MBI Announces 200809 Theme: Mathematical Challenges in Developmental Biology

July 10, 2008

"The focus of the academic year 200809 program of the Mathematical Biosciences Institute at Ohio State University will be Mathematical Challenges in Developmental Biology," says MBI director Avner Friedman. "The year program will feature a broad range of themes, such as tissue movement, morphogenesis and limb growth, neural tube formation, neuroscience in early development, and pattern formation." Workshop participants will also consider related topics, including Drosophila development, regeneration of a tissue, cancer, and angiogenesis. Mathematics already plays an important role in all these areas, but new challenges abound.

Hans Othmer, one of the organizers of the year-long program, points out that much has been learned in the last two decades about the molecular components involved in signal transduction and gene expression in a number of systems. The focus is now shifting, he says, to understanding how these components are integrated into networks, and how these networks transduce the inputs they receive and produce the desired pattern of gene expression. "Theoreticians can contribute to an understanding of the relationship between network topology and functionality, and to the development of mathematical and computational tools for simulating growth, cell movement, and differentiation in developing systems."

Leah Edelstein-Keshet is a co-organizer of a workshop on cell and tissue movement. "The signal transduction pathways involved in cellular polarization and movement in eukaryotic cells, and polarity and differentiation in plants, will be important themes of our workshop," she says. "Such issues are important to morphogenesis in both animals and plants. They are also central in wound healing and invasive cancer." The organizers have designed the workshop to bridge the scales between the level of subcellular molecular mechanisms and the level of tissue functionality.

Neuroscience in early development is another topic that will be considered during the year. In the mammalian nervous system, a classic example of pattern formation is the formation of "maps." "Theories of map formation generally involve an interplay between a number of elements," says Ken Miller, an organizer of the annual program; "one example is the topographic matching of molecular gradients across axons and across the target structure." In recent years, Miller explains, "great progress has been made in elucidating the molecules involved in topographic map formation." The many remaining open questions include the computational function of observed learning rules, and the ability of different nearby neurons to learn to detect quite diverse features from the same overall set of inputs.

Wound healing and cancer, two topics that will be featured in the MBI program, have in common the underlying biological process of "angiogenesis," the formation of new blood vessels from existing vessels. As a tumor grows, it requires more oxygen for its new cells and so secretes growth factors that induce angiogenesis. Similarly, wound healing requires the formation of new blood vessels that will move into the wound. Kristin Swanson, an organizer of a workshop on cancer and angiogenesis, plans "to bring into the workshop mathematical modelers and state-of-the-art experimentalists and clinician-scientists to discuss every level of tumor growth." Philip Maini, an organizer of the workshop on wound healing, says that "to arrive at a comprehensive model of wound healing, one needs to integrate processes occurring on many different time and length scales." Despite the numerous existing mathematical models for both tumor growth and wound healing, the complexity of the biological processes continues to pose great challenges to mathematicians.

The last workshop of the year, on Drosophila development, will coincide with a historical event in the field: the 100th anniversary of the first use of Drosophila melanogaster as an experimental organism. "The identification of complete sets of genes responsible for a developmental process in general, and for Drosophila development in particular, provides an unprecedented opportunity to apply quantitative methods for a mechanistic understanding of complexity," says Michael Levine, an organizer of the workshop. The workshop will cover four broad topics that are particularly well suited for quantitative analysis: genome analysis, pattern formation of the early embryo and wing imaginal disc, computational modeling of signal transduction pathways, and the elucidation and analysis of gene-regulation networks.

"The year in developmental biology is intended to bring together mathematicians who have made significant contributions to basic processes involved in development with experimentalists working on specific systems for which a quantitative approach has been or may be productive," Friedman says. "We also hope to attract mathematicians who are looking to expand their research into the biological sciences."

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