is a member of the European Molecular Biology Organisation (EMBO) and the Austrian Academy of Sciences and acts on the EMBO council and the editorial boards of Current Biology and the European Journal of Cell Biology.