Overview

Endosomes have moved toward center stage, because of their role in immunity, development, signaling, adhesion, nutrient uptake, membrane turnover and defense against toxins and pathogens. Elucidating these fundamental cellular processes will require an understanding of the mechanisms that control endosome architecture and dynamics. Despite major progress over the last decade, the principles that guide the movement of proteins and lipids and the specific organization of endosomes — and compartments — are still poorly understood: how is the linear organization of the genome translated into 3D cellular architecture?

Research aims

Our work has uncovered some of the principles responsible for the biogenesis and dynamic properties of endosomal membranes, including specialized protein–lipid domains that are altered in human pathologies. We wish to understand the mechanisms that drive organelle biogenesis and maintenance — how organelle architecture controls functions — one of our main goals being to characterize the mechanisms that regulate the organization, dynamics and functions of endosomal membranes in human cells. We wish to further investigate the components, molecular assemblies and membrane domains that regulate intracellular membrane dynamics, and to investigate the principles that control the crosstalk between different mechanisms at the organellar level.

We are using in vitro assays that reconstitute each individual step of membrane transport along the endocytic pathway, so that these become amenable to biochemical manipulation in the test tube and precise quantification. These biochemical experiments are combined with in vivo studies and genetic manipulations using mostly tissue culture-cells, to gain mechanistic insights into the functions of key proteins and lipids. In parallel to such hypothesis-driven research, we are developing high throughput and systems-biology approaches to obtain a broader overview of the collective behavior of membrane components.