ALEX F SCHIER
Mail: BL 1029
The Biological Labs
16 Divinity Ave
Cambridge, MA 02138
Schier Lab Website
MCB News Profile
Members of the Schier Lab
List of Publications from PubMed
Term: Fall Term; Repeated Spring Term 2013-2014. Credit: Half course.
Instructor: Alexander Schier
Course Level: Graduate Course
Our research addresses three questions:>
(i) what is the molecular basis of embryogenesis?
(ii) how does an organism sense potentially harmful stimuli?
(iii) what are the genes and circuits that regulate sleep and wakefulness?
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 and elicit concentration dependent effects. In parallel, we use biochemical and genetic approaches to determine how chromatin modifications and non-coding RNAs regulate early development.
2. Sensory neuron development and function
Animals protect themselves by sensing potentially harmful thermal, mechanical or chemical stimuli. This process of nociception is mediated by specific sensory receptors and circuits. We analyze the development and function of trigeminal sensory neurons, the primary nociceptors in the vertebrate head. We are using genetic and imaging approaches to study the molecules that regulate neuronal interactions and morphologies. In addition, we have begun to use in vivo imaging approaches and serial EM reconstruction to determine how different stimuli are encoded in the trigeminal ganglion and hindbrain.
3. Sleep and wakefulness
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 electrophysiological and imaging approaches to dissect sleep circuits.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.