Project Details

Description

Why complex life evolved on Earth has puzzled scientists for as long as sufficient oxygen has been deemed vital. Motivated by recent discoveries, however, we investigate the dawning paradox that multicellular life requires low oxygen (hypoxia) internally to thrive in the oxic niche. Mechanisms by which animals sense and maintain hypoxia are crucial for building tissue. For example, specific hypoxic tissue niches keep some cells protected from oxygen, which then supply new cells for repair and growth. From the fields of cancer and developmental biology, HIF-2α is known to induce cell stemness at physoxic conditions and thus contribute to the maintenance of stem cell pools. Since HIF-2α is unique to vertebrates, we thus ask if invertebrates (expressing HIF-1α only) have a weaker capacity for maintaining adult stem cell pools and thus for tissue renewal at oxic conditions.
High oxygen appears to shorten the life span of bees and flies. In fruit flies (Drosophila), death also relates to malfunctioning tissue renewal but it remains uncharacterized if their intestinal stem cells (ISC) are depleted as a function of exposure to oxygen. In this project, we explore the role of oxygen concentrations in animal tissues for tissue-renewal capacity in specifically invertebrates. Preliminary data obtained suggest that Drosophila stemness is reduced after 9 days at 40% O2 (as compared to at 10% and 21% O2). The flies are transgenic, such that stem cell protein in their ISC is fluorescent green (GFP) using the Gal4-UAS-driven expression. The experiments allow the monitoring ISC viability, using imaging (confocal microscopy) and sorting (FACS) of GFP positive cells, in combination with mRNA and cell differentiation markers. We will also carry out proteomic experiments to explore the mechanism by which oxygen may deplete the adult stem cell pool of fruit flies. The overall aim is to advance our understanding of whether exposure to oxygen of the adult depletes stemness capacity.
StatusActive
Effective start/end date2022/10/01 → …