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  • scheme1
    One of the major research directions is related to the quantitative analysis of
    enzyme kinetics in cells and tissues. We chose the highly conserved Extracellular
    Signal Regulated Kinase (ERK) as a model enzyme and explore its regulation and
    function at multiple levels of organization from the 3D structure of the ERK protein
    to the multicellular patterns of ERK signaling in embryos. Here is an example of one
    of the projects in this area: ERK interacts with its regulators and substrates via two
    localized regions on the surface of the ERK structure, known as docking domains.
    We are characterizing the effects of these docking domains on the rates of enzymatic
    reactions involving ERK. Read more
  • ras2
    Side by side with working on the mechanisms of ERK regulation in vitro, we are studying the spatiotemporal patterns of ERK activation in
    vivo
    focusing on developing tissues. These patterns are established by the localized activation of cell surface receptors and play key roles
    in controlling gene expression in embryos. Studies in multiple experimental systems suggest that quantitative changes in the duration or
    strength of ERK activation can lead to a range of developmental abnormalities, from heart defects, to short stature, and craniofacial mal-
    formations. It appears that both reduced and excessive ERK signaling can lead to problems in development. So what is the normal range
    of ERK activation? Surprisingly, the answer to this question is largely unknown. Read more
  • slide4
    Our recent work provided the first high-resolution view of ERK activation in a developing tissue. Using high-throughput
    imaging of Drosophila embryos, we reconstructed ERK activation with the spatial resolution of a single cell and temporal
    resolution of just a couple of minutes. At this stage of embryogenesis, locally activated ERK (red) triggers the expression
    of ind (cyan), a gene involved in patterning of the nervous system. Read more
  • plots
    Dynamics of gene induction in a developing tissue: a pulse in the production of an extracellular ligand (green) triggers
    a pulse in the activation of an intracellular enzyme (red), which in turn induces a target gene (blue). The inductive signal
    appears to work as a switch: The gene is induced to its maximal level once ERK activation crosses a certain threshold. We
    are testing this model by analyzing gene expression induced by signals with tailored durations and strengths. Read more
  • appendages
    We are developing computational models of shape transformations
    during epithelial morphogenesis, a set of processes which convert two
    dimensional sheets of cells into three dimensional structures. Our work
    on epithelial morphogenesis grew out of studies of pattern formation in
    the developing Drosophila egg. In this system, an epithelial sheet
    that envelops the growing oocyte gives rise to the three-dimensional
    structures of the eggshell, including the respiratory appendages. Each of
    the appendages is derived from a flat primordium which is established
    by the localized activation of the ERK pathway, which establishes precise
    patterns of gene expression and guides a morphogenesis that proceeds
    through a sequence of ordered cell rearrangements. Read more
  • miriam-e1434325803468
    Some of the key aspects of Drosophila eggshell
    morphogenesis can be captured by a computational
    model based on the vertex description of epithelial
    dynamics. Using the model, we could investigate which
    features of two-dimensional patterns of cell properties
    that can lead to a target three-dimensional structure.
    Current work explores applications of vertex models to
    other biological systems, including early stages heart
    development in zebrafish. Read more
  • Morphogen
    Morphogen gradients are concentration profiles of
    molecules that act as dose-dependent regulators of
    cell differentiation in developing tissues. Over the
    years, we have worked on experimental approaches
    for high-throughput analysis of morphogen gradients
    in multiple developmental contexts, derived analytical
    results related to the dynamics of morphogen gradient
    formation, and elucidated several mechanisms responsible
    for their transcriptional interpretation. Read more
  • During Drosophila embryogenesis, the fertilized egg gives rise to larva, a system with multiple cell types, tissues and organs.
    Only oxygen enters the system during this process, which is fuelled by maternally supplied stores of energy-rich molecules.
    We are probing the dynamics and regulation of energy utilization during embryogenesis, which can be contrasted with a
    burning candle, when all of the energy stored in the fuel is lost to the environment. Read more
  • yohesh_web
    The growing Drosophila egg chamber is a cluster of 15 nurse cells and a
    single oocyte. During oogenesis, the volumes of these cells increase by
    almost three orders of magnitude. This experimental system provides a
    platform for answering many important questions in cell regulation. For
    instance, how do the sizes and the numbers of organelles adjust to cell
    size? We are trying to answer this question for mitochondria, which are
    thought to be active in nurse cells and less so in the oocyte. Read more
Researchjasmin2019-11-06T20:55:12+00:00
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