Networks of interacting genes control a variety of fundamental biological processes, including embryonic development, cell division, and cell death. Understanding the function of an entire network of genes which control development is a central problem of functional genomics and systems biology. Although general technology to solve the problem does not yet exist, it can be solved today for the network of genes which control the segmentation system of Drosophila melanogaster. The research plan to accomplish this goal is an integrated program of experimentation and computational modeling, which will be used to characterize the process by which positional information encoded in maternal gradients is transformed into precise and stable expression of the segment polarity genes engrailed and wingless in stripes one nucleus in width. This process creates an extremely precise spatial body plan from imprecise maternal cues. Early patterns containing considerable noise and variation between individuals are transformed into highly precise late patterns with little variation. The work proposed will result in a realistic and predictive theory of pattern formation and error correction in the morphogenetic field that determines Drosophila segmentation.
Our specific aims are to 1) Make use of a family of chemical kinetic models to understand the typical expression and the dynamics of the segmentation genes in wild type and mutants up the initiation of wg and en expression. 2) Exploit these models to gain deeper understanding of robustness, both in a natural context and under stress 3) Perform quantitative live imaging studies of zygotic segmentation genes, supplemented by fixed tissue data from mutants. 4.) Develop new tools to support Aims 1-3 and make them, together with all data, models, and code available to the scientific community through the FlyEx database
This project concerns basic science with long term implications for translational science and medicine. It is concerned with the genetics of development, the scientific understanding of which is a precondition for understanding cancer and birth defects. The project also aims at a precise understanding of canalization in development, an """"""""error correction"""""""" process that is closely related to wound healing and regeneration.
|Bertolino, Eric; Reinitz, John; Manu (2016) The analysis of novel distal Cebpa enhancers and silencers using a transcriptional model reveals the complex regulatory logic of hematopoietic lineage specification. Dev Biol 413:128-44|
|Lou, Zhihao; Reinitz, John (2016) Parallel Simulated Annealing Using an Adaptive Resampling Interval. Parallel Comput 53:23-31|
|Kozlov, Vladimir; Vakulenko, Sergey; Wennergren, Uno (2016) Hamiltonian dynamics for complex food webs. Phys Rev E 93:032413|
|Jiang, Pengyao; Ludwig, Michael Z; Kreitman, Martin et al. (2015) Natural variation of the expression pattern of the segmentation gene even-skipped in melanogaster. Dev Biol 405:173-81|
|Ramos, Alexandre F; Hornos, JosÃ© Eduardo M; Reinitz, John (2015) Gene regulation and noise reduction by coupling of stochastic processes. Phys Rev E Stat Nonlin Soft Matter Phys 91:020701|
|Martinez, Carlos; Rest, Joshua S; Kim, Ah-Ram et al. (2014) Ancestral resurrection of the Drosophila S2E enhancer reveals accessible evolutionary paths through compensatory change. Mol Biol Evol 31:903-16|
|Grigoriev, D; Reinitz, J; Vakulenko, S et al. (2014) Punctuated evolution and robustness in morphogenesis. Biosystems 123:106-13|
|Kim, Ah-Ram; Martinez, Carlos; Ionides, John et al. (2013) Rearrangements of 2.5 kilobases of noncoding DNA from the Drosophila even-skipped locus define predictive rules of genomic cis-regulatory logic. PLoS Genet 9:e1003243|
|Surkova, Svetlana; Golubkova, Elena; Manu et al. (2013) Quantitative dynamics and increased variability of segmentation gene expression in the Drosophila Kruppel and knirps mutants. Dev Biol 376:99-112|
|Lopes, Francisco J P; Spirov, Alexander V; Bisch, Paulo M (2012) The role of Bicoid cooperative binding in the patterning of sharp borders in Drosophila melanogaster. Dev Biol 370:165-72|
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