Rescue of defective lipid handling in Cohen syndrome
Awardee: Jens Luders
Institution: Institute for Research in Biomedicine (IRB Barcelona), Spain
Grant Amount: $83,282.00
Funding Period: February 1, 2024 - January 31, 2025
Summary:
The molecular function of VPS13B, the gene that is mutated in Cohen syndrome, is still poorly understood. Our previous work suggested that mutation of VPS13B reduces the amount of certain types of fat molecules in patient cells. Since these fat molecules are essential for the structure and function of cells and for the formation of tissues and organs during development, a reduced amount of these fat molecules may cause the clinical features observed in Cohen syndrome patients. In this project we will test which aspect of the handling of these fat molecules – uptake, transport, or storage – is defective in cells of Cohen syndrome patients. We will then try to repair the defect by introducing variants of intact VPS13B into these cells. Since VPS13B is very large, we will also test smaller versions, which are easier to work with. We will then also try to repair the loss of VPS13B in two additional models, retinal tissue grown in a culture dish that is derived from patient cells, and zebrafish embryos that lack VPS13B, which recapitulate several Cohen syndrome features including brain and eye defects. The project aims to identify VPS13B variants that can be used to provide the crucial functions of VPS13B in cells that lack VSP13B. The results may be useful for developing gene therapy in the future.