I find it exciting to examine apparently the simple mechanisms that regulate the transport of molecules between different organelles within cells that are essential for their integrity and correct functioning
Lysosomal storage disorders such as Niemann-Pick type C (NP-C) lead to the lysosomal accumulation of cholesterol and other lipids, resulting in malfunctions. This accumulation of cholesterol causes alterations in cell physiology, and these are responsible for the liver and neurodegenerative problems that affect patients with NP-C. Only by performing a detailed analysis of the molecular components and their interactions with lysosomes can the group stimulate alternative pathways to reduce surplus lipids and reactivate the lysosomal function.
Our knowledge of the proteomic repertoire of lysosomes has opened the door to the study of the interactions between the proteins involved in cholesterol transport and removal. The group is now studying the way in which the regulation, overexpression and silencing of determined proteins in this lysosomal environment affect the accumulated lipid levels and how to restore the cell function.
The most innovative strategy makes it possible to induce the formation of junctions between the lysosome membranes and other membranes of neighbouring compartments in order to promote molecular transfer.
The main objective is to restore the lysosomal and cellular function in vital organs such as the liver and brain in cell-based lysosomal storage disorder models. So far, the group has discovered a new pathway that enables the removal of cholesterol from the lysosomes that is independent of the most common transporter, the NPC1 protein (which is the cause of Niemann Pick type C disease).