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A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance

Mitochondrial energy metabolism plays an important role in the pathophysiology of insulin resistance. Recently, a missense N437S variant was identified in the MRPP3 gene, which encodes a mitochondrial RNA processing enzyme within the RNase P complex, with predicted impact on metabolism. We used CRISPR-Cas9 genome editing to introduce this variant into the mouse Mrpp3 gene and show that the variant causes insulin resistance on a high-fat diet.

Mitochondrial Medicine and Biology

Mitochondrial diseases are devastating disorders for which there are no cures or effective treatments. Our project will focus on the prevention of mitochondrial diseases and discovery of effective cures.

The mitochondrial single-stranded DNA binding protein is essential for initiation of mtDNA replication

We report a role for the mitochondrial single-stranded DNA binding protein (mtSSB) in regulating mitochondrial DNA (mtDNA) replication initiation in mammalian mitochondria. Transcription from the light-strand promoter (LSP) is required both for gene expression and for generating the RNA primers needed for initiation of mtDNA synthesis.

Stepwise maturation of the peptidyl transferase region of human mitoribosomes

Mitochondrial ribosomes are specialized for the synthesis of membrane proteins responsible for oxidative phosphorylation. Mammalian mitoribosomes have diverged considerably from the ancestral bacterial ribosomes and feature dramatically reduced ribosomal RNAs. The structural basis of the mammalian mitochondrial ribosome assembly is currently not well understood. Here we present eight distinct assembly intermediates of the human large mitoribosomal subunit involving seven assembly factors.

OmicsVolcano: software for intuitive visualization and interactive exploration of high-throughput biological data

Advances in omics technologies have generated exponentially larger volumes of biological data; however, their analyses and interpretation are limited to computationally proficient scientists. We created OmicsVolcano, an interactive open-source software tool to enable visualization and exploration of high-throughput biological data, while highlighting features of interest using a volcano plot interface. In contrast to existing tools, our software and user-interface design allow it to be used without requiring any programming skills to generate high-quality and presentation-ready images.

Developing new models of mitochondrial diseases using CRISPR/Cas technologies

Aleksandra Filipovska BSc PhD Louis Landau Chair in Child Health Research; NHMRC Leadership Fellow; Deputy Director, ARC Centre of Excellence for

Systems biology of mitochondrial diseases

Investigators: Professor Aleksandra Filipovska, Dr Stefan Siira Project description  This project will focus on new and cutting-edge development of

Estimating the potential malaria morbidity and mortality avertable by the US President's Malaria Initiative in 2025: a geospatial modelling analysis

Since its inception in 2005, the US President's Malaria Initiative (PMI) has played a major role in the reductions in malaria morbidity and mortality observed across Africa. With the status of PMI funding and operations currently uncertain, we aimed to quantify the impact that a fully functioning PMI would have on malaria cases and deaths in Africa during 2025. 

The Vsr-like protein FASTKD4 regulates the stability and polyadenylation of the MT-ND3 mRNA

Expression of the compact mitochondrial genome is regulated by nuclear encoded, mitochondrially localized RNA-binding proteins (RBPs). RBPs regulate the lifecycles of mitochondrial RNAs from transcription to degradation by mediating RNA processing, maturation, stability and translation. The Fas-activated serine/threonine kinase (FASTK) family of RBPs has been shown to regulate and fine-tune discrete aspects of mitochondrial gene expression.

Hyperactive Nickase Activity Improves Adenine Base Editing

Base editing technologies enable programmable single-nucleotide changes in target DNA without double-stranded DNA breaks. Adenine base editors (ABEs) allow precise conversion of adenine to guanine. However, limited availability of optimized deaminases as well as their variable efficiencies across different target sequences can limit the ability of ABEs to achieve effective adenine editing.