Alexander F. Schier

Alexander F. Schier (born 1964) is a Professor of Cell Biology and the Director of the Biozentrum University of Basel, Switzerland.[2]

Alexander F. Schier
Born
Switzerland
CitizenshipSwitzerland, USA
Alma materUniversity of Basel (1988)
Known forResearch with zebrafish (Danio rerio)
Embryogenesis
Sleep
AwardsMcKnight Scholar for Neuroscience (1999-2002)
Irma T. Hirschl Scholar (2001-2005)
McKnight Neuroscience of Brain Disorders Award (2006-2008)
Everett Mendelsohn Excellence in Mentoring Award (2014)
NIH MERIT Award (2016)
NIH Pioneer Award (2017)
Election to EMBO (2018)
Science Breakthrough of the Year (2018)[1]
ERC Advanced Grant (2020)
George Streisinger Award of the International Zebrafish Society (2020)
Election to National Academy of Sciences (2020)
Scientific career
FieldsCell Biology
Development
Genetics
Neurobiology
Behavior
InstitutionsBiozentrum of the University of Basel (Switzerland)
Massachusetts General Hospital, Boston (USA)
Skirball Institute, NYU School of Medicine (USA)
Department of Molecular and Cellular Biology, Harvard University (USA)
Doctoral advisorWalter J. Gehring
Other academic advisorsWolfgang Driever

Schier received a B.A. in cell biology in 1988 from the Biozentrum of the University of Basel, Switzerland, followed by a PhD in cell biology in 1992 under Walter J. Gehring, also from the University of Basel, Switzerland. He conducted his postdoctoral research in Wolfgang Driever's lab at the Massachusetts General Hospital and Harvard University in Boston, US. In 1996, Schier was recruited as assistant professor in the Developmental Genetics Program to the Skirball Institute and Department of Cell Biology, NYU School of Medicine.

From 2005 to 2019, he was a professor at the Department of Molecular and Cellular Biology, Harvard University, Faculty of Arts and Sciences. In 2013 he became the Leo Erikson Life Sciences Professor. He chaired the Department of Molecular and Cellular Biology from 2014 to 2017. Since 2017 Schier is a site director of the Allen Discovery Center for Cell Lineage Tracing. In 2018, Schier became the Director of the Biozentrum of the University of Basel as well as Professor for Cell Biology.

Research

Schier is internationally recognized for his pioneering work on vertebrate development using zebrafish (Danio rerio) as a model organism. During his postdoctoral work, Schier and colleagues performed one of the first large-scale forward genetic screens in a vertebrate.[3][4]

In his own lab, Schier has made fundamental contributions to the understanding of the molecular basis of vertebrate embryogenesis, including signaling,[5][6][7][8][9][10][11][12] cell fate determination,[6][7][13][14] cell movement,[11] the maternal-zygotic transition,[15][16] microRNAs,[9][15][17] chromatin[18] and non-coding RNAs.[19] Schier's more recent interest in behavior has established zebrafish as a model for sleep[20][21] and behavioral[22] research, determined neural circuits that underlie sleep[20] identified small molecule sleep regulators[21] and studied the roles of schizophrenia-associated genes REF Thyme Cell 2019.

He has contributed to the development of zebrafish as model system, including positional cloning,[5] germ-line replacement to generate maternal-effect mutants,[23] photobleaching and photo conversion,[10] Brainbow imaging,[14] brain activity atlas,[24] small molecule profiling,[21] transcriptomics[19][25] and epigenomics,[18] gene annotation,[11][19][26][27] CRISPR/Cas9 genome editing,[28][29][30] lineage tracing by genomic barcode editing[31] and reconstruction of developmental trajectories by single-cell RNA-sequencing.[32]

Mentoring

Schier is also well known for having an unusually high rate of placing trainees in academic positions. Previous mentees have gone on to PI positions at Yale, Princeton, Caltech, UCLA, University of Toronto, U Mass Amherst, NYU School of Medicine, University College London, MPI Dresden, University of Tokyo, UCSD, University of Calgary, MPI Tuebingen, IMP Vienna, University of Utah, Cambridge University and NIH. Key to his mentoring philosophy are five questions he has developed to sharpen the thoughts of his mentees (see also [33]):

  • Do you work on an important problem?
  • Do you work with sustained concentration?
  • Do you have a sense of urgency?
  • Are you able to troubleshoot?
  • Do you have the killer instinct to do the key experiments that will result in a coherent, conclusive and publishable study?

Awards
  • 1999-2002 McKnight Scholar for Neuroscience
  • 2001-2005 Irma T. Hirschl Scholar
  • 2002-2005 Established Investigator of the American Heart Association
  • 2006 Harland Winfield Mossman Developmental Biologists Award of the American Asc. of Anatomists
  • 2006-2008 McKnight Neuroscience of Brain Disorders Award
  • 2014 Everett Mendelsohn Excellence in Mentoring Award from Harvard's Graduate Student Council
  • 2016 NIH MERIT Award
  • 2016 Bjorkman-Strominger-Wiley Prize for Collaboration (with Florian Engert)
  • 2017 NIH Pioneer Award
  • 2018 Election to EMBO
  • 2018 Science “Breakthrough of the Year 2018”
  • 2020 ERC Advanced Grant
  • 2020 George Streisinger Award of the International Zebrafish Society
  • 2020 Election to National Academy of Sciences

References
  1. Science Breakthrough of the Year (2018) harvard.edu Retrieved 2019-12-12
  2. Alex Schier Appointed New Director of the Biozentrum unibas.ch Retrieved 2019-12-12
  3. Schier, A.F., Neuhauss, S. C. F., Harvey, M., Malicki, J., Solnica-Krezel, L., Stainier, D. Y. R., Zwartkruis, F., Abdelilah, S., Stemple, D. L., Rangini, Z., Yang, H. and Driever, W. (1996). Mutations affecting the development of the embryonic zebrafish brain. Development 123, 165 - 178
  4. Schier, A. F., Neuhauss, S. C., Helde, K. A., Talbot, W. S., & Driever, W. (1997). The one-eyed pinhead gene functions in mesoderm and endoderm formation in zebrafish and interacts with no tail. Development, 124(2), 327–342.
  5. Zhang, J., Talbot, W.S., and Schier, A.F. (1998). Positional cloning identifies zebrafish one-eyed pinhead as a permissive EGF-related ligand required during gastrulation. Cell 92, 241-251.
  6. Gritsman, K., Zhang, J., Cheng, S., Heckscher, E., Talbot, W.S., and Schier, A.F. (1999). The EGF-CFC protein one-eyed pinhead is essential for nodal signaling. Cell 97, 121-132.
  7. Chen, Y. and Schier, A.F. (2001). The zebrafish nodal signal squint functions as a morphogen. Nature 411, 607-610.
  8. Ciruna, B., Jenny, A., Lee, D., Mlodzik, M. and Schier, A.F. (2006). Planar cell polarity signalling couples cell division and morphogenesis during neurulation. Nature 439, 220-224.
  9. Choi, W.-Y., Giraldez, A.J. and Schier, A.F. (2007). Target Protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430. Science 318, 271-274.
  10. Mueller, P. Rogers, K.W., Jordan, B.M.; Lee, J.S., Robson, D., Ramanathan, S., and Schier A.F. (2012). Differential diffusivity of Nodal and Lefty underlies a reaction-diffusion patterning system. Science 336, 721-4.
  11. Pauli, A., Norris, M.L., Valen, E., Chew, G.-L., Gagnon, J.A., Zimmerman, S., Mitchell, A., Ma, J., Dubrulle, J., Reyon, D., Tsai, S.Q., Joung, J.K., Saghatelian, A., and Schier, A.F. (2014). Toddler: an embryonic signal that promotes cell movement via Apelin receptors. Science 343, 1248636
  12. Dubrulle, J., Jordan, B.M., Akhmetova, L., Farrell, J.A., Kim, S.-H., Solnica-Krezel, L. and Schier, A.F. (2015) Response to Nodal morphogen gradient is shaped by the kinetics of target gene induction. eLIFE doi:10.7554/eLife.05042.
  13. Huang, P., Xiong, F., Megason, S. G., & Schier, A. F. (2012). Attenuation of Notch and Hedgehog signaling is required for fate specification in the spinal cord. PLoS Genetics, 8(6), e1002762. doi:10.1371/journal.pgen.1002762
  14. Pan YA, Freundlich T, Weissman TA, Schoppik D, Wang XC, Zimmerman S, Ciruna B, Sanes JR, Lichtman JW, Schier AF (2013). Zebrabow: multispectral cell labeling for cell tracing and lineage analysis in zebrafish. Development, 140(13), 2835–2846. doi:10.1242/dev.094631
  15. Giraldez, A.J., Mishima, Y., Rihel, J., Grocock, R.J., Van Dongen, S., Inoue, K., Enright, A.J. and Schier, A.F. (2006). Zebrafish miR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312, 75-79.
  16. Schier AF (2007). "The Maternal-Zygotic Transition: Death and Birth of RNAs". Science 316 (5823): 406–7.
  17. Giraldez, A.J., Cinalli, R. Glasner, M.E., Enright, A., Thomson, J.M., Baskerville, S., Hammond, S.M., Bartel, D. and Schier, A.F. (2005). MicroRNAs regulate brain morphogenesis in zebrafish. Science 308, 833-838.
  18. Vastenhouw, N.L., Zhang, Y., Woods, I.G., Imam, F., Regev, A., Liu, X.S., Rinn, J., and Schier, A.F. (2010). Chromatin signature of embryonic pluripotency is established during genome activation. Nature 464, 922-6. PMC 2874748.
  19. Pauli, A., Valen, E., Lin, M.F., Garber, M., Vastenhouw, N.L., Levin, J.Z., Fan, L., Sandelin, A., Rinn, J.L., Regev, A., and Schier, A.F. (2012). Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis. Genome Research 22, 577-91. Epub 2011 Nov 22.
  20. Prober, D. A., Rihel, J., Onah, A. A., Sung, R.-J., & Schier, A. F. (2006). Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish. Journal of Neuroscience, 26(51), 13400–13410. doi:10.1523/JNEUROSCI.4332-06.2006
  21. Rihel, J., Prober, D., Arvanites, A., Lam, K., Zimmerman, S., Jang, S., Haggarty, S.J., Kokel, D., Rubin, L.L., Peterson, R.T. and Schier, A.F. (2010). Behavioral profiling links drugs to biological targets and the regulation of rest/wake states. Science 15, 348-51. PMC 2830481
  22. Woods IG, Schoppik D, Shi VJ, Zimmerman S, Coleman HA, Greenwood J, Soucy ER, Schier AF (2014). Neuropeptidergic signaling partitions arousal behaviors in zebrafish. Journal of Neuroscience, 34(9), 3142–3160. doi:10.1523/JNEUROSCI.3529-13.2014
  23. Ciruna, B., Weidinger, G., Knaut, H., Thisse, B., Thisse, C., Raz, E., & Schier, A. F. (2002). Production of maternal-zygotic mutant zebrafish by germ-line replacement. Proceedings of the National Academy of Sciences of the United States of America, 99(23), 14919–14924. doi:10.1073/pnas.222459999
  24. Randlett, O., Wee, C., Naumann, E.A., Nnaemeka, O., Schoppik, D., Fitzgerald, J.E., Portugues, R., Lacoste, A., Riegler, C., Engert, F.*, and Schier, A.F. * (2015). Whole-brain activity mapping onto a zebrafish brain atlas. Nature Methods 12, 1039-46.
  25. Satija, R., Farrell, J., Gennert, D., Schier, A.F., and Regev, A. (2015). Seurat: Spatial reconstruction of single-cell gene expression. Nature Biotechnology 33, 495-502.
  26. Chew, G.-L., Pauli, A., Rinn, J. L., Regev, A., Schier, A. F., & Valen, E. (2013). Ribosome profiling reveals resemblance between long non-coding RNAs and 5' leaders of coding RNAs. Development, 140(13), 2828–2834. doi:10.1242/dev.098343
  27. Chew, G.-L., Pauli, A, and Schier, A.F. (2016). Conservation of uORF repressiveness and sequence features in mouse, human and zebrafish. Nature Communications 7, 11663.
  28. Gagnon JA, Valen E, Thyme SB, Huang P, Ahkmetova L, Pauli A, Montague TG, Zimmerman S, Richter C, Schier AF (2014). Efficient Mutagenesis by Cas9 Protein-Mediated Oligonucleotide Insertion and Large-Scale Assessment of Single-Guide RNAs. PLoS ONE, 9(5), e98186. doi:10.1371/journal.pone.0098186
  29. Thyme, S. and Schier, A.F. (2016). Polq-Mediated End Joining Is Essential for Surviving DNA Double-Strand Breaks during Early Zebrafish Development. Cell Reports 15, 1611-1613.
  30. Thyme, S.B., Akhmetova, L., Montague, T.G., Valen, E. and Schier, A.F. (2016). Internal guide RNA interactions interfere with Cas9-mediated cleavage. Nature Communications 7, 11750.
  31. McKenna, A., Findlay, G.F., Gagnon, J.A., Horwitz, M.S., Schier, A.F., and Shendure, J. (2016). Whole organism lineage tracing by combinatorial and cumulative genome editing. Science aaf7907.
  32. Farrell, Jeffrey A; Wang, Yiqun; Riesenfeld, Samantha J; Shekhar, Karthik; Regev, Aviv; Schier, Alexander F (2018). Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis. Science, 360 (6392), 6.
  33. http://www.cell.com/current-biology/pdf/S0960-9822(04)00437-3.pdf
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