Alexander F. Schier

Alexander F. Schier
Born Switzerland
Residence USA
Citizenship Switzerland, USA
Alma mater University of Basel (1988)
Known for Research with zebrafish (Danio rerio)
Embryogenesis
Sleep
Awards McKnight 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)
Scientific career
Fields Cell Biology
Development
Genetics
Neurobiology
Behavior
Institutions Biozentrum at 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 advisor Walter J. Gehring
Other academic advisors Wolfgang Driever

Alexander F. Schier (born 1964) is the Leo Erikson Life Sciences Professor in the Department of Molecular and Cellular Biology at Harvard University. He is a member of the Center for Brain Science, a member of the Center for Systems Biology, a principal member of the Harvard Stem Cell Institute, and an associate member of the Broad Institute of MIT and Harvard.

Schier received a B.A. in Cell Biology in 1988 from the Biozentrum at 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, USA. 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. Since 2005, he has been Professor at the Department of Molecular and Cellular Biology, Harvard University, Faculty of Arts and Sciences. He chaired the department from 2014-2017. Schier is also a Site Director of the Allen Discovery Center for Cell Lineage Tracing.

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[1][2].

In his own lab, Schier has made fundamental advances to the understanding of the molecular basis of vertebrate embryogenesis, including signaling[3][4][5][6][7][8][9][10], cell fate determination[4][5][11][12], cell movement[9], the maternal-zygotic transition[13][14], microRNAs[7][13][15], chromatin[16] and non-coding RNAs[17]. Schier’s more recent interest in behavior has established zebrafish as a model for sleep[18][19] and behavioral[20] research, determined neural circuits that underlie sleep[18] and identified small molecule sleep regulators[19].

He has contributed to the development of zebrafish as model system, including positional cloning[3], germ-line replacement to generate maternal-effect mutants[21], photobleaching and photo conversion[8], Brainbow imaging[12], brain activity atlas[22], small molecule profiling[19], transcriptomics[17][23] and epigenomics[16], gene annotation[9][17][24][25], CRISPR/Cas9 genome editing[26][27][28], and lineage tracing by genomic barcode editing[29].


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, Medical College of Georgia, MPI Tuebingen, IMP Vienna, University of Utah, and Cambridge University. Key to his mentoring philosophy are five questions he has developed to sharpen the thoughts of his mentees (see also [30]):

  • 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

References

  1. ↑ 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
  2. ↑ 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.
  3. 1 2 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.
  4. 1 2 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.
  5. 1 2 Chen, Y. and Schier, A.F. (2001). The zebrafish nodal signal squint functions as a morphogen. Nature 411, 607-610.
  6. ↑ 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.
  7. 1 2 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.
  8. 1 2 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.
  9. 1 2 3 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
  10. ↑ 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.
  11. ↑ 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
  12. 1 2 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
  13. 1 2 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.
  14. ↑ Schier AF (2007). "The Maternal-Zygotic Transition: Death and Birth of RNAs". Science 316 (5823): 406–7.
  15. ↑ 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.
  16. 1 2 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.
  17. 1 2 3 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.
  18. 1 2 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
  19. 1 2 3 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
  20. ↑ 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
  21. ↑ 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
  22. ↑ 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.
  23. ↑ 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.
  24. ↑ 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
  25. ↑ 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.
  26. ↑ 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
  27. ↑ 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.
  28. ↑ 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.
  29. ↑ 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.
  30. ↑ http://www.cell.com/current-biology/pdf/S0960-9822(04)00437-3.pdf
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