My laboratory is engaged in a long term project to understand how DNA sequence specifies biological form. We are interested not only in the specification of typical form by a typical genome, but also in the effects of variability. Such variability might take the form of genetic variation in a population or intrinsic fluctuations in an individual. These problems touch on issues central to developmental and evolutionary biology, and efforts to solve them have previously led to the development of new branches of mathematics.
We consider these issues in the specific context of segment determination in the fruit fly Drosophila melanogaster , but actively seek collaborations with investigators working on other organisms or with pure theoreticians. The starting point for our own investigations are quantitative data on gene expression, extracted from images of confocally scanned fixed or living embryos. We use this numerical information to find parameter sets for specific models of fundamental processes of gene regulation and pattern formation by means of large scale optimization procedures performed on parallel computers. These models may be specified in terms of DNA sequence or be more coarse-grained. They might take the form of a dynamical system, deterministic or stochastic, or simply be a complex but explicit mathematical function.
Our goal is to use every tool in the toolbox—wet experiments, statistics, computational science, and mathematics—to solve a well focused scientific problem: how does a fly go from DNA sequence to a fate map of presumptive segments at single cell resolution?
Manu, Surkova S, Spirov AV, Gursky VV, Janssens H, Kim AR, Radulescu O, Vanario-Alonso CE, Sharp DH, Samsonova M, Reinitz J. Canalization of gene expression in the Drosophila blastoderm by gap gene cross regulation. PLoS Biol. 2009 Mar;7(3):e1000049. (PubMed)
Manu, Surkova S, Spirov AV, Gursky VV, Janssens H, Kim AR, Radulescu O, Vanario-Alonso CE, Sharp DH, Samsonova M, Reinitz J. Canalization of gene expression and domain shifts in the Drosophila blastoderm by dynamical attractors. PLoS Comput Biol. 2009 Mar;5(3):e1000303. (PubMed)
Surkova S, Kosman D, Kozlov K, Manu, Myasnikova E, Samsonova AA, Spirov A, Vanario-Alonso CE, Samsonova M, Reinitz J. Characterization of the Drosophila segment determination morphome. Dev Biol. 2008 Jan 15;313(2):844-62. (PubMed)
Reinitz J. Developmental biology: a ten per cent solution. Nature. 2007 Jul 26;448(7152):420-1. (PubMed)
Janssens H, Hou S, Jaeger J, Kim AR, Myasnikova E, Sharp D, Reinitz J. Quantitative and predictive model of transcriptional control of the Drosophila melanogaster even skipped gene. Nat Genet. 2006 Oct;38(10):1159-65. (PubMed)
Janssens H, Kosman D, Vanario-Alonso CE, Jaeger J, Samsonova M, Reinitz J. A high-throughput method for quantifying gene expression data from early Drosophila embryos. Dev Genes Evol. 2005 Jul;215(7):374-81. (PubMed)
Jaeger J, Blagov M, Kosman D, Kozlov KN, Manu, Myasnikova E, Surkova S, Vanario-Alonso CE, Samsonova M, Sharp DH, Reinitz J. Dynamical analysis of regulatory interactions in the gap gene system of Drosophila melanogaster. Genetics. 2004 Aug;167(4):1721-37. (PubMed)
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