NSF-BSF: Stress tolerance: Inheritance and regulation by diverse epigenetic mechanisms

This project seeks to determine how changes in the early-life (embryonic) environment cause lifelong effects on metabolism and stress responses that are passed on from parents to offspring in chickens. The epigenetic changes that are responsible for inheritance of physiological resilience in response to temperature stress will be studied in the blood and brain, and it will be determined how these changes are inherited and how they are regulated.

This work challenges the paradigm that epigenetic marks on the DNA are erased and reestablished at fertilization and suggests that environmental perturbations during critical stages of development can have lasting effects on the offspring and later generations. This research provides a framework for understanding the mechanisms involved in heritable behaviors that do not involve changes to the DNA nucleotide sequence.

The chicken is an ideal model for this research, because eggs can be incubated in large numbers under tightly controlled environmental conditions, and the lack of parental involvement eliminates potential confounding effects on development. The major theme of this research is physiological resilience, which parallels the theme of the broader impacts: professional resilience in a challenging environment.

The targeted outcomes are to enhance involvement of students from underrepresented groups in STEM research. The chick is an ideal research model to incorporate into the classroom because of the relative low cost and time investment for generating data and completing experiments. The collaboration between Virginia Tech and the Volcani Institute in Israel contributes to outcomes by demonstrating the importance of diversity and international cooperation in research.

The embryonic environment has long-term effects on physiological functions later in life. Embryonic heat conditioning induces lifelong (and transgenerational) heat resilience and cross-tolerance (i.e., improved health of other systems) within the immune and metabolic systems. Epigenetic marks are responsible for transgenerational transmission of stress responses, challenging the assumption that epigenetic modifications are erased in germ cells at fertilization.

Some of these changes are retained and passed down to subsequent generations. Epigenetic modifications will be followed in three generations of chickens, from in ovo (embryonic) heat conditioning, through life-long encounters with environmental challenges, insemination, primordial germ cells, and normal growth of two consecutive generations. Stress-, metabolic-, and inflammatory-related pathways will be studied in the blood and areas of the brain responsible for regulating such pathways, including the preoptic anterior hypothalamus and paraventricular nucleus of the hypothalamus.

Epigenetic mechanisms include DNA methylation and interactions with histone modifications, and epitranscriptomic marks, and these will be assessed using global (via sequencing) and loci-specific (through nucleic acid and protein interactions) methods. The work will be performed concurrently at Virginia Tech in the U.S.A. and the Volcani Institute in Israel, providing robust results with chickens from different genetic backgrounds in different geographical locations.

This project will be used as a platform to recruit students from underrepresented backgrounds into research, and will involve training for one graduate student researcher each year.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.