Research

We investigate the role of evolutionarily conserved cellular factors and mechanisms regulating gene expression at the post-transcriptional or post-translational level, in the ageing process and the general stress response in the nematode Caenorhabditis elegans. This research will provide important knowledge regarding normal ageing and unveil potential approaches for delaying or preventing age-related diseases.

Specific ongoing research projects

1. Cytoplasmic mRNA metabolism factors and related RNA particles in ageing and stress
2. GCN-2 kinase in Dietary Restriction response
3. LON proteases in physiological processes of C. elegans

Facilities

1) Specific ongoing research projects

Cytoplasmic mRNA metabolism factors and related RNA particles in ageing and stress

Control of mRNA turnover is essential for all eukaryotic cells in order to maintain mRNA and protein homeostasis by removing transcripts that are no longer needed, or aberrant mRNAs that could potentially produce toxic proteins. The fate of mRNAs in the cytoplasm is determined by their association with various RNA-binding proteins, which can promote either degradation of mRNAs or their translational silencing and storage until developmental or environmental cues require their translation. This regulation of mRNA turnover/storage can take place at specific cytoplasmic RNA granules, such as mRNA processing bodies (P-bodies or PBs) and stress granules (SGs). We use fluorescent markers for these RNA granules to characterize the age-related pattern changes in somatic cells of adult worms and their physical interaction. We also analyze the effects of direct alterations in their function (by mutations, RNAi-mediated depletion or overexpression), in physiology, lifespan and stress response in worms.

GCN-2 kinase in Dietary Restriction response

Dietary restriction (DR), the reduction of food intake without malnutrition, can extend lifespan in various organisms and ameliorate ageing-related disability and pathology. Research on underlying mechanisms of DR response has implicated major nutrient-sensing pathways, such as Insulin/IGF-1 and TOR kinase signaling. Down-regulation of their activity extends lifespan possibly through reduction of anabolic processes (e.g. protein synthesis) and induction of catabolic processes (e.g. autophagy). GCN2 kinase is a conserved eIF2α kinase that responds to amino acid deprivation and contributes to reduction of global protein synthesis with a simultaneous selective translation of specific, stress-responsive mRNAs. We are studying the impact of GCN-2 signaling in DR-mediated longevity and stress response in worms. Also, the interplay between GCN-2 and known DR regulators is investigated.

LON proteases in physiological processes of C. elegans

The evolutionarily conserved AAA+ LON proteases are key players of both mitochondrial and peroxisomal proteolytic systems, with their primary function being prevention of aggregation of unfolded, misfolded or damaged proteins in the matrix of the corresponding organelles. They can also participate in a wide range of regulatory cellular processes, having a broad role in the maintenance of protein homeostasis under both normal and stress conditions. However, little is known about their function or their interaction with known longevity and stress signaling pathways in C. elegans. We seek to understand how these proteases affect the physiological processes of worms and uncover possible relative cross-talk between them and the protective mechanisms/pathways of protein homeostasis and longevity.

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2) Facilities

• Worm transgenesis unit (microinjection system)
• Fluorescent dissecting stereoscope
• RT-qPCR instrument

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