Jürgen Knoblich

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Jürgen Knoblich
  
Born1963 (age 57–58)
Memmingen, Germany
NationalityGerman
CitizenshipGermany
Education
  • Biochemistry
  • Molecular Biology
Alma mater
  • University of Tübingen
  • University College London
OccupationMolecular biologist
OrganizationInstitute of Molecular Biotechnology, Vienna
Awards
  • Anniversary Award (FEBS)
  • Young Investigator Award (EMBO)
  • Early Career Award (ELSO)
  • Sir Hans Krebs Medal

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.

Education and Career

Jürgen 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.

Jürgen Knoblich is a member of multiple scientific societies, like the Austrian Academy of Sciences. He holds a position in the Editorial Board of Current Biology,[5] the European Journal of Cell Biology[6]and the Journal of Cell Biology.[7] He has published more than 100 original scientific publications[8] (PubMed, April 2018). Additionally, he regularly teaches at the University of Vienna and the Medical University of Vienna and was appointed Adjunct Professor in 2016.

Research Focus

Jürgen Knoblich’s research[8] is centered around the mechanisms of brain development. His key interests are neuronal stem cells, their asymmetric cell division and processes of growth control. Building on his post-doctoral work, Knoblich and his colleagues characterize 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.[9] 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.[10]

More recently, Jürgen 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.[11] This was achieved using a fruit fly gene bank generated at Institute of Molecular Biotechnology 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.[12] 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,[13] a gene that has been identified by Knoblich and his team.[14] It is currently unknown how many genes with a similar function exist in humans. Knoblich’s research group at Institute of Molecular Biotechnology is trying to identify more of these genes in order to develop less invasive therapies for cancer in the future.

One of the greatest successes of Knoblich to date is the synthesis of an organoid model of early human brain development.[15] This so-called cerebral organoid model was developed by a Madeline A. Lancaster, at that time a postdoctoral fellow in Jürgen Knoblich’s group[16], who later was awarded the “Eppendorf Award for Young European Investigators” for her contribution.[17]. Jürgen Knoblich and his team were 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.[18] Lancaster is now a group leader in the Cell Biology Division of the Medical Research Council Laboratory of Molecular Biology, a part of the Cambridge Biomedical Campus in the United Kingdom.

The model developed by Lancaster and Knoblich is now commonly referred to as “Cerebral organoids”. It faithfully recapitulates the early steps of human brain development during the first trimester and has already been used by many other research groups around the globe.[19][20] Organoid models enable researchers to perform studies directly on human tissues that can be grown from any human individual.[21] 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. In the future, this technology will be advantageous in deciphering other brain defects such as neurodegenerative or neurological disorders and the genes involved in these processes.

Since 2013 Knoblich and his team have further developed their cerebral organoids. Thus, by now 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.[22] This is a promising approach to identify cell defects typical for epilepsy or autism. In 2018, then group used cerebral organoids to model brain cancer in vitro.[23]

Selected Publications

Homem, CC., Steinmann, V., Burkard, TR., Jais, A., Esterbauer, H., Knoblich, JA. (2014). Ecdysone and mediator change energy metabolism to terminate proliferation in Drosophila neural stem cells. Cell. 158(4):874-88

Eroglu, E., Burkard, TR., Jiang, Y., Saini, N., Homem, CC., Reichert, H., Knoblich, JA. (2014). SWI/SNF complex prevents lineage reversion and induces temporal patterning in neural stem cells. Cell. 156(6):1259-73

Lancaster, MA., Renner, M., Martin, CA., Wenzel, D., Bicknell, LS., Hurles, ME., Homfray, T., Penninger, JM., Jackson, AP., Knoblich, JA. (2013). Cerebral organoids model human brain development and microcephaly. Nature. 501(7467):373-9

Awards and Prizes

  • 2001: Anniversary Award of the Federation of European Biochemical Societies (FEBS)
  • 2001: Young Investigator Award of the European Molecular Biology Organization (EMBO)[24][25]
  • 2003: Early Career Award of the European Life Scientist Organization (ELSO)
  • 2009: Wittgenstein-Preis[26][27]
  • 2010: Advanced Research Grant – European Research Council (ERC)[28]
  • 2012: Erwin Schrödinger-Preis of the Austrian Academy of Sciences
  • 2012: Elected member of the Academia Europaea[29]
  • 2013: Elected member of the „mathematisch-naturwissenschaftlichen Klasse“ of the Austrian Academy of Sciences
  • 2015: Sir Hans Krebs Medal of the Federation of European Biochemical Societies (FEBS)

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. "Cell Press: Current Biology". www.cell.com. Retrieved 2020-05-04.
  6. European Journal of Cell Biology Editorial Board.
  7. "Editors and Staff". rupress.org. Retrieved 2020-05-04.
  8. 8.0 8.1 pubmeddev. "knoblich j - PubMed - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-07-16.
  9. 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. PMID 18854163. Retrieved 2020-05-04.
  10. 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. PMID 18854163. Retrieved 2020-05-04.
  11. 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. PMID 19363474. Retrieved 2020-05-04.
  12. 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. doi:10.1038/nature07936. ISSN 1476-4687. PMC 2988197. PMID 19363474.
  13. https://www.uniprot.org/uniprot/Q8MQJ9
  14. I, Reichardt; F, Bonnay; V, Steinmann; I, Loedige; Tr, Burkard; G, Meister; Ja, Knoblich (2018-01-01). "The Tumor Suppressor Brat Controls Neuronal Stem Cell Lineages by Inhibiting Deadpan and Zelda". EMBO reports. PMID 29191977. Retrieved 2020-05-04.
  15. "Dr. Jürgen Knoblich Talks Organoids". www.stemcell.com. Retrieved 2019-11-19.
  16. 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.
  17. "Eppendorf | Nature". www.nature.com. Retrieved 2020-05-04.
  18. "Science's Top 10 Breakthroughs of 2013". Science | AAAS. 2013-12-19. Retrieved 2019-11-19.
  19. 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. PMID 26644564. Retrieved 2020-05-04.
  20. 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. PMID 23995685. Retrieved 2020-05-04.
  21. Hynds, Robert E.; Giangreco, Adam (2013-03-01). "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.
  22. 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.
  23. Bian, Shan; Repic, Marko; Guo, Zhenming; Kavirayani, Anoop; Burkard, Thomas; Bagley, Joshua A.; Krauditsch, Christian; Knoblich, Jürgen A. (August 2018). "Genetically engineered cerebral organoids model brain tumor formation". Nature Methods. 15 (8): 631–639. doi:10.1038/s41592-018-0070-7. ISSN 1548-7105.
  24. "EMBO YIP".
  25. Pathology, Research Institute of Molecular. "EMBO Young Investigator Meeting 2018 at the Vienna BioCenter". The Research Institute of Molecular Pathology. Retrieved 2020-05-04.
  26. "Wittgenstein-Preise 2009 an Jürgen Knoblich und Gerhard Widmer". OTS.at (in Deutsch). Retrieved 2020-05-04.
  27. "Wiener Zeitung". Retrieved 2019-07-16.
  28. "ERC FUNDED PROJECTS". ERC: European Research Council. Retrieved 2019-11-19.
  29. "Academy of Europe: Knoblich Juergen Arthur". www.ae-info.org. Retrieved 2019-11-19.

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