PZhuPeixin Zhu, PhD
(Co-Mentor: Mark C. Fishman, MD)

Chemical Biology & Therapeutics
Cambridge, Massachusetts, United States

Much of the research in our group is driven by a desire to understand animal behavior at a fundamental genetic level. Our goal is to use genetics to dissect behavior in zebrafish by taking advantage of new tools to map relevant circuits in vivo. In particular, we are interested in the control of social behavior, the interaction of individuals, and control of the internal environment of the animal, for example, of cardiovascular physiology. The hope is that over the long term these may serve as systems relevant to drug discovery. We have begun exploratory projects such as setting up behavioral screens and using CRISPR-induced mutations of genes known to be associated with autism and schizophrenia. Projects include additional CRISPR genome editing as well as ENU-induced random mutagenesis, combined with behavioral assays in adult zebrafish. Targeted mutations have the additional power of permitting directed epistatic screens. These observations may have relevance to mental and cognitive disorders, and to the autonomic dysfunction that characterizes many diseases. One of the mentors (Mark C. Fishman) has extensive experience with zebrafish screens. And we will apply neural network mapping tools designed by one of the mentors (Peixin Zhu) to analyze functional connectivity and synaptic transmission deficiency of mutants with relevant phenotypes; these analyses involve use of high spatiotemporal resolution imaging and optogenetics. One of the mentors (MCF) has shown that such sensitized systems may be of value for screening of potentially corrective compounds.

Selected Publications

Peixin Zhu has a strong background in functional in vivo imaging and electrophysiology, and published peer-reviewed articles addressing computational mechanisms for sensory information representation in the vertebrate brain. The following are selected recent publications:

Equalization of odor representations by a network of electrically coupled inhibitory interneurons.
Zhu P, Frank T, Friedrich RW.
Nat Neurosci. 2013 Nov;16(11):1678-86. doi: 10.1038/nn.3528. Epub 2013 Sep 29.

High-resolution optical control of spatiotemporal neuronal activity patterns in zebrafish using a digital micromirror device.
Zhu P, Fajardo O, Shum J, Zhang Schärer YP, Friedrich RW.
Nat Protoc. 2012 Jun 28;7(7):1410-25. doi: 10.1038/nprot.2012.072

Circuit neuroscience in zebrafish.
Friedrich RW, Jacobson GA, Zhu P.
Curr Biol. 2010 Apr 27;20(8):R371-81. doi: 10.1016/j.cub.2010.02.039. Review

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Mark C. Fishman has mentored over 80 post-docs and published over 180 peer-reviewed scientific articles, including the original ENU zebrafish screens and the following selected recent publications:

Power of rare diseases: found in translation.
Fishman MC.
Sci Transl Med. 2013 Sep 4;5(201):201ps11. doi: 10.1126/scitranslmed.3006800

Designing zebrafish chemical screens.
Peterson RT, Fishman MC.
Methods Cell Biol. 2011;105:525-41. doi: 10.1016/B978-0-12-381320-6.00023-0.

High-throughput assay for small molecules that modulate zebrafish embryonic heart rate.
Burns CG, Milan DJ, Grande EJ, Rottbauer W, MacRae CA, Fishman MC.
Nat Chem Biol. 2005 Oct;1(5):263-4. Epub 2005 Sep 18

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