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overview
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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?
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