**The AGA grants EECG Research Awards each year to graduate students and post-doctoral researchers who are at a critical point in their research, where additional funds would allow them to conclude their research project and prepare it for publication. EECG awardees also get the opportunity to hone their science communication and write posts over their grant tenure for the AGA Blog. In the first in the series, our EECG awardees write about their research and their interests as an ’embarkation’.**
About the Blog Author: Dr. Zachary Laubach is a National Science Foundation (NSF) Postdoctoral Research Fellow working with website: http://www.safran-lab.com/ at the University of Colorado, Boulder, and Dr. Kim Hoke at Colorado State University. He is a behavioral ecologist and evolutionary biologist interested in understanding how the type and timing of experiences contribute to the development of future phenotypes. Towards this end, he has studied diverse animals including hyenas, humans, and birds.
Early social experiences affect later life phenotypes through developmental plasticity, a process by which the same genotype produces distinct phenotypes in response to being reared in different environments. For example, over 20 years ago, Liu et al. demonstrated that less maternal licking and grooming during the first 10 postnatal days caused a blunted corticosterone response to a standardized stressor in adult rat offspring (Liu et al., 1997). This effect was subsequently shown to be independent of genetic differences via cross-fostering experiments (Francis et al., 1999). Similar findings have been reported in a wide variety of animals, thus supporting the notion that experiences early in life have profound and lasting impacts on an offspring’s phenotype. Yet, much remains unknown about the underlying mechanisms of this plasticity – an especially puzzling question given that long periods of time often separate the experience from the development of the phenotype. One proposed mechanism of developmental plasticity is DNA methylation, a well-characterized epigenetic mark that is responsive to environmental stimuli and regulates gene expression (Klose and Bird, 2006).
During my PhD, I tested hypotheses regarding molecular mechanisms and functional biomarkers through which early-life experiences affect physiology. In spotted hyenas, I found that early-life social and ecological factors affect patterns of DNA methylation assessed during multiple life stages. More specifically, I found that maternal social rank and ecological factors (i.e., anthropogenic disturbance, prey availability) prior to and during the first year of life are determinants of global DNA methylation in cubs (Laubach, Faulk, et al., 2019). I also detected a protective effect of social connectedness during the subadult life stage – a sensitive period in which young hyenas form their own affiliations, as opposed to relying on their mothers – on global DNA methylation and stress hormone levels. In addition, I conducted an epigenome-wide association study in hyenas and identified differential DNA methylation of genes that regulate inflammatory and aging pathways as intermediate biomarkers to the relationship between maternal care and adult stress physiology, pointing to inflammation as a determinant of health (Laubach et al., 2021). I also led a prospective analysis of maternal prenatal socioeconomic status (SES) and epigenome-wide DNA methylation in humans assessed from birth through early childhood. I found that lower prenatal SES corresponded with patterns of DNA methylation at birth, and limited evidence that patterns of DNA methylation persisted from birth to early childhood (Laubach, Perng, et al., 2019). Here DNA methylation occurred in regions of the genome involved in basic cellular processes implicated in the etiology of chronic diseases that disproportionately impact low SES populations. Collectively, findings from my previous work and the work of others implicate early developmental stages as key sensitive periods that influence future phenotypes and point to DNA methylation as a plausible mechanism of plasticity.
With support from the American Genetics Association, I plan to expand upon my previous work leveraging a long-term field study of wild N. American barn swallows (Hirundo rustica erythrogaster) that migrate each summer to established breeding sites in Boulder, Jefferson, and Weld counties, CO. Here, breeding sites are occupied by 1-50 breeding pairs. During each breeding attempt, pairs of swallows raise 3-6 offspring that both parents feed until fledging at ~18 days (Turner, 2010). Parental care is extensive, starting from the two-week incubation period which requires near constant parental presence at the nest, to the hatchling phase when parental care involves brooding followed by a transition to higher provisioning rates as nestlings grow and can thermoregulate (Brown and Browon, 2019). During the 2021 breeding season, a research team and I collected longitudinal data over the course of nestling development on parental care behaviors, nest microclimate, and nestling morphology. We also measured nestling physiology and collected blood samples for assessing patterns of DNA methylation. Using these data, I will test the hypothesis that experiences from hatching to fledging are associated with nestling growth and physiology, and that this relationship is mediated by DNA methylation. This work will enhance current knowledge of how and when various early life experiences affect phenotype development in a wild population.
Laubach ZM, Faulk CD, Dolinoy DC, Montrose L, Jones TR, Ray D, et al. (2019). Early life social and ecological determinants of global DNA methylation in wild spotted hyenas. Molecular Ecology 28: 3799–3812.
Laubach ZM, Perng W, Cardenas A, Rifas-shiman SL, Oken E, DeMeo D, et al. (2019). Socioeconomic status and DNA methylation from birth through mid-childhood: a prospective study in Project Viva. Epigenomics.
Laubach ZM, Greenberg JR, Turner JW, Montgomery TM, Pioon MO, Sawdy MA, et al. (2021). Early-life social experience affects offspring DNA methylation and later life stress phenotype. Nature Communications 12: 1–15.