Mission statement:
Our group investigates cellular rescue pathways to mitochondrial dysfunction to devise novel therapeutic strategies for mitochondrial and related disorders.
Genome-wide screening for suppressors of mitochondrial dysfunction

We use genome-wide screening methods to identify suppressors of mitochondrial dysfunction to identify therapeutic targets for primary and mitochondria-associated diseases.

Mitochondrial protein synthesis

The essential orchestration of nuclear and mitochondrial proteins synthesis to generate equimolar amounts of respiratory chain complexes encoded by two genomes suggest a higher order of regulation.

This projects aims to understand how mitochondrial translation is regulated upon mito-nuclear imbalance.

The mitochondrial ribosome

Mitochondrial ribosomes (mitoribosomes) have undergone substantial structural remodelling throughout evolution. Compared to their prokaryotic counterparts, mitoribosomes show a substantial loss of ribosomal RNA, whilst acquiring unique protein subunits located on the periphery of the ribosomal subunit structures. 

Mitochondrial signalling

Mitochondria are an ancestral endosymbiont with a small remnant of actively replicating DNA encoding essential genes for oxidative phosphorylation. Dependent on the cellular need and cell identity, this organelle drives diverse metabolic reactions including amino acid, nucleotide and lipid synthesis.

We investigate limiting metabolites for these reactions and the regulation of retrograde signalling pathways between the mitochondria and nucleus triggered by organelle dysfunction. These mechanisms have a direct role in the molecular pathogenesis of human disease and are associated with a broad spectrum of human pathology including neurodegenerative, cardiovascular and metabolic diseases, as well as cancer and ageing. 

Understanding the molecular and metabolic events, governing these organelle-driven pathways and resulting elicited signalling responses induced by mitochondrial dysfunction, therefore is key in developing of potential therapeutic interventions. 

Mitochondrial retrograde signalling responses

Upon dysfunction, the mitochondria signal to the nucleus to alter and adapt nuclear gene expression, thereby eliciting specific transcriptional stress responses.

This projects aims to understand how these signals are transmitted to the nucleus and the subsequent programs initiated.