During the aging process, different stress response pathways, such as the unfolded protein response (UPR), the mitochondrial stress response (MSR), and the DDR – as studied in RA-1 – are tightly coordinated, thereby ensuring physiological integrity especially upon metabolic changes. Notably, different tissues have differing metabolic profiles that confer different responses when disturbances of these pathways occur. Beyond the cell autonomous control of these critical aging-regulating pathways, recent studies have identified cell non-autonomous regulation of cellular stress responses, suggesting interorgan communication mechanisms that are intricately balanced for integration and maintenance of the entire organism. Moreover, to date, most studies have mainly addressed individual stress response pathways, rather than examined their systemic coordination in specific cell types or between different organs. Thus, RA-2 aims to unravel the interplay between homeostasis pathways at the molecular, cellular, and organismal level as well as to define adaptation mechanisms in response to aging or inherited, disease-associated mutations. The key objectives of RA-2 are to investigate:
Figure 1: Interorgan communication
Figure 2: Epithelial wound in the Drosophila larval epidermis. One cell has been killed by laser. The neighbouring cells expand their apical membranes (black: PIP3-sensor) and form a contracting actin cable around the wound area (red).
Figure 3: mTORC1 and mTORC2 are activated during epidermal embryogenesis in mice and epidermal mTOR deficiency (mTOR-EKO) attenuates downstream signalling and epidermal barrier development and skin function (Ding et al., Nat Commun 2016)
Figure 4: C. elegans’ sense of smell depends on olfactory neurons (red); loss of function in odor perception results in deteriorations of the intestinal recycling system, visualized by the accumulation of green fluorescent protein (GFP).