Universität zu Köln

Giorda, Marco ORCID: 0009-0008-7432-1348 (2026). C. elegans gene expression in metabolic homeostasis and ageing. PhD thesis, Universität zu Köln.

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Abstract

The maintenance of homeostasis requires coordination of gene expression across temporal scales, from responding to fluctuations in food availability to sustaining protein synthesis during ageing. Because of its distinct ecology and well-characterised ageing process, C. elegans serves as a powerful model to investigate such responses. I established two distinct research projects to explore these phenomena. In my first project, I asked whether food-deprived worms could use an olfactory food cue to initiate transcriptional responses preparing them for the arrival of nutrients. I discovered that fasting worms exposed to volatile diacetyl rapidly induce expression of gpdh-1 (glycerol-3-phosphate dehydrogenase) and other enzymes comprising the DHAP (dihydroxyacetone phosphate) shunt, a metabolic pathway repressed by food deprivation but induced during glucotoxicity and hyperosmotic stress. I demonstrated that this transcriptional response requires the MDT-15 (mediator subunit 15) transcription factor and drives rapid metabolic remodeling, characterised by the accumulation of glycerol and phosphatidylglycerols (PGs). If food remains absent, the metabolic activity of the DHAP shunt triggers a secondary gene expression response dominated by the dietary restriction (DR) marker fmo-2, promoting thermotolerance and food-seeking behaviours. These findings demonstrate that worms can indeed use an environmental food cue to preemptively rewire their gene expression and metabolic states in anticipation of nutrient arrival. In my second project, I investigated how C. elegans protein synthesis changes during ageing, specifically focusing on how the translational efficiency (TE) of individual genes and broader biological processes is affected. I found that while the majority of age-related changes in protein synthesis are dictated by underlying mRNA transcript abundance, a significant number of genes are altered at the translational level. I identified GC content and codon adaptation as potential intrinsic mRNA properties underlying these translational shifts. Most notably, the TE of genes involved in the translation process itself and in protein folding is particularly downregulated with age, which may contribute to the age-related decline in protein synthesis. Together, these projects illustrate the essential cross-talk across biological and temporal scales required to maintain homeostasis. By mapping the interplay of transcription, translation and metabolic adaptation, this thesis provides novel examples of how organisms dynamically orchestrate gene expression.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Giorda, Marco giorda.marco97@gmail.com https://orcid.org/0009-0008-7432-1348 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-812308
Date:	2026
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Außeruniversitäre Forschungseinrichtungen > MPI for Biology of Ageing
Subjects:	Life sciences
Uncontrolled Keywords:	Keywords Language metabolic homeostasis English translatome English gene expression English
Date of oral exam:	16 June 2026
Referee:	Name Academic Title Vilchez, David Prof. Dr.
Funders:	Max Planck Institute for Biology of Ageing, Altos Labs
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81230