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Université de Fribourg

Tissue-specific transcription footprinting using RNA PoI DamID (RAPID) in Caenorhabditis elegans

Gómez-Saldivar, Georgina ; Osuna-Luque, Jaime ; Semple, Jennifer I. ; Glauser, Dominique A. ; Jarriault, Sophie ; Meister, Peter

In: Genetics, 2020, vol. 216, no. 4, p. 931–945

Differential gene expression across cell types underlies development and cell physiology in multicellular organisms. Caenorhabditis elegans is a powerful, extensively used model to address these biological questions. A remaining bottleneck relates to the difficulty to obtain comprehensive tissue-specific gene transcription data, since available methods are still challenging to execute and/or...

Université de Fribourg

Retromer and TBC1D5 maintain late endosomal RAB7 domains to enable amino acid–induced mTORC1 signaling

Kvainickas, Arunas ; Nägele, Heike ; Qi, Wenjing ; Dokládal, Ladislav ; Jimenez-Orgaz, Ana ; Stehl, Luca ; Gangurde, Dipak ; Zhao, Qian ; Hu, Zehan ; Dengjel, Jörn ; Virgilio, Claudio De ; Baumeister, Ralf ; Steinberg, Florian

In: The Journal of Cell Biology, 2019, vol. 218, no. 9, p. 3019–3038

Retromer is an evolutionarily conserved multiprotein complex that orchestrates the endocytic recycling of integral membrane proteins. Here, we demonstrate that retromer is also required to maintain lysosomal amino acid signaling through mTORC1 across species. Without retromer, amino acids no longer stimulate mTORC1 translocation to the lysosomal membrane, which leads to a loss of mTORC1...

Université de Fribourg

Distinct genomic signals of lifespan and life history evolution in response to postponed reproduction and larval diet in Drosophila

Hoedjes, Katja M. ; van den Heuvel, Joost ; Kapun, Martin ; Keller, Laurent ; Flatt, Thomas ; Zwaan, Bas J.

In: Evolution Letters, 2019, p. -

Reproduction and diet are two major factors controlling the physiology of aging and life history, but how they interact to affect the evolution of longevity is unknown. Moreover, although studies of large‐effect mutants suggest an important role of nutrient sensing pathways in regulating aging, the genetic basis of evolutionary changes in lifespan remains poorly understood. To address these...

Université de Fribourg

Dietary restriction and other lifespan extending pathways converge at the activation of the downstream effector takeout.

Gáliková, Martina ; Flatt, Thomas

In: Aging, 2010, vol. 2, no. 7, p. 387-389

Dietary restriction (DR), reduced food uptake without malnutrition, is the most universal intervention known to extend animal lifespan, from invertebrates to mammals [1]. However, despite impressive progress in identifying the key components of the DR pathway, many proximal effectors of DR induced longevity remain unknown to date [1]. One central obstacle in the search for such mechanisms is...

Université de Fribourg

Diet and longevity in the balance

Flatt, Thomas

In: Nature, 2009, vol. 462, no. 24, p. 989-990

Dietary restriction promotes longevity but impairs fecundity in many organisms. When the amino acids in a diet are fine-tuned, however, lifespan can be increased without loss of fecundity — at least in fruitflies.

Université de Fribourg

Drosophila germ-line modulation of insulin signaling and lifespan

Flatt, Thomas ; Min, Kyung-Jin ; D'Alterio, Cecilia ; Villa-Cuesta, Eugenia ; Cumbers, John ; Lehmann, Ruth ; Jones, D. Leanne ; Tatar, Marc

In: Proceedings of the National Academy of Sciences of the United States of America, 2008, vol. 105, no. 17, p. 6368–6373

Ablation of germ-line precursor cells in Caenorhabditis elegans extends lifespan by activating DAF-16, a forkhead transcription factor (FOXO) repressed by insulin/insulin-like growth factor (IGF) signaling (IIS). Signals from the gonad might thus regulate whole-organism aging by modulating IIS. To date, the details of this systemic regulation of aging by the reproductive system are not...

Université de Fribourg

Reproduction, fat metabolism, and life span: what is the connection?

Hansen, Malene ; Flatt, Thomas ; Aguilaniu, Hugo

In: Cell Metabolism, 2013, vol. 17, no. 1, p. 10–19

Reduced reproduction is associated with increased fat storage and prolonged life span in multiple organisms, but the underlying regulatory mechanisms remain poorly understood. Recent studies in several species provide evidence that reproduction, fat metabolism, and longevity are directly coupled. For instance, germline removal in the nematode Caenorhabditis elegans promotes longevity in part...

Université de Fribourg

Life-history evolution and the polyphenic regulation of somatic maintenance and survival

Flatt, Thomas ; Amdam, Gro V. ; Kirkwood, Thomas B. L. ; Omholt, Stig W.

In: The Quarterly Review of Biology, 2013, vol. 88, no. 3, p. 185–218

Here we discuss life-history evolution from the perspective of adaptive phenotypic plasticity, with a focus on polyphenisms for somatic maintenance and survival. Polyphenisms are adaptive discrete alternative phenotypes that develop in response to changes in the environment. We suggest that dauer larval diapause and its associated adult phenotypes in the nematode (Caenorhabditis elegans),...