Jay research group: Human organoids for aging research and environmental medicine

Liaison-Group between the IUF and the Institute of Human Genetics of the Heinrich Heine University

Generation of human brain organoids “Brains in a dish” to study brain development. (Gabriel et al., EMBO Journal 2016).

Head of research group:
Univ.-Prof. Jay Gopalakrishnan, PhD tl_files/bilder/mail.gif  

 

Postdocs:
Dr. Anand Ramani

External link:

www.centrosome-cilia-lab.com

Research profile

Environmental hazards such as air pollutants, ionizing radiation and xenobiotics pose major threats to human health. Cellular damages induced by these hazards are complex and difficult to model because of their complexity. Even modeled, most of our current knowledge results from animal models, which may not sufficiently recapitulate the actual cellular damages occurring in humans. To predict health risks and design strategies for prevention and treatments, it is essential to model environmentally induced cellular damages in disease-relevant “human organoids” in 3D. Organoids are 3D in vitro human tissues that mimic tissue counter parts of various organs. These human organoids will not only reduce the usage of animals but may also help to better recapitulate consequences actually occurring in humans. Generating these in vitro human organoids requires a reductionist approach starting from how stem cells organize into complex tissues.

 

We exploited the self-assembling property of iPSC-derived neural progenitor cells (NPCs) and generated 3D human brain organoids (mini brains in dish), which reliably recapitulate many of the complexities of brain tissues. Building on this system, we will conduct a multidisciplinary research program to address the following specific aims: (1) To advance brain organoid culturing technology to generate brain organoids exhibiting expanded cortical layers and higher order brain regions. (2) To model ionizing radiation, methamphetamine and alcohol-induced neurodevelopmental defects. (3) To use brain organoids to model neurodegeneration and relating it to neurodegeneration-like effects caused by environmental pollutants.

 

For these experiments we will use human 3D tissues in combination with latest genomic editing and high resolution imaging technologies.

Cooperations

IUF Internal:
Core Unit Model Development (Head: A. Rossi)
Fritsche research group
Krutmann research group
von Mikecz research group
Schins research group
Ventura research group

Selected publications

Gabriel E, Gopalakrishnan J: Generation of iPSC-derived human brain organoids to model early neurodevelopmental disorders. J Vis Exp 14: 122, 2017. [pubmed]

 

Gabriel E, Ramani A, Karow U, Gottardo M, Natarajan K, Gooi LM, Goranci-Buzhala G, Krut O, Peters F, Nikolic M, Kuivanen S, Korhonen E, Smura T, Vapalahti O, Papantonis A, Schmidt-Chanasit J, Riparbelli M, Callaini G, Krönke M, Utermöhlen O, Gopalakrishnan J: Recent Zika virus isolates induce premature differentiation of neural progenitors in human brain organoids. Cell Stem Cell 20: 1-10, 2017. [pubmed] (open access)

 

Gabriel E, Wason A, Ramani A, Gooi LM, Keller P, Pozniakovsky A, Poser I, Noack F, Telugu NS, Calegari F, Šarić T, Hescheler J, Hyman AA, Gottardo M, Callaini G, Alkuraya FS, Gopalakrishnan J: CPAP promotes timely cilium disassembly to maintain neural progenitor pool. EMBO J. 35(8): 803-819, 2016. (Cover article) [pubmed] (open access)