Search
Research
Multi-omic profiling reveals an RNA processing rheostat that predisposes to prostate cancerProstate cancer is the most commonly diagnosed malignancy and the third leading cause of cancer deaths. GWAS have identified variants associated with prostate cancer susceptibility; however, mechanistic and functional validation of these mutations is lacking.
Research
Copy number variation in tRNA isodecoder genes impairs mammalian development and balanced translationThe number of tRNA isodecoders has increased dramatically in mammals, but the specific molecular and physiological reasons for this expansion remain elusive. To address this fundamental question we used CRISPR editing to knockout the seven-membered phenylalanine tRNA gene family in mice, both individually and combinatorially.
Research
Frankenstein Cas9: engineering improved gene editing systemsThe discovery of CRISPR-Cas9 and its widespread use has revolutionised and propelled research in biological sciences.
Research
The mitophagy receptors BNIP3 and NIX mediate tight attachment and expansion of the isolation membrane to mitochondriaBNIP3 and NIX are the main receptors for mitophagy, but their mechanisms of action remain elusive. Here, we used correlative light EM (CLEM) and electron tomography to reveal the tight attachment of isolation membranes (IMs) to mitochondrial protrusions, often connected with ER via thin tubular and/or linear structures.
Research
TANGO2 binds crystallin alpha B and its loss causes desminopathyMutations in the TANGO2 gene cause an autosomal recessive disorder characterised by developmental delay, stress-induced episodic rhabdomyolysis, and cardiac arrhythmias along with severe metabolic crises. Although TANGO2 mutations result in a well characterised disease pathology, the function of TANGO2 is still unknown.
Research
Mitochondrial damage in muscle specific PolG mutant mice activates the integrated stress response and disrupts the mitochondrial folate cycleDuring mitochondrial damage, information is relayed between the mitochondria and nucleus to coordinate precise responses to preserve cellular health. One such pathway is the mitochondrial integrated stress response (mtISR), which is known to be activated by mitochondrial DNA (mtDNA) damage. However, the causal molecular signals responsible for activation of the mtISR remain mostly unknown.
Research
Control of mitophagy initiation and progression by the TBK1 adaptors NAP1 and SINTBADMitophagy preserves overall mitochondrial fitness by selectively targeting damaged mitochondria for degradation. The regulatory mechanisms that prevent PTEN-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase Parkin (PINK1/Parkin)-dependent mitophagy and other selective autophagy pathways from overreacting while ensuring swift progression once initiated are largely elusive.
Research
Unique architectural features of mammalian mitochondrial protein synthesisMitochondria rely on coordinated expression of their own mitochondrial DNA (mtDNA) with that of the nuclear genome for their biogenesis. The bacterial ancestry of mitochondria has given rise to unique and idiosyncratic features of the mtDNA and its expression machinery that can be specific to different organisms. In animals, the mitochondrial protein synthesis machinery has acquired many new components and mechanisms over evolution.
Research
Murine bone-derived mesenchymal stem cells undergo molecular changes after a single passage in cultureThe rarity of the mesenchymal stem cell (MSC) population poses a significant challenge for MSC research. Therefore, these cells are often expanded in vitro, prior to use. However, long-term culture has been shown to alter primary MSC properties.
Research
Illuminating mitochondrial translation through mouse modelsMitochondria are hubs of metabolic activity with a major role in ATP conversion by oxidative phosphorylation (OXPHOS). The mammalian mitochondrial genome encodes 11 mRNAs encoding 13 OXPHOS proteins along with 2 rRNAs and 22 tRNAs, that facilitate their translation on mitoribosomes.