Jürgen Knoblich

Jürgen Knoblich (born 1963 in Memmingen, Germany)[1] is a German molecular biologist. Since 2018, he is Scientific Director of the Institute of Molecular Biotechnology[2] (IMBA) of the Austrian Academy of Sciences in Vienna.   

Jürgen Knoblich. ©IMBA/Sandra Schartel

Education and career

Knoblich[3] studied Biochemistry at the University of Tübingen and Molecular Biology at University College London. In 1989 he transferred to the Max Planck Institute for Developmental Biology in Tübingen, where he completed his doctoral thesis in 1994 on the role of Cyclin proteins in controlling cell cycle progression during development. In 1994 he became a postdoctoral researcher at the University of California, San Francisco, where he worked with Dr. Yuh Nung Jan until 1997. Upon his return to Europe he joined the Institute of Molecular Pathology (IMP) in Vienna, Austria as a group leader. In 2004, he moved to the newly founded Institute of Molecular Biotechnology (IMBA) in Vienna, where he was appointed deputy director in 2005 and became scientific director in 2018.[4] Both the IMP and the IMBA are members of the Vienna Biocenter.

Research focus
Cross section of a complete cerebral organoid with different brain regions. Cells are shown in blue, neural stem cells in red and neurons in green.

Knoblich’s research[5] is known for the development [6] of an organoid model of early human brain development,[7][8] together with his postdoctoral fellow Madeline A. Lancaster. His team was the first to demonstrate that organoids derived from human pluripotent stem cells (iPS cells) can be used to model human disease, a breakthrough that was ranked within the top 10 scientific discoveries in 2013 by Science magazine.[9]

This model is now commonly referred to as “Cerebral organoids”. It recapitulates the early steps of human brain development during the first trimester and has been used by many other research groups.[10][11] Organoid models enable researches to perform studies directly on human tissues that can be grown from any human individual.[12] They allow scientists to efficiently transfer research findings from fruit flies and animal models to human tissues and thus to investigate heritable genetic brain diseases on human tissue.

Since 2013 his team have further developed their cerebral organoids. It is possible to generate models that reconstruct the formation of a layered human cortex with a distinct ventricular zone and cortical plate, in which the migration of neurons and neuronal activities can be investigated. In 2017, they showed that by fusing two separately patterned organoids it is possible to study interactions between distinct brain areas.[13]

Previously, his research had also centered around the mechanisms of brain development. His were neuronal stem cells, their asymmetrical cell division and processes of growth control. Building on his post-doctoral work, Knoblich and his colleagues characterized a complete mechanism for asymmetrical stem cell division in neural stem cells of the fruitfly Drosophila. Their results were published in a series of seminal papers, including a report in Cell in 2008.[14] Until then, it was unknown how stem cells can separate into a self-renewing daughter cell and a specialized differentiating cell at the same time. Asymmetric cell division is based on a reaction cascade in which a cascade of molecular switches are activated or inactivated. Proteins in this cascade are either turned “on” or “off” depending on their phosphorylation state, starting with a kinase that transfers the first phosphate residue, named aurora kinase A. Aurora kinase A is often over-expressed in tumor cells, alongside other molecules that also play a role in the process of asymmetric cell division. Since stem cell mitosis is a highly conserved process, results found in fruit flies can be transferred to humans and thereby help to gain insights into general tumor neogenesis[15]

Additionally, Knoblich and his group were the first to carry out a genome-wide in vivo RNAi screen to demonstrate for the first time, that it is possible to simultaneously analyze gene functions across the whole genome of an organism in a tissue specific manner.[16] This was achieved using a fruit fly gene bank generated at IMBA by Barry Dickson, in which every single one of the approximately 13,000 fruit fly genes can be inactivated in any cell independently. These findings have been published in Nature in 2009.[17] With this method, Knoblich could further elucidate brain tumor development in fruit flies. Recent findings suggest that tumors can be based on stem cells, that keep their unique stem cell characteristics and thus uncontrollably divide, without ever differentiating into specific somatic cell types. This lack of differentiation is caused by Brat, a gene that has been identified by Knoblich and his team.[18] It is currently unknown how many genes with a similar function exist in humans. Knoblich’s research group at IMBA is trying to identify more of these genes in order to develop less invasive therapies for cancer in the future.

Selected publications

Honors

References
  1. Jürgen, Knoblich. "CV Knoblich" (PDF). IMBA.
  2. "Jürgen Knoblich - Team". IMBA - Institute of Molecular Biotechnology.
  3. "Juergen A Knoblich | PhD | IMBA Institute Of Molecular Biotechnology, Vienna | ". ResearchGate. Retrieved 2019-07-16.
  4. "IMBA". www.ccc.ac.at. Retrieved 2020-05-04.
  5. pubmeddev. "knoblich j - PubMed - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-07-16.
  6. "Eppendorf | Nature". www.nature.com. Retrieved 2020-05-04.
  7. "Dr. Jürgen Knoblich Talks Organoids". www.stemcell.com. Retrieved 2019-11-19.
  8. Lancaster, Madeline A.; Knoblich, Juergen A. (October 2014). "Generation of cerebral organoids from human pluripotent stem cells". Nature Protocols. 9 (10): 2329–2340. doi:10.1038/nprot.2014.158. ISSN 1750-2799. PMC 4160653. PMID 25188634.
  9. "Science's Top 10 Breakthroughs of 2013". Science | AAAS. 2013-12-19. Retrieved 2019-11-19.
  10. Jg, Camp; F, Badsha; M, Florio; S, Kanton; T, Gerber; M, Wilsch-Bräuninger; E, Lewitus; A, Sykes; W, Hevers (2015-12-22). "Human Cerebral Organoids Recapitulate Gene Expression Programs of Fetal Neocortex Development". Proceedings of the National Academy of Sciences of the United States of America. 112 (51): 15672–7. Bibcode:2015PNAS..11215672G. doi:10.1073/pnas.1520760112. PMC 4697386. PMID 26644564. Retrieved 2020-05-04.
  11. Ma, Lancaster; M, Renner; Ca, Martin; D, Wenzel; Ls, Bicknell; Me, Hurles; T, Homfray; Jm, Penninger; Ap, Jackson (2013-09-19). "Cerebral Organoids Model Human Brain Development and Microcephaly". Nature. 501 (7467): 373–9. Bibcode:2013Natur.501..373L. doi:10.1038/nature12517. PMC 3817409. PMID 23995685. Retrieved 2020-05-04.
  12. Hynds, Robert E.; Giangreco, Adam (March 2013). "The relevance of human stem cell-derived organoid models for epithelial translational medicine". Stem Cells (Dayton, Ohio). 31 (3): 417–422. doi:10.1002/stem.1290. ISSN 1066-5099. PMC 4171682. PMID 23203919.
  13. Bagley, Joshua A.; Reumann, Daniel; Bian, Shan; Lévi-Strauss, Julie; Knoblich, Juergen A. (July 2017). "Fused cerebral organoids model interactions between brain regions". Nature Methods. 14 (7): 743–751. doi:10.1038/nmeth.4304. ISSN 1548-7105. PMC 5540177. PMID 28504681.
  14. F, Wirtz-Peitz; T, Nishimura; Ja, Knoblich (2008-10-03). "Linking Cell Cycle to Asymmetric Division: Aurora-A Phosphorylates the Par Complex to Regulate Numb Localization". Cell. 135 (1): 161–73. doi:10.1016/j.cell.2008.07.049. PMC 2989779. PMID 18854163. Retrieved 2020-05-04.
  15. F, Wirtz-Peitz; T, Nishimura; Ja, Knoblich (2008-10-03). "Linking Cell Cycle to Asymmetric Division: Aurora-A Phosphorylates the Par Complex to Regulate Numb Localization". Cell. 135 (1): 161–73. doi:10.1016/j.cell.2008.07.049. PMC 2989779. PMID 18854163. Retrieved 2020-05-04.
  16. Jl, Mummery-Widmer; M, Yamazaki; T, Stoeger; M, Novatchkova; S, Bhalerao; D, Chen; G, Dietzl; Bj, Dickson; Ja, Knoblich (2009-04-23). "Genome-wide Analysis of Notch Signalling in Drosophila by Transgenic RNAi". Nature. 458 (7241): 987–92. Bibcode:2009Natur.458..987M. doi:10.1038/nature07936. PMC 2988197. PMID 19363474.
  17. Mummery-Widmer, Jennifer L.; Yamazaki, Masakazu; Stoeger, Thomas; Novatchkova, Maria; Bhalerao, Sheetal; Chen, Doris; Dietzl, Georg; Dickson, Barry J.; Knoblich, Juergen A. (2009-04-23). "Genome-wide analysis of Notch signalling in Drosophila by transgenic RNAi". Nature. 458 (7241): 987–992. Bibcode:2009Natur.458..987M. doi:10.1038/nature07936. ISSN 1476-4687. PMC 2988197. PMID 19363474.
  18. I, Reichardt; F, Bonnay; V, Steinmann; I, Loedige; Tr, Burkard; G, Meister; Ja, Knoblich (January 2018). "The Tumor Suppressor Brat Controls Neuronal Stem Cell Lineages by Inhibiting Deadpan and Zelda". EMBO Reports. 19 (1): 102–117. doi:10.15252/embr.201744188. PMC 5757284. PMID 29191977.
  19. "EMBO YIP".
  20. Pathology, Research Institute of Molecular. "EMBO Young Investigator Meeting 2018 at the Vienna BioCenter". The Research Institute of Molecular Pathology. Retrieved 2020-05-04.
  21. "Wittgenstein-Preise 2009 an Jürgen Knoblich und Gerhard Widmer". OTS.at (in German). Retrieved 2020-05-04.
  22. "Wiener Zeitung". Retrieved 2019-07-16.
  23. "ERC FUNDED PROJECTS". ERC: European Research Council. Retrieved 2019-11-19.
  24. "Academy of Europe: Knoblich Juergen Arthur". www.ae-info.org. Retrieved 2019-11-19.
  25. "Cerebral organoids: an innovative treatment for neurological disorders". ERC: European Research Council. 2018-07-25. Retrieved 2020-06-01.
  26. "ERC FUNDED PROJECTS". ERC: European Research Council. Retrieved 2020-07-02.
  27. "Rinunce e nomine". press.vatican.va. Retrieved 2020-10-09.
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