Phosphate homeostasis and energy metabolism (read more here)
My interest for phosphate homeostasis and the function of highly phosphorylated molecules (inositol polyphosphate and inorganic polyphosphate) started during my first postdoc when I was working on membrane trafficking at the University of Lausanne (Switzerland)(see below). I then decided to move to a lab with theoretical and experimental expertise in phosphate homeostasis and energy metabolism. I am now working in the lab of Adolfo Saiardi at the University College London (MRC LMCB).
My research brings together metabolism and signaling and focuses on how eukaryotic cells sense intracellular phosphate, how they deal with phosphate stores, and how they regulate the size of the different phosphate pools (inositol polyphosphate, inorganic polyphosphate, nucleotides pool, free phosphate). I am using two model systems to tackle the problem: yeast (Saccharomyces cerevisiae, Schizosaccharomyces pombe) and the social amoeba Dictyostelium discoideum.
Membrane trafficking/homeostasis (read more here)
Cells are well organized units which contain dozens to hundreds of compartments of specialized functions. Segregation of function is made possible by the existence of membrane bilayers that define clear separate compartments. It also comes from the formation of microcompartments within membranes, or within the cytosol/lumen of organelles (such as hydrogels, macromolecular complexes…). The different compartments are dynamic and communicate with each other via non-vesicular and/or vesicular exchange of materials. Vesicular exchange means that vesicles are formed from one compartment, are transported over long distances, and finally fuse with a target compartment. Examples of such events are represented on the figure below.
I am currently working on membrane fusion and polyphosphate/phosphate homeostasis. Membrane fusion is needed for lipid and protein trafficking. This mechanism can be studied in vivo and in vitro using vacuoles (yeast lysosome-like organelles). In yeast, the protein complex responsible for polyphosphate synthesis is absolutely required for homotypic vacuole fusion. Moreover, a large number of proteins involved in phosphate homeostasis are needed for the cells to keep a normal vacuole morphology. What is the relationship between polyphosphate/phosphate and membrane fusion?
Vacuole dynamics can be seen in vivo after labeling the organelles with the fluorescent dye FM4-64. Cells were attached in a microfluidic chamber and continuously washed with fresh medium during around 20 min (1 picture/min).
The molecular machinery required for fusion has been well described. However, how the full reaction is regulated is less well understood. Are there different checkpoints that should be reached before full fusion is achieved? What are the different steps that are actually controlled by the cells? Is SNARE activation (cis-SNARE disruption) by NSF/Sec18 a key regulatory step?