iGEM ProgERASE project: Evaluation of the efficacy of a RING-bait-like system in progerin degradation via SpyTag/SpyCatcher-induced interaction

Hutchinson-Gilford progeria syndrome is a rare genetic disorder with an incidence of approximately 1 in 20 million live births. In the majority of cases, it is caused by a de novo point mutation in the LMNA gene, leading to the production of a mutated form of lamin A protein known as progerin. The accumulation of progerin in the nucleus, together with its interaction with other components of the nuclear lamina, results in nuclear shape abnormalities, ultimately causing generalized premature aging of tissues and early mortality (around 14 years of age). The ProgeRING iGEM project aims to alleviate disease symptoms and slow down premature aging by promoting progerin degradation through the polyubiquitination activity of an engineered RING domain fused to a protein interactor designed using bioinformatic tools. This thesis focuses on validating the degradative activity of the RING-bait-like system through the expression of a RING-SpyCatcher and a progerin-SpyTag in mammalian cells.