KILLIFISH EMBRYONIC DIAPAUSE II

In a natural environment many organisms enter into a metabolic arrest in response to environmental changes or stress. Fascinating examples of metabolic/developmental arrests include torpor, diapause and hibernation. We are using the killifish embryo as a model to better characterize embryonic diapause at a cellular and genetic level. A comparison between anoxia induced suspended animation and embryonic diapause will allow us to identify conserved and unique processes for each state.

Padilla Lab Research

RESEARCH THEME: HYPOMETABOLISM, ENVIRONMENT, GENOTYPE, DEVELOPMENT AND STRESS

Genetic model systems have been fundamental for understanding mechanisms regulating biological processes and furthering our understanding of cellular functions that affect human diseases.  We are interested in understanding the interplay between environments (oxygen deprivation, diet), genotype, developmental trajectory and survival and response to stress.  This research is supported by the National Science Foundation.

LONG-TERM ANOXIA SURVIVAL
C. elegans frequently encounters oxygen-deprived microenvironments in its natural habitat thus the species has adapted to tolerate this stress. Wild-type adult C. elegans survive one day of anoxia however the viability drastically decreases and cellular injury increases in longer exposures to anoxia (3 days). The adult anoxia-tolerance strategies include the worm entering a reversible state of suspended animation.  In this state adults do not feed, do not lay eggs and cease to be motile. We have conducted genetic analysis to identify genotypes that enhance anoxia survival. This work will help identify molecular changes that enhance oxygen deprivation survival.

GERMLINE FUNCTION AND OXYGEN DEPRIVATION
We determined that germ line function affects how the adult organism responds to and survives oxygen deprivation. For example, a mutation in the glp-1 gene (encodes an N-glycosylated transmembrane receptor that is one of two members of the LIN-12/Notch family of receptors) significantly enhances anoxia survival. Genetic analysis is being conducted to further understand signaling pathways between stress survival and germline function.

ANOXIA-INDUCED SUSPENDED ANIMATION IN THE EMBRYO

There are known environmental changes that influence cell cycle progression (EX: UV radiation, Oxygen levels). Anoxia-exposed C. elegans embryos contain blastomeres that arrest at specific positions of the cell cycle: interphase, late prophase and metaphase.  A hallmark of an anoxia-arrested prophase blastomere is that the condensed chromosomes associate with the inner nuclear periphery; we refer to this phenotype as “chromosome docking”. The phenomenon of anoxia-induced arrest is not unique to C. elegans since zebrafish (Danio rerio) and Drosophila melanogaster embryos also arrest cell cycle progression in response to anoxia or hypoxia. Genetic and cellular analysis has been instrumental in identifying processes that are likely involved in anoxia-induced suspended animation in C. elegans. The Padilla lab is interested in identifying the signaling pathway between low oxygen and reversible cell cycle arrest in the C. elegans embryo.

HYPOXIA AND DEVELOPMENT

The response C. elegans has to oxygen deprivation depends upon the level of oxygen within the environment. That is, in very extreme levels of oxygen deprivation (anoxia) the animals will arrest energy requiring processes. In low levels of environmental oxygen the developmental trajectory will be slowed and various behavior changes are observed. We are interested in further characterizing hypoxic responses and identifying the mechanisms involved with slowing of developmental trajectory and behavioral changes in response to hypoxia.

AGING AND STRESS

Many labs have uncovered genetic processes involved with aging. We are interested in further understanding the relationship between stress responses and longevity. Interestingly, several of the genetic pathways or physiological changes involved with longevity (EX: insulin-signaling or reproduction) also have a role in stress responses. We are using genetic and physiological techniques to further understand overlapping and distinct genetic pathways between aging and stress. Furthermore, we would like to determine, at a molecular level, how stress influences the aging processes.

DIET, INSULIN-LIKE SIGNALING AND OXYGEN DEPRIVATION

Diet has an enormous impact on biological processes within living organisms.  We are studying metabolic and stress responses at the genetic and cellular level.  There are many signaling pathways that are involved with this complex process.  For example, the insulin-like signaling pathway is central to various biological processes.  Instrumental work by others has shown that the DAF-2 receptor and the signal cascade targeting the transcription factor DAF-16 has a central role in dauer formation, aging and stress resistance.  We are examining the role the DAF-2/DAF-16 signaling pathway has in anoxia survival.  Furthermore, we are interested in studying stress resistance in relation to diet, and the aging process.  This work is relevant to many human health related issues including diabetes.