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  Location: Home >> Faculty >> Molecular Systems Biology
  Molecular Systems Biology

Zhuo Du

Education and Training
1999-2003, B.S. in Biotechnology, Hunan Agricultural University;
2003-2008, Ph.D. in Biochemistry and Molecular Biology, China Agricultural University;
2008-2009, Postdoctoral Training in Cell Biology, Albert Einstein College of Medicine;
2009-2014, Postdoctoral Training in Developmental Biology, Memorial Sloan Kettering Cancer Center;
2015-, Principle Investigator, Institute of Genetics and Developmental Biology, CAS

Research Interests
Our group investigates how genotype dictates complex phenotypes, using C. elegans embryogenesis as a model. We are applying live imaging and automated phenotyping to quantify developmental phenotypes at single-cell resolution and using phenotypic data to infer how genome and regulatory networks operate at molecular, cellular, and tissue/organ levels to drive complex in vivo development.

Our recent progresses (during my postdoctoral training) have provided a solid basis for above goals.
First, we have established an automated phenotyping system to quantify developmental phenotypes for individual cells. It relies on long term 3D time-lapse recording of embryogenesis followed by transformation of 4D images into quantitative measurements of individual cell’s developmental behaviors such as gene expression, proliferation, differentiation and morphogenesis. The system allows acquisition and processing of 3,000 to 5,000 mutant embryos each year.

Second, we have devised an automated phenotype reasoning strategy to transform massive phenotypic data into succinct mechanistic models of cell fate regulation. In a proof-of-concept study, we have successfully reconstructed a systems-wide mechanistic model on how gene modules and cell-to-cell signaling events regulate series of cell fate choices in the early embryos.

Third, we have completed a systematic functional profiling of hundreds of conserved regulatory genes that are essential for embryogenesis. Functional analysis of phenotypic data has revealed systems properties of cell fate regulation and identified a large number of master switches of cell fate decision. Integrative network inference allows construction of a multiscale (geneàcellàdifferentiation) regulatory network that predicts how molecular networks regulate cell fates on the differentiation landscape. Together, these developments provide a unique opportunity to investigate the function of every gene in every cell at every developmental stage.

In general, we are very interested in two types of studies: first, applying systems biology strategies and approaches to address developmental biology questions, and second, understanding general principles/logic of genome biology and developmental biology. The ongoing projects will be focusing on but not limited to: (1) pursuing single-cell quantitative analysis of development; (2) mapping cell-specific genetic interaction networks; (3) elucidating mechanisms of in vivo cell fate regulation and (4) understanding molecular and cellular basis of developmental robustness.

Selected Publications:
Du Z, He F, Yu Z, Bowerman B, Bao Z, E3 ubiquitin ligases promote progression of differentiation during C. elegans embryogenesis. Dev Biol. In press
Du Z, Stantella A., He F., Tiongson M, Bao Z. De novo inference of systems-level mechanistic models of development from live imaging-based phenotype analysis. Cell. 2014 Jan 16;156(1-2):359-72.
Moore JL, Du Z, Bao Z. Systematic quantification of developmental phenotypes at single-cell resolution during embryogenesis. Development. 2013 Aug;140(15):3266-74.
Wu Y, Ghitani A, Christensen R, Santella A, Du Z, Rondeau G, Bao Z, Colón-Ramos D, Shroff H. Inverted selective plane illumination microscopy (iSPIM) enables coupled cell identity lineaging and neurodevelopmental imaging in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17708-13.
Schultz SS, Desbordes SC, Du Z, Kosiyatrakul S, Lipchina I, Studer L, Schildkraut CL. Single-molecule analysis reveals changes in the DNA replication program for the POU5F1 locus upon human embryonic stem cell differentiation. Mol Cell Biol. 2010 Sep;30(18):4521-34.
Du Z, Zhao Y, Li N. Genome-wide colonization of gene regulatory elements by G4 DNA motifs.  Nucleic Acids Res. 2009 Nov;37(20):6784-98.
Du Z, Zhao Y, Li N. Genome-wide analysis reveals regulatory role of G4 DNA in gene transcription. Genome Res. 2008 Feb;18(2):233-41.