Leptin Group

Cell shape and morphogenesis: subcellular and supracellular mechanisms

The Leptin group studies the mechanisms and forces that determine cell shape in Drosophila and uses zebrafish to analyse innate immune signalling.


Cell shape determination during development

The shape of a developing organism is generated by the activities of its constituent cells: growth and proliferation, movements, and shape changes. We are particularly interested in shape changes.

In one project we aim to understand how the forces generated by individual cells are integrated within the supracellular organisation of the whole organism to give the tissue its final shape. We study the formation of the ventral furrow in the early Drosophila embryo. The cells that form the furrow are the major force generators driving invagination, but to allow furrow formation, neighbouring cells must respond and they may contribute to the process. To understand force integration across many cell populations, we use live imaging, cell biology, and genetics. We measure the shape changes and mechanical properties in all the cells of the embryo. Genetic and mechanical manipulations reveal the underlying control circuits, and theory and simulations allow us to come up with explanations and formulate new hypotheses.

Another study concerns an extremely complex single cell, the terminal cell of the Drosophila tracheal system. It is highly branched and carries air to target tissues through an intracellular tube bounded by plasma membrane (Fig. 2). During its rapid growth, the cell faces the task of synthesising large amounts of membrane and sorting it correctly to defined membrane domains. Extensive reorganisation of the secretory organelles precedes membrane growth. We are investigating how the cytoskeleton, small GTPases, and polarity determinants direct the process, and how membrane trafficking processes contribute to building the tube.

In vivo imaging of innate immune responses

The innate immune system provides rapid defence against pathogens and also deals with non-pathogenic stresses. Macrophages and dendritic cells, two key players in this system, patrol the body and respond to stimuli from damaged cells via extra- and intracellular sensors. We aim to understand how such signals are recognised and how the appropriate subcellular and intercellular responses are triggered.

Fish model systems allow in vivo observation of physiological processes. Specifically, we watch pathogens and the cells that attack them. We use in vivo fluorescent reporters, such as the inflammasome component ASC (Fig. 3) to assay immune and stress responses in real time and at high spatial and temporal resolution as the cells of the fish encounter pathogens and stress signals.

Figure 3: Fluorescence micrograph of zebrafish skin in which the protein ASC (red) has formed inflammasome ‘specks’. ASC in the inflammasome kills cells (the one at the bottom has just rounded up and is dying), whereas diffusely distributed ASC does not.
Figure 1: Computer simulation of a network composed of flexible filaments, crosslinkers, and bivalent motors on the surface of a sphere. The elements form an initially homogeneously distributed meshwork that contracts over time.
Figure 2: Fluorescence micrograph of larval tissue with a tracheal cell (running across the bottom of the image) sending branches into a muscle (positioned diagonally from the bottom right to the middle).