Understanding Life in Homeostasis and at Extremes

 

As humans, we drink when thirsty, eat when hungry, and increase our breathing and heart rates when short of oxygen. How do we (our bodies) know when and how to respond to changes in internal bodily states (e.g. loss of nutrient or oxygen)? Genes and traits that facilitate such underlying mechanisms confer great advantages for animal survival and are strongly selected for during evolution. We study how animals sense and respond to changes in internal states to elicit behavior and maintain homeostasis. Dysfunction of these fundamental life processes leads to many disorders, including metabolic, neurological and cardiovascular diseases. We use C. elegans and large-scale genetic screens as discovery tools to identify novel gene/pathway/cellular functions followed by validation of conserved principles in other systems.

 

Unlike humans, many organisms in nature survive or even thrive under extreme conditions. For example, C. elegans can be frozen, thawed alive and survive anoxia while certain Antarctic nematodes survive natural freezing. We investigate how nematodes adapt to and tolerate extreme conditions by entering an ametabolic state of life (cryptobiosis). This will help uncover novel mechanisms of extreme physiology, with potential applications in organ transplantation, reversible cryo-preservation and ischemic disorders.

 

Near-term specific projects include:

 

Discovering novel conserved mechanisms for animal response to hypoxia and reoxygenation

 

Genetic screens for novel interoceptive receptors

 

Mammalian (mouse and ground squirrel stem cell) models to understand mechanisms of innate tolerance to ischemia-reperfusion injury

 

For the long term, we explore non-conventional models, including mangrove killifish, the “hermaphrodite vertebrate counterpart of C. elegans” that tolerates hypoxia, and develop genetic approaches to study extreme physiology and understand how the brain interacts with circulatory/respiratory systems to coordinate internal homeostasis and tolerance of harsh environmental stimuli.

 

Our lab at UCSF started in Jan 2015. Please contact us with CV for research positions.