In our lab, we are interested in interorganellar contact sites, their mechanism of action and their implications in ageing and human diseases such as neurodegeneration and cancer. We also aim to elucidate the composition of these structures under healthy and pathological conditions and to directly target and modulate these structures with potential therapeutic implications. We are particularly interested in mitochondria- endoplasmic reticulum contact sites (MERCS) that are involved in mitochondria-ER communication and associated cellular functions. As their study has been challenging due to their dynamic and heterogeneous nature, we have developed several techniques that enable us to tackle these dynamics structures under different physiologically relevant conditions and in various cellular systems. These include, amongst others, a novel home-made BRET-based biosensor that enables the analysis of mitochondria-ER distance in living cells without perturbing their canonical disposition. Moreover, considering the intimate contact between the mitochondria and ER during mitochondrial apoptosis, we also focus on the regulatory role of MERCS in BCL-2-mediated sublethal apoptosis and inflammation signalling.
MERLIN, a novel BRET based biosensor for MERCS assessment in different cellular systems (immortalized cells, neuroprogenitors and mature neurones). Proximity-dependent biotin labelling coupled to mass spectrometry (MS) optimized for MERCS characterization. Microscopy: confocal, STED, EM. Cell death assays (caspase activation, inflammation signalling, in vitro reconstitution systems like model membranes or isolated mitochondria, and others).
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