Current Projects

Stem Cell Aging

Adult (somatic) stem cells play a crucial role in maintaining and regenerating our organs. However, their function and number decrease during aging (Ermolaeva et al., Nat Rev Mol Cell Bio 2018). A particular focus of the group is to understand molecular mechanisms that lead to the loss of regenerative capacity of adult stem cells. Focusing on different organs, the group employs state-of-the-art mass spectrometry based proteomics to obtain proteome profiles of stem cells and the surrounding tissue (stem cell niche) across age groups and genetic backgrounds, as well as to evaluate the consequences of environmental factors such as stress, calorie restriction and exercise.

We have previously shown that multiple mechanisms can influence the availability of functional proteins during aging. These include changes in protein synthesis, intra-cellular localization and post-translational modifications (Cellerino and Ori, Sem Cell Dev Biol 2017). Currently, we apply and develop novel approaches that use mass spectrometry to study protein interactions (Mackmull et al., MSB 2017), stability, organelle composition (Wyantt et al., Science 2018; Parca et al., MSB 2018) and different types of post-translation modification in the context of aging. Current major focuses are the protein-protein interactions in the proteostasis network and non-enzymatic post-translational modifications such as Advanced Glycation End products (AGEs).

By taking advantage of the natural variability in lifespan between species, we aim to identify key determinants of longevity, and bring these in the context of human aging (Heinze, et al., BMC Biology 2018). Thanks to internal (Cellerino group) and external collaborations (Thomas Hildebrandt, IZW, Berlin), we have access to multiple model organisms ranging from the short-lived fish Nothobranchius furzeri, which has a lifespan of approx. 40 weeks, to the long lived rodent naked-mole rat that can live up to 30 years. The majority of our studies are based on unbiased integrated omics approaches, bioinformatic analysis, and follow up studies in established model organisms of aging.

References:

2018

Ermolaeva et al. (2018). Cellular and epigenetic drivers of stem cell ageing.
Nat Rev Mol Cell Biol, 19(9), 594-610. [PubMed]

Heinze et al. (2018). Species comparison of liver proteomes reveals links to naked mole-rat longevity and human aging. BMC Biol 2018, 16(1), 82. [PubMed]

Parca et al. (2018). Quantifying compartment-associated variations of protein abundance in proteomics data. Mol Syst Biol, 14(7), e8131. [PubMed]

Wyant et al. (2018). NUFIP1 is a ribosome receptor for starvation-induced ribophagy. Science, 360(6390), 751-8 [PubMed]

2017

Cellerino & Ori (2017). What have we learned on aging from omics studies? Semin Cell Dev Biol, 70, 177-89. [PubMed]

Mackmull et al. (2017) Landscape of nuclear transport receptor cargo specificity. Mol Syst Biol 2017, 13(12), 962. [PubMed] Highlighted in the “Principle of Systems Biology” - Cell Systems 6 - 2018