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Visiting Professor of Molecular and Cellular Biology

Alex Schier

Visiting Professor of Molecular and Cellular Biology

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Our research addresses two questions:

(i) vertebrate embryogenesis-how do signals, non-coding RNAs, and chromatin influence the fate and movement of cells?

(ii) behavior – how do neuropeptides and neural circuits regulate locomotion, sleep, and learning?

We mainly use zebrafish as a model system, because genetic and imaging approaches can be combined to study complex behaviors and developmental processes in a vertebrate.

1. Vertebrate embryogenesis

The vertebrate body plan is set up during gastrulation, when a ball of undifferentiated, totipotent cells is transformed into an embryo. This process results in the formation of the three germ layers (ectoderm, mesoderm, and endoderm) and the three axes (anterior-posterior, dorsal-ventral and left-right). We wish to understand how signaling pathways, transcription factors, chromatin modifications and non-coding RNAs regulate this process. We are using genetic, biophysical and in vivo imaging approaches to determine how signals move through fields of cells, elicit concentration dependent effects and modulate the fate and migration of cells. In parallel, we use genomic and genetic approaches to determine how chromatin modifications and non-coding RNAs regulate early development.

2. Behavior

The genetic and cellular mechanisms that control sleep and wake states remain largely elusive. We have established zebrafish as a model system for sleep research. Zebrafish have the basic hallmarks of sleep-like behaviors. Sleeping fish require stronger stimuli than awake fish to initiate movement and sleep deprivation is followed by increased sleep. In addition, the zebrafish brain expresses peptides that have been implicated in human sleep disorders. We are using genetic and pharmacological screens to isolate sleep regulators and use imaging approaches to dissect sleep circuits. More recently, we have begun to develop assays for learning and memory in zebrafish and have used calcium imaging to identify neurons involved in learning.

Selected Publications

McKenna A, Findlay GM, Gagnon JA, Horwitz MS, Schier AF, Shendure J. (2016) Whole-organism lineage tracing by combinatorial and cumulative genome editingScience 353, 6298: aaf7907. doi: 10.1126/science.aaf7907. PMID:  27229144

Randlett O, Wee CL, Naumann EA, Nnaemeka O, Schoppik D, Fitzgerald JE, Portugues R, Lacoste AM, Riegler C, Engert F, Schier AF. (2015) Whole-brain activity mapping onto a zebrafish brain atlas.  Nat Methods 12(11), 1039-46.

Woods, I.G., Schoppik, D., Shi, V.J., Zimmerman, S., Coleman, H.A., Greenwood, J., Soucy, E.R., and Schier, A.F. (2014) Neuropeptidergic signaling partitions arousal behaviors in zebrafish. Journal of Neuroscience 34, 3142-60

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

Müller, 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.

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.

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.

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.