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The laboratory for centrosome and cytoskeleton biology

Institute of Human Genetics, Heinrich-Heine-Universität Düsseldorf, Germany.

Our research

"I have not failed. I've just found 10,000 ways that won't 'work" Thomas A. Edison

We are a group of scientists interested in understanding the basic principles of centrosomes and cilia biogenesis. We use Drosophila (fruit fly) as a model organism.

We then apply our ideas in iPSC-derived human brain organoids to understand how centrosomes and cilia regulate brain development.

OUR RESEARCH

Centrosomes are the major microtubule organizing centers of animal cells (MTOC) essential for accurate cell division, maintaining genome integrity and cilia formation. At their core, centrosomes are composed of a pair of centrioles surrounded by a protein network of Peri-Centriolar Material (PCM)

The number of centrosomes within a cell is strictly regulated, and their duplication is limited to once per cell cycle. Likewise, assembly and disassembly of the primary cilium is also tightly correlated with cell cycle progression where cilium assembly is associated with quiescence (G0) and cilium disassembly with cell cycle re-entry at the onset of mitosis (G2 to M). Therefore, regulated centrosome and cilium biogenesis are critical for normal animal development.

Mutations in centrosomal genes underlie neurodevelopmental disorders such as primary microcephaly. On the other hand, increased centrosome numbers can drive chromosomal instability and cancer cell invasion making supernumerary centrosomes, a hallmark of cancer.

The overall goal is to understand fundamental mechanisms of centrosome / cilium biogenesis and dissect how are they deregulated in human developmental disorders and cancer.  In the long term, we envision to translate our knowledge to develop targeted interventions to control cancer cell proliferation.

SPECIFIC QUESTIONS

-Biochemistry of centrosomal protein interactions during centrosome biogenesis

-Cilia checkpoint in cell cycle progression

-Centrosomes and cilia in neural stem cell maintenance

-Targeting centrosomal mechanisms using chemical probes for human cancers

-Developing human brain organoid culturing technologies to model brain development, retinal development, and tumorigenesis.

-Human brain organoids to model genetically caused microcephaly and microcephaly caused by neurotropic viral infections.

IMPACT

Our research will uncover previously unknown mechanisms of neural stem cell maintenance in human brain development and tumorigenesis. The application of basic biology and brain organoid systems will model human brain disorders and allow us to apply drug discovery programs for human diseases.

 

 

 

 

Our concept

"Identifying the tunable biochemical mechanisms of centrosomes and cilia biogenesis and target them in engineered 3D human tissues for clinical application"