Erik C. Johnson, Ph.D. - US grants

Food availability is a dynamic aspect of most environments and places significant challenges on organisms to maintain constant energy stores. The consequences of energy shortage include changes in behavior and physiology that reflect changes in the allocation of energy. Part of the decision process on how energy is utilized depends upon the actions of the AMP-activated kinase, a highly-conserved molecule that becomes active during energy shortages. It is also clear that different cellular populations have differential responses during energy deprivation, although it is unclear the extent that the AMP-activated kinase partakes in these processes. This project takes advantage of the unique molecular and genetic tools available in the fruit fly, Drosophila melanogaster, to investigate how the AMP-activated kinase regulates behavioral and physiological changes during starvation conditions. This research will contribute new information regarding the cellular signals within defined neural and peripheral tissues that are responsible for generating specific behavioral and physiological changes to maintain energy homeostasis. The evolutionary conservation of this particular molecule, as well as the conservation of behavioral responses to starvation, indicates results of this research will have broad applications, from pest management to the development of potential novel therapeutics. In addition to offering insight into the cell-specific roles of the AMP-activated kinase, this research project will be used as a vehicle to extend research opportunities to undergraduate students and enhance professional development of faculty at a primarily undergraduate institution, Francis Marion University. Lastly, this project will involve the training of graduate students.

This Major Research Instrumentation award funds the acquisition of system upgrades for a Zeiss LSM 710 confocal microscope at Wake Forest University. The instrumentation enables faculty, postdoctoral fellows, graduate students, and undergraduates to study and publish important findings on brain plasticity; hormonal regulation of plant development; stress response systems, gene expression, and protein localization in Drosophila; mechanisms of DNA repair, protein complex formation, protein oxidation, and posttranslational modification. The requested accessories permit live-cell, dynamic, and multi-label experiments and enable more educational opportunities. Consistent with WFU's mission to strengthen connections beyond campus, the LSCM is also used by regional investigators for research and education, and is utilized during outreach workshops. The results of these research and teaching efforts will be broadly disseminated through abstracts and peer reviewed publications, as well as by active participation of students and faculty at professional meetings.

The mechanisms of how organisms maintain metabolic homeostasis in light of significant environmental variation in food availability are not completely understood. Of particular interest of the field are the underlying mechanisms that form homeostatic responses to starvation. This research project will take advantage of the tractability of the model organism, Drosophila melanogaster and powerful molecular and imaging tools to address fundamental questions regarding metabolic decisions. One principal outcome of this proposal is to enhance understanding of the conservation of these metabolic networks. Preliminary results suggest that these networks are very likely to be highly conserved, and may therefore be leveraged for many practical applications, ranging from therapeutics to pest management.

Preliminary data from the PI supports the hypothesis that the energy sensor, AMP-activated protein kinase (AMPK) regulates the secretion of Adipokinetic Hormone (AKH), which functions to mobilize energy stores and is required for behavioral and physiological responses to nutrient limitations. This project will investigate: i) Functional mechanisms of hormonal signaling on AKH cell physiology; ii) Connections between hormonal signaling systems and AMPK; and iii) Regulatory mechanisms of AKH cell excitability. The planned experiments in this proposal will contribute new information into the cellular signals within a defined cell population, which is required for generating specific behavioral and physiological changes to maintain energy homeostasis. This research project will also be used as a vehicle to extend undergraduate research opportunities to students, and also to faculty at regional institutions. These opportunities will provide research opportunities to underrepresented populations at both the faculty and student level. This seamless integration of research and education will have broad impacts, in providing the benefits of undergraduate research opportunities to a diversity of students.