NSF Postdoctoral Fellowship in Biology FY 2021: Resolving the evolution of stress axis signaling in vertebrates

Shaughnessy, Ciaran A, Denver CO

Investigators

Abstract

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2021, Integrative Research Investigating the Rules of Life Governing Interactions Between Genomes, Environment and Phenotypes. The fellowship supports research and training of the Fellow that will contribute to the area of Rules of Life in innovative ways. In response to environmental stress, vertebrate animals exhibit a classically described ‘fight or flight’ physiological response, a highly conserved and essential survival instinct. During stress, a signaling pathway between the brain and other organs upregulates production of steroid hormones that prime the stressed body for ‘fight’ or ‘flight’ action. How this complex and essential endocrine system evolved in the earliest forms of vertebrate life has remained a mystery. The overarching scientific goal of this research is to combine the use of newly available genomic resources for basal vertebrates (i.e., hagfish and lamprey) with classical and cutting-edge in vivo and in vitro experimentation to mechanistically explain the evolution of this complex endocrine network. Research during this fellowship would establish new collaborations between categorically different institutions in the USA and abroad. The Fellow will spearhead efforts to promote senior-level near-peer mentorship to students in STEM and engage with established programs at the University of Denver that aim to increase the participation, enrollment, and success of under-represented students in STEM. This research will be combine in vivo studies on the stress response in basal vertebrates with in vitro studies on the molecular relationships between hormones and their receptors. In vivo studies in hagfish and lamprey will identify the neuroendocrine hormones (i.e., melanocortins) that are released from the brain and the corticosteroid hormones that are produced in the body during stress. In vitro studies will test how neuroendocrine hormones interact with their receptors. Using newly available genomic resources and phylogenetic modeling techniques, this research will reconstruct and resurrect ancestral melanocortin receptors for functional experimentation in a model cell line. This research will resolve how specific genetic mutations from the ancestral melanocortin receptors have led to a highly specific receptor hormone relationship that now has a critical role in the ‘fight’ or ‘flight’ stress response in later-evolved vertebrate animals. This work will serve as an example of how to empirically investigate step-wise evolution of complex physiological networks. The Fellow will to gain technical training in an emergent theme of interdisciplinary scientific inquiry and meaningful experience with research, mentoring, and teaching. 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.