A/Prof. Diana Stojanovski 
The University of Melbourne, Australia

Molecular mechanisms underscoring Citrin biogenesis and dissecting compensatory pathways in CD using CRISPR screens

This project builds on prior discoveries on the Citrin protein by the Stojanovski lab, focusing on its biogenesis and potential therapeutic strategies for Citrin Deficiency (CD). Using cell lines with SLC25A13 knocked out, the team previously identified key regions of Citrin responsible for mitochondrial targeting and demonstrated successful delivery and stability of Citrin via mRNA-LNP technology. The current work expands on these findings by dissecting the role of Citrin’s regulatory domain in its integration into the mitochondrial inner membrane, and applying CRISPR-based functional genomics screens (CRISPRa and CRISPRi) to identify genes that modulate survival and metabolic function in Citrin-deficient cells. Top candidates will be validated, with the goal of uncovering novel regulatory mechanisms and therapeutic targets for CD.

(Updated October 2025)