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

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

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

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

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

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