Hairballs and Other Sloppy Models
Posted January 05, 2010
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Overview
A major challenge in developmental biology is connecting a phenotypic description with the underlying chemistry. Mutations affect a mature organism in a variety of complex, interacting ways that are difficult to quantify, and classification can be subjective. For the most important molecular actors, mutations may prevent a mature organism from developing at all. Some researchers address these problems by studying the effects of a mutation on very early development. At a September 28, 2005, Academy symposium, the talks focused on systems biology approaches to characterizing complex phenotypes.
Topics discussed included a detailed mathematical model of interacting factors in the developing blastoderm of Drosophila, a network deduced from correlations between the phenotypic signatures of different genes in C. elegans, and how precisely the parameters of a model network can be determined and how they affect model predictions.
Use the tabs above to find a meeting report and multimedia from this event.
Web Sites
Flybase: A Database of the Drosophila Genome
The primary repository of genetic and molecular data of the insect family Drosophilidae. Maintained by the FlyBase consortium.
The Gene Ontology
The Gene Ontology (GO) database of annotated gene functional data for a variety of model organisms. GO provides a standardized controlled vocabulary organized into a structured ontology for the annotation of gene functions according to biological process, cellular compartment, and molecular function.
PhenoBank Database
Phenobank database of C. elegans RNAi phenotypes from Sönnichsen et al., focusing on the first two rounds of mitotic cell division. From Cenix Bioscience and Max Planck Institute, Dresden.
RNAi Database
Comprehensive database of RNA interference data for C. elegans. Includes raw time-lapse and image data, phenotypic annotations, RNAi-to-gene mappings, and tools for mining phenotypic data. Maintained by P. MacMenamin, K. Gunsalus, and F. Piano at NYU.
Stanford MicroArray Database
A database of transcription information for many model organisms.
Wormbase
Model organism database for information about C. elegans and related nematodes. Maintained by the WormBase consortium.
Books
Gilbert. S. F. 2000. Developmental Biology. 7th ed. Sinauer Associates, Sunderland, MA.
Hartenstein, V. 1995. Atlas of Drosophila Development. Cold Spring Harbor Laboratory Press, Woodbury, NY.
Journal Articles
Systems Biology in the Drosophila Blastoderm: What Can We Learn?
Aegerter-Wilmsen T., C. M. Aegerter & T. Bisseling. 2005. Model for the robust establishment of precise proportions in the early Drosophila embryo. J. Theor. Biol. 234: 13–19.
Arnosti, D. N., S. Barolo, M. Levine & S. Small. 1996. The eve stripe 2 enhancer employs multiple modes of transcriptional synergy. Development 122: 205–214. (PDF, 594 KB) Full Text
Frasch, M. & M. Levine. 1987. Complementary patterns of even-skipped and fushi tarazu expression involve their differential regulation by a common set of segmentation genes in Drosophila. Genes Dev. 1: 981–195.
Gray, S., H. Cai, S. Barolo & M. Levine. 1995. Transcriptional repression in the Drosophila embryo. Philos. Trans. R. Soc. Lond. B Biol. Sci. 349: 257–262.
Houchmandzadeh, B., E. Wieschaus & S. Leibler. 2002. Establishment of developmental precision and proportions in the early Drosophila embryo. Nature 415: 798–802.
Jaeger J., M. Blagov, K. N. Kozlov, et al. 2004. Dynamical analysis of regulatory interactions in the gap gene system of Drosophila melanogaster. Genetics 167: 1721–1737. Full Text
Jaeger J., S. Surkova, M. Blagov, et al. 2004. Dynamic control of positional information in the early Drosophila embryo. Nature 430: 368–371.
Meinhardt, H. 1988. Models for maternally supplied positional information and the activation of segmentation genes in Drosophila embryogenesis. Development 104: 95–110.
Merrill, P.T., D. Sweeton & E. Wieschaus. 1988. Requirements for autosomal gene activity during precellular stages of Drosophila melanogaster. Development 104: 495–509.
Mjolsness E., D. J. Sharp & J. Reinitz. 1991. A connectionist model of development. J. Theor. Biol. 152: 429–453.
Myasnikova E. A. Samsonova, K. Kozlov, et al. 2001. Support vector regression applied to the determination of the developmental age of a Drosophila embryo from its segmentation gene expression patterns. Bioinformatics 18: S87-S95. (PDF, 209.77 KB) Full Text
Howard, M. & P. Rein ten Wolde. 2005. Finding the center reliably: robust patterns of developmental gene expression. Phys. Rev. Lett. 95: 208103.
Reinitz, J., S. Hou & D. H. Sharp. 2003. Transcriptional control in Drosophila. ComPlexUs 1: 54–64.
Small S., A. Blair & M. Levine. 1992. Regulation of even-skipped stripe 2 in the Drosophila embryo. EMBO J. 11: 4047–4057. Full Text
Small S., D. N. Arnosti & M. Levine 1993. Spacing ensures autonomous expression of different stripe enhancers in the even-skipped promoter. Development 119: 762–772 (PDF, 69 KB) Full Text
Predictive Models of Molecular Machines Involved in C. elegans Early Embryogenesis
Brajenovic, M., G. Joberty, B. Kuster, et al. 2004. Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network. J. Biol. Chem. 279: 12804–12811. Full Text
Giot, L., J. S. Bader, C. Brouwer, et al. 2003. A protein interaction map of Drosophila melanogaster. Science 302: 1727–1736.
Gunsalus, K.C. & F. Piano 2005. RNAi as a tool to study cell biology: building the genome-phenome bridge. Curr. Opin. Cell Biol. 17: 3-8.
Gunsalus K.C. et al. 2005. Predictive models of molecular machines involved in Caenorhabditis elegans early embryogenesis. Nature 436: 861-5.
Hannak, E., M. Kirkham, A. A. Hyman & K. Oegema. 2001. Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans. J. Cell Biol. 155: 1109–1116. Full Text
Ideker, T. & D. Lauffenburger. 2003. Building with a scaffold: Emerging strategies for high- to low-level cellular modeling. Trends Biotechnol. 21: 255–262.
Kim, S. K., J. Lund, M. Kiraly, et al. 2001. A gene expression map for Caenorhabditis elegans. Science 293: 2087–2092.
Kirkham, M., T. Muller-Reichert, K. Oegema, et al. 2003. SAS-4 is a C. elegans centriolar protein that controls centrosome size. Cell 112: 575–587.
Leidel, S. & P. Gönczy. 2003. SAS-4 is essential for centrosome duplication in C. elegans and is recruited to daughter centrioles once per cell cycle. Dev. Cell 4: 431–439.
Li, S., C. M. Armstrong, N. Bertin, et al. 2004. A map of the interactome network of the metazoan C. elegans. Science 303: 540–543.
O'Connell, K.F. et al. 2001. The C. elegans zyg-1 gene encodes a regulator of centrosome duplication with distinct maternal and paternal roles in the embryo. Cell 105: 547–558.
Oltvai, Z. N. & A. L. Barabasi. 2002. Systems biology. Life's complexity pyramid. Science 298: 763–764.
Piano, F., A. J. Schetter, D. G. Morton, et al. 2002. Gene clustering based on RNAi phenotypes of ovary-enriched genes in C. elegans. Curr. Biol. 12: 1959–1964.
Sönnichsen, B., L. Koski, A. Walsh, et al. 2005. Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434: 462-469.
Sophisticated Statistical Mechanics of Sloppy Models: Making Predictions about Protein Dynamics in Cells
Brown, K. S., C. C. Hill, G. A. Calero, et al. 2004. The statistical mechanics of complex signaling networks: nerve growth factor signaling. Phys. Biol. 1: 184–195.
Brown, K. S., & J. P. Sethna. 2003. Statistical mechanical approaches to models with many poorly known parameters. Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 68: 021904.
Speakers
John Reinitz, PhD
Stony Brook University
e-mail | web site | publications
John Reinitz is a professor in the department of applied mathematics and statistics and at Stony Brook University (formerly the State University of New York, Stony Brook), where he is also a member of the Center for Developmental Genetics. His lab is investigating and developing models of Drosophila embryogenesis. Prior to coming to Stony Brook, Reinitz was on the faculty at Mt. Sinai School of Medicine. He received a PhD from Yale University, and did postdoctoral work at Columbia University and Yale.
Kris Gunsalus, PhD
New York University
e-mail | web site | publications
Kris Gunsalus is a research assistant professor in the biology department at New York University, and is a member of NYU's Center for Comparative Functional Genomics. In her work she develops tools to analyze diverse functional genomics data in order to identify groups of genes that work in specific cellular and developmental processes, particularly in C. elegans. She came to NYU from Cornell University, where she received her PhD in 1997.
Kevin S. Brown, PhD
Harvard University
e-mail | publications
Kevin Brown is a postdoc in Andrew Murray's lab in the department of molecular and cellular biology at Harvard University. He received a PhD in physics in 2003 from Cornell University.
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.