Principal Investigator, Director of MPI for Biology of Ageing
Prof. Dr. Adam Antebi
Prof. Dr. Adam Antebi’s research group focuses on how evolutionarily conserved signal transduction pathways, hormonal mechanisms, and metabolism impact development and longevity in the nematode Caenorhabditis elegans. Such new insights into mechanisms that regulate lifespan may lead to innovative approaches to improve human health into old age.
Our research: Prof. Adam Antebi and his research team focus on the effects of the endocrine system and metabolism on development and life span. Using the nematode C. elegans as a model organism, they unravel the molecular mechanisms of how dietary restriction extends health and life span. They also investigate how hormonal signals from the reproductive system alter animal development and longevity. Finally they explore how metabolism and quality control mechanisms impact maintenance of cellular organelles and organismal survival. From a molecular perspective they examine the influence of steroids, insulins and micro-RNAs on animal longevity. Additionally they explore how activation of the hexosamine pathway and other metabolic pathways stimulate protein quality control, which protects cells within the organism from age-related proteotoxicity and neurodegeneration.
Our successes: Early work from Prof. Antebi‘s research group demonstrated that a steroid receptor in C. elegans regulates longevity in response to signals from the reproductive system. They further showed that these pathways also affect the organism´s developmental progression through its 4 larval stages, thus having broad spectrum effects on temporal control at all life phases. The signaling and metabolic inputs onto steroid receptor signaling and their downstream outputs are of great future interest. Furthermore, Dr. Antebi and his team discovered a critical link between steroid receptors and the FOXO transcription factor via let-7 microRNAs, revealing important crosstalk between these longevity factors. Most recently Prof. Antebi and his group have shown that activation of hexosamine metabolism and increased cellular concentration of the hexosamine metabolite N-acetylglucosamine enhances protein quality control. This increases lifespan and eliminates damaging protein aggregates that can act as triggers for neurodegenerative diseases.
Our goals: Future research in the Antebi laboratory will continue to have a focus on unraveling hormonal signaling pathways and downstream mechanisms that improve protein quality control, immunity, and metabolism. Moreover, Prof. Antebi and his team of scientists hope to manipulate the hexosamine pathway in order to stimulate protein quality control mechanisms and attenuate neurodegenerative diseases. If this should prove to be the case, their findings might provide a novel therapeutic approach for many neurodegenerative and aging-associated diseases.
Our methods/techniques: Prof. Antebi’s laboratory uses genetics combined with biochemical, cell biological, microscopic, and demographic methods to reveal the functions of genes/pathways of their interest and their effects on lifespan. Additionally the scientists employ a systems biology approaches to uncover the global network of changes in the transcriptome and proteome.
Figure 1: BLMP-1 regulates maturational events in various tissues. BLMP-1::GFP levels peak when epidermal stem cells, called seams, fuse together during a terminal differentiation event. DRE-1/FBXO11 is involved in degrading BLMP-1; upon dre-1/FBXO11 depletion, BLMP-1::GFP is elevated earlier in larval development. DIC and BLMP-1::GFP images of young wt L4 larvae.
Figure 2: Wild-type and gfat-1 gain-of-function mutants carrying a marker of ER stress, hsp-4::gfp, were exposed to tunicamycin. Supplementation with UDP-N-acetylglucosamine or presence of the gfat-1 gain-of-function alleles dh468, dh784, and dh785 significantly suppressed hsp-4::gfp induction (green fluorescence) because they neutralize ER stress induced by tunicamycin challenge.
Figure 3: Microscopic picture of Caenorhabditis elegans worm: Blue fluorescence marks the tissues expressing the enzyme GFAT, which is involved in the production of UDP-N-acetylglucosamine, a metabolite of the hexosamine pathway that can prevent toxic protein aggregation.