DISSERTATION RESEARCH: Energetic mechanisms underlying fitness consequences of immune responses

University Of Nebraska-Lincoln, Lincoln NE

Investigators

Abstract

This research tests the hypothesis that individuals with inefficient energy metabolism will have a decreased ability to fight infection, which in turn will decrease their future reproductive ability. Fighting infection requires individuals to invest energy in immune responses. These responses can deplete energy supplies that would otherwise be used for growth, maintenance, and reproduction, particularly when energy is limited. Individual organisms may be energy limited when nutrients are not available or when their genes do not allow efficient processing of nutrients into energy supplies. The research will also address questions about how fighting infection changes metabolic rate. By using the model genetic organism, Drosophila melanogaster, which has natural immune responses that are similar to humans, this project will generate critical information on how genetic variation in energy metabolism affects the ability of human cells to fight infection. This research will also be used to design new exercises for introductory biology laboratories that will help students synthesize information across diverse topics covered in introductory biology courses, from evolution to immunity and physiology. This project tests the prediction that the energy required to activate the immune system during development decreases the ability of individuals with inefficient energy metabolism to fight infection, and creating a resulting decrease in future adult reproduction. The project connects the effects of interactions between innate immunity and energy metabolism pathways at the organismal, molecular, and physiological levels in a well-studied genetic system. The experiments take advantage of a well-characterized set of genotypes, one of which has a disrupted mitochondrial-nuclear interaction that results in inefficient energy metabolism. Objective 1 will quantify whether flies with inefficient energy metabolism have lower infection survival and greater deleterious consequences for reproductive fitness after infection by a natural pathogen, Providencia rettgeri. Experiments will also modify the nutrient diet to further decrease the energy available for immune responses in all genotypes. Objective 2 will measure the activation of underlying molecular pathways and aspects of cellular energy metabolism to explain effects on tradeoffs between immunity and reproduction. Experiments include quantifying levels of antimicrobial peptide induction, measuring the amounts of key proteins in energy-sensing pathways, assessing the bacterial load during infection, and monitoring indicators of the cellular energetic state and organismal metabolic rate during infection.