Marie Skłodowska-Curie Postdoctoral Fellowship for Tzu-Jing Yang

Mechanistic understanding towards how progerin contributes to premature ageing

The Marie Skłodowska-Curie Actions of the European Union support the career of talented early career researchers who move abroad to gain experience in other countries and fosters excellence in science. Yang was among the 17.5 % of applicants who werer gruanted in 2023.

Objective:

The nuclear lamina is a meshwork of lamin proteins that underlie the inner nuclear membrane and confer mechanical stability to the nuclear envelope.
Mutations in lamins are associated with many disorders, including Progeria, a fatal premature ageing disease. In progeroid cells, expression of a
truncated form of lamin A, named progerin, drastically deforms the nuclear envelope, causing premature cellular senescence. However, the underlying
molecular mechanisms remain unclear.

Aim of the project, is the investigation of whether the NPCs indeed undergo compositional and conformational changes in Progeria patient-derived primary cells, and to what extent nuclear transport is impacted. To achieve this, in cellulo cryo-electron tomography will be applied to unveil the molecular organization of the progeroid NPCs. Fluorescence microscopy-based cellular assays will be further employed to identify proteins with nucleocytoplasmic mislocalization.

More