Growth Networks: Systems Biology Meets Developmental Biology
Posted January 10, 2010
Development involves dramatic and predictable gene expression changes that provide powerful insight into the underlying biological networks. At a November 19, 2009, meeting at the Academy, speakers described how these dramatic changes illuminate three important topics: transcriptional regulation, protein phosphorylation, and stem cells and cancer.
Angela DePace discussed high-spatial-resolution mapping of Drosophila embryos that gives a wealth of quantitative data for developing models of gene regulation. Stanislav Shvartsman showed that MAP kinase, the endpoint of a highly conserved protein phosphorylation cascade, features a common docking site for kinases that phosphorylate it, phosphatases that dephosphorylate it, and substrates that it acts on. Antonio Iavarone described how systems biology analysis helps to identify specific molecular pathways that lead cells to remain in a stem-cell state or to begin differentiation.
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Berkeley Drosophila Transcription Network Project
The Berkeley Drosophila Transcription Network Project is a multidisciplinary team at Lawrence Berkeley National Laboratory, the University of California, Berkeley, and the University of California, Davis. Their goal is to decipher the transcriptional information contained in the extensive cis-acting DNA sequences that direct the patterns of gene expression that underlie animal development. Using the early embryo of the fruitfly Drosophila melanogaster as a model, they are developing experimental and computational methods to systematically characterize and dissect the complex expression patterns and regulatory interactions already present prior to gastrulation.
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Luengo Hendriks CL, Keränen SV, Fowlkes CC, et al. 2006. Three-dimensional morphology and gene expression in the Drosophila blastoderm at cellular resolution I: data acquisition pipeline. Genome Biol. 7: R123. Full Text
Weber GH, Rübel O, Huang MY, et al. 2009. Visual exploration of three-dimensional gene expression using physical views and linked abstract views. IEEE/ACM Trans. Comput. Biol. Bioinform. 6: 296-309.
Berezhkovskii AM, Coppey M, Shvartsman SY. 2009. Signaling gradients in cascades of two-state reaction-diffusion systems. Proc. Natl. Acad. Sci. USA 106: 1087-1092. Full Text
Lembong J, Yakoby N, Shvartsman SY. 2009. Pattern formation by dynamically interacting network motifs. Proc. Natl. Acad. Sci. USA 106: 3213-3218. Full Text
Shvartsman SY, Coppey M, Berezhkovskii AM. 2009. MAPK signaling in equations and embryos. Fly (Austin) 3: 62-67. Full Text
Carro MS, Lim WK, Alvarez MJ, et al. 2009. The transcriptional network for mesenchymal transformation of brain tumours. Nature [Epub ahead of print]
Iavarone A, Lasorella A. 2006. ID proteins as targets in cancer and tools in neurobiology. Trends Mol. Med. 12: 588-594.
Zhao X, D' Arca D, Lim WK, et al. 2009. The N-Myc-DLL3 cascade is suppressed by the ubiquitin ligase Huwe1 to inhibit proliferation and promote neurogenesis in the developing brain. Dev. Cell 17: 210-221.
Zhao X, Heng JI, Guardavaccaro D, et al. 2008. The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein. Nat. Cell Biol. 10:643-653. Full Text
Angela DePace, PhD
Angela DePace received her PhD in Biochemistry from the University of California, San Francisco in 2002, where she worked with Jonathan Weissman on the molecular mechanism of yeast prion propagation. By measuring the growth of individual prion fibers she was able to demonstrate that a single protein can fold into multiple pathogenic conformations, each giving rise to different phenotypes, providing powerful evidence for the protein-only hypothesis. As a Helen Hay Whitney postdoctoral fellow, she worked with Michael Eisen at UC, Berkeley, and as part of the Berkeley Drosophila Transcription Network Project to apply 2-photon microscopy and image processing techniques to characterize the transcriptional network directing embryonic development of multiple species of Drosophila. She started her own lab in the Department of Systems Biology at Harvard Medical School in April 2008, where her group is broadly interested in the molecular mechanisms of gene regulation and how they shape evolution of regulatory networks.
Stanislav Y. Shvartsman, PhD
Stanislav Shvartsman was born in Odessa (Ukraine) and received his undergraduate degree in physical chemistry from the Moscow State University in Russia. His graduate degrees are in chemical engineering from Technion and Princeton. After postdoctoral work at MIT, he opened his laboratory at the Lewis-Sigler Institute for Integrative Genomics at Princeton. The Shvartsman lab combines genetic, imaging, and computational approaches to study pattern formation and morphogenesis. The model system is Drosophila development and the main emphasis is on the direct connection between experiment and theory.
Antonio Iavarone, MD
Antonio Iavarone is an associate professor at the Institute for Cancer Genetics and the Departments of Neurology and Pathology of Columbia University Medical Center, New York. He received an MD degree and Pediatric Residency from the Catholic University of Rome. He was a research fellow at the University of California at San Francisco and the Memorial Sloan Kettering Cancer Center, New York. In 1998, he joined the Faculty of Neurology and Developmental and Molecular Biology at the Albert Einstein College of Medicine, New York. He assumed his current position in 2002. His research has focused on delineating the role of Id2 and the retinoblastoma tumor-suppressor protein in development and pediatric cancer of the nervous system. His lab is collaborating with Andrea Califano's group at Columbia University on the identification of master regulatory factors in neural development and brain tumors.
Don Monroe is a science writer based in Murray Hill, New Jersey. After getting a PhD in physics from MIT, he spent more than fifteen years doing research in physics and electronics technology at Bell Labs. He writes on physics, technology, and biology.