Alexander F. Schier

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Alexander F. Schier
AlexSchier.jpg
Alexander F. Schier (2017)
Born1964
Citizenship Switzerland, 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)
Election to Academia Europaea (2020)
AAAS Fellow, American Association for the Advancement of Science (2021) [2]
Scientific career
Fields Cell 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 advisor Walter J. Gehring
Other academic advisorsWolfgang Driever

Alexander F. Schier (born 1964) is a Professor of Cell Biology and the Director of the Biozentrum University of Basel, Switzerland. [3]

Contents

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. [4] [5]

In his own lab, Schier has made fundamental contributions to the understanding of the molecular basis of vertebrate embryogenesis, including signaling, [6] [7] [8] [9] [10] [11] [12] [13] cell fate determination, [7] [8] [14] [15] cell movement, [12] the maternal-zygotic transition, [16] [17] microRNAs, [10] [16] [18] chromatin [19] and non-coding RNAs. [20] Schier's more recent interest in behavior has established zebrafish as a model for sleep [21] [22] and behavioral [23] research, determined neural circuits that underlie sleep [21] identified small molecule sleep regulators [22] 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, [6] germ-line replacement to generate maternal-effect mutants, [24] photobleaching and photo conversion, [11] Brainbow imaging, [15] brain activity atlas, [25] small molecule profiling, [22] transcriptomics [20] [26] and epigenomics, [19] gene annotation, [12] [20] [27] [28] CRISPR/Cas9 genome editing, [29] [30] [31] lineage tracing by genomic barcode editing [32] and reconstruction of developmental trajectories by single-cell RNA-sequencing. [33]

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: [34]

Awards

Related Research Articles

Zebrafish Species of fish

The zebrafish is a freshwater fish belonging to the minnow family (Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio. It is also found in private ponds.

Lefty are a class of proteins that are closely related members of the TGF-beta superfamily of growth factors. These proteins are secreted and play a role in left-right asymmetry determination of organ systems during development. Mutations of the genes encoding these proteins have been associated with left-right axis malformations, particularly in the heart and lungs.

mir-10 microRNA precursor family

The miR-10 microRNA precursor is a short non-coding RNA gene involved in gene regulation. It is part of an RNA gene family which contains miR-10, miR-51, miR-57, miR-99 and miR-100. miR-10, miR-99 and miR-100 have now been predicted or experimentally confirmed in a wide range of species. mir-51 and mir-57 have currently only been identified in the nematode Caenorhabditis elegans.

Nodal homolog

Nodal homolog is a secretory protein that in humans is encoded by the NODAL gene which is located on chromosome 10q22.1. It belongs to the transforming growth factor beta (TGF-β) superfamily. Like many other members of this superfamily it is involved in cell differentiation in early embryogenesis, playing a key role in signal transfer from the primitive node, in the anterior primitive streak, to lateral plate mesoderm (LPM).

The Nodal signaling pathway is a signal transduction pathway important in regional and cellular differentiation during embryonic development.

Maternal to zygotic transition is the stage in embryonic development during which development comes under the exclusive control of the zygotic genome rather than the maternal (egg) genome. The egg contains stored maternal genetic material mRNA which controls embryo development until the onset of MZT. After MZT the diploid embryo takes over genetic control. This requires both zygotic genome activation (ZGA) and degradation of maternal products. This process is important because it is the first time that the new embryonic genome is utilized and the paternal and maternal genomes are used in combination. The zygotic genome now drives embryo development.

mir-451 microRNA

In molecular biology mir-451 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-430 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

Biozentrum University of Basel Division of the University of Basel

The Biozentrum of the University of Basel specializes in basic molecular and biomedical research and teaching. Research includes the areas of cell growth and development, infection biology, neurobiology, structural biology and biophysics, and computational and systems biology. With 500 employees, the Biozentrum is the largest department at the University of Basel's Faculty of Science. It is home to 30 research groups with scientists from more than 40 nations.

The ZebraBox is the first ever automated analysis chamber used for zebrafish monitoring in a non-intrusive manner.

<i>Bicoid</i> (gene) Protein-coding gene in the species Drosophila melanogaster

Bicoid is a maternal effect gene whose protein concentration gradient patterns the anterior-posterior (A-P) axis during Drosophila embryogenesis. Bicoid was the first protein demonstrated to act as a morphogen. Although Bicoid is important for the development of Drosophila and other higher dipterans, it is absent from most other insects, where its role is accomplished by other genes.

Template-switching polymerase chain reaction (TS-PCR) is a method of reverse transcription and polymerase chain reaction (PCR) amplification that relies on a natural PCR primer sequence at the polyadenylation site, also known as the poly(A) tail, and adds a second primer through the activity of murine leukemia virus reverse transcriptase. This permits reading full cDNA sequences and can deliver high yield from single sources, even single cells that contain 10 to 30 picograms of mRNA, with relatively low levels (3-5%) of contaminating rRNA sequence. This technique is often employed in whole transcriptome shotgun sequencing. It is marketed by Clontech as Switching Mechanism At the 5' end of RNA Template (SMART) as well as by Diagenode as Capture and Amplification by Tailing and Switching (CATS).

Debora S. Marks is a researcher in computational biology and an Associate Professor of Systems Biology at Harvard Medical School. Her research uses computational approaches to address a variety of biological problems.

Didier Stainier

Didier Stainier is a Belgian/American developmental geneticist who is currently a director at the Max Planck Institute for Heart and Lung Research in Bad Nauheim, Germany.

A. James Hudspeth

A. James Hudspeth is the F.M. Kirby Professor at Rockefeller University, where he is director of the F.M. Kirby Center for Sensory Neuroscience. His laboratory studies the physiological basis of hearing.

Antonio Jesus Giraldez is a Spanish developmental biologist and RNA researcher at Yale University School of Medicine, where he serves as chair of the department of genetics and Fergus F. Wallace Professor of Genetics. He is also affiliated with the Yale Cancer Center and the Yale Stem Cell Center.

Micropeptide Short length polypeptides

Micropeptides are polypeptides with a length of less than 100-150 amino acids that are encoded by short open reading frames (sORFs). In this respect, they differ from many other active small polypeptides, which are produced through the posttranslational cleavage of larger polypeptides. In terms of size, micropeptides are considerably shorter than "canonical" proteins, which have an average length of 330 and 449 amino acids in prokaryotes and eukaryotes, respectively. Micropeptides are sometimes named according to their genomic location. For example, the translated product of an upstream open reading frame (uORF) might be called a uORF-encoded peptide (uPEP). Micropeptides lack an N-terminal signaling sequences, suggesting that they are likely to be localized to the cytoplasm. However, some micropeptides have been found in other cell compartments, as indicated by the existence of transmembrane micropeptides. They are found in both prokaryotes and eukaryotes. The sORFs from which micropeptides are translated can be encoded in 5' UTRs, small genes, or polycistronic mRNAs. Some micropeptide-coding genes were originally mis-annotated as long non-coding RNAs (lncRNAs).

Kenneth Poss American biologist (born 1971)

Kenneth D. Poss is an American biologist and currently James B. Duke Professor of Cell Biology and director of the Regeneration Next Initiative at the Duke University School of Medicine.

Andrew Oates Australian-British embryologist

Andrew 'Andy' Charles Oates is an Australian and British developmental biologist and embryologist specialized in biological pattern formation. He is professor at EPFL and head of the Segmentation Timing and Dynamics Laboratory at EPFL's School of Life Sciences. Since 2021, he has been dean of EPFL's School of Life Sciences.

Andrea Pauli is a developmental biologist and biochemist studying how the egg transitions into an embryo, and more specifically the molecular mechanisms underlying vertebrate fertilisations, egg dormancy, and subsequent egg activation.. Her lab uses zebrafish as the main model organism. Andrea Pauli is a group leader at the Research Institute of Molecular Pathology (IMP) at the Vienna Biocenter in Austria.

References

  1. Science Breakthrough of the Year (2018) harvard.edu Retrieved 2019-12-12
  2. 2021 AAAS Fellows aaas.org Retrieved 2022-01-26
  3. Alex Schier Appointed New Director of the Biozentrum unibas.ch Retrieved 2019-12-12
  4. 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
  5. 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.
  6. 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.
  7. 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.
  8. 1 2 Chen, Y. and Schier, A.F. (2001). The zebrafish nodal signal squint functions as a morphogen. Nature 411, 607-610.
  9. 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.
  10. 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.
  11. 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.
  12. 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
  13. Dubrulle, Julien; Jordan, Benjamin M; Akhmetova, Laila; Farrell, Jeffrey A; Kim, Seok-Hyung; Solnica-Krezel, Lilianna; Schier, Alexander F (14 April 2015). "Response to Nodal morphogen gradient is determined by the kinetics of target gene induction". eLife. 4: e05042. doi:10.7554/eLife.05042. PMC   4395910 . PMID   25869585.
  14. Huang, Peng; Xiong, Fengzhu; Megason, Sean G.; Schier, Alexander F. (7 June 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. PMC   3369957 . PMID   22685423.
  15. 1 2 Pan, Y. Albert; Freundlich, Tom; Weissman, Tamily A.; Schoppik, David; Wang, X. Cindy; Zimmerman, Steve; Ciruna, Brian; Sanes, Joshua R.; Lichtman, Jeff W.; Schier, Alexander F. (1 July 2013). "Zebrabow: multispectral cell labeling for cell tracing and lineage analysis in zebrafish". Development. 140 (13): 2835–2846. doi:10.1242/dev.094631. PMC   3678346 . PMID   23757414.
  16. 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.
  17. Schier AF (2007). "The Maternal-Zygotic Transition: Death and Birth of RNAs". Science 316 (5823): 406–7.
  18. 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.
  19. 1 2 Vastenhouw, Nadine L.; Zhang, Yong; Woods, Ian G.; Imam, Farhad; Regev, Aviv; Liu, X. Shirley; Rinn, John; Schier, Alexander F. (8 April 2010). "Chromatin signature of embryonic pluripotency is established during genome activation". Nature. 464 (7290): 922–926. Bibcode:2010Natur.464..922V. doi:10.1038/nature08866. PMC   2874748 . PMID   20336069.
  20. 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.
  21. 1 2 Prober, D. A.; Rihel, J.; Onah, A. A.; Sung, R.-J.; Schier, A. F. (20 December 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. PMC   6675014 . PMID   17182791.
  22. 1 2 3 Rihel, Jason; Prober, David A.; Arvanites, Anthony; Lam, Kelvin; Zimmerman, Steven; Jang, Sumin; Haggarty, Stephen J.; Kokel, David; Rubin, Lee L.; Peterson, Randall T.; Schier, Alexander F. (15 January 2010). "Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation". Science. 327 (5963): 348–351. Bibcode:2010Sci...327..348R. doi:10.1126/science.1183090. PMC   2830481 . PMID   20075256.
  23. Woods, I. G.; Schoppik, D.; Shi, V. J.; Zimmerman, S.; Coleman, H. A.; Greenwood, J.; Soucy, E. R.; Schier, A. F. (26 February 2014). "Neuropeptidergic Signaling Partitions Arousal Behaviors in Zebrafish". Journal of Neuroscience. 34 (9): 3142–3160. doi:10.1523/JNEUROSCI.3529-13.2014. PMC   3935080 . PMID   24573274.
  24. Ciruna, B.; Weidinger, G.; Knaut, H.; Thisse, B.; Thisse, C.; Raz, E.; Schier, A. F. (12 November 2002). "Production of maternal-zygotic mutant zebrafish by germ-line replacement". Proceedings of the National Academy of Sciences. 99 (23): 14919–14924. Bibcode:2002PNAS...9914919C. doi: 10.1073/pnas.222459999 . PMC   137520 . PMID   12397179.
  25. 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.
  26. 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.
  27. Chew, Guo-Liang; Pauli, Andrea; Rinn, John L.; Regev, Aviv; Schier, Alexander F.; Valen, Eivind (1 July 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. PMC   3678345 . PMID   23698349.
  28. 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.
  29. Gagnon, James A.; Valen, Eivind; Thyme, Summer B.; Huang, Peng; Ahkmetova, Laila; Pauli, Andrea; Montague, Tessa G.; Zimmerman, Steven; Richter, Constance; Schier, Alexander F. (29 May 2014). "Efficient Mutagenesis by Cas9 Protein-Mediated Oligonucleotide Insertion and Large-Scale Assessment of Single-Guide RNAs". PLOS ONE. 9 (5): e98186. Bibcode:2014PLoSO...998186G. doi: 10.1371/journal.pone.0098186 . PMC   4038517 . PMID   24873830.
  30. 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.
  31. 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.
  32. 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.
  33. 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.
  34. Schier, Alexander (July 2004). "Q & A". Current Biology. 14 (13): R494. doi: 10.1016/j.cub.2004.06.032 . PMID   15242623. S2CID   235312071.