The regulation of oxygen levels in animals is a crucial task. On one hand, oxygen is indispensable for aerobic life. However, either a shortage or excess of it can lead to dangerous conditions such as hypoxia (deprivation of oxygen in cells) or oxidative stress (inability to neutralize toxic reactive oxygen species in cells). These conditions may lead to the development of a variety of diseases, such as atherosclerosis (hardening of the arteries), Alzheimer’s and cancer. On the other hand, reactive oxygen species (ROS) plays an important role in fundamental processes in living animals. For example, they can act as second messengers in signal transduction pathways, used by phagocytes to protect against bacterial infection, and play a part in wound healing. Therefore, the double edges sword of oxygen metabolism poses a challenging task for living organisms.
In our lab, we are trying to understand how this fine balance of oxygen metabolism is maintained.
We use a hybrid approach that combines imaging techniques, biochemistry, genetics, and behavioral experiments to understand how:
1) Animals sense and respond to changes in oxygen concentration
2) Animals adapt to extreme oxygen levels
3) Neurons protect themselves against ROS
We use the nematode Caenorhabditis elegans as a model system. Thus, we are able to explore those questions at all levels, from the molecular to the organismal. Since most of the C. elegans genes have human homologs we hope that our studies will help to understand the fine balance of oxygen metabolism in humans cells as well.
To explore oxygen responses in vivo, we use genetically encoded calcium sensors that can be express in specific neurons or any other tissue in C. elegans. For example, in the movie above (left panel) we monitored the calcium responses of a single neuron (URX) in the C. elegans brain in response to a 21 7 21 oxygen concentration transition. In the right panel, we see the quantification of the calcium changes in the URX neuron.