Physiological constraint is a ubiquitous property of life. Constraints arise because organisms are complex and need to simultaneously execute many physiological processes, often with limited resources that can be acquired from the environment. The idea of competition among physiological processes underlies the concept of life history tradeoffs, but only rarely is the mechanistic basis for life history constraint understood. The proposed work is continuation of an ongoing project to study the genetic basis for variation in resistance to bacterial infection, the mechanistic basis for genotype- by-environment interactions in immunity, and the life history tradeoff between immune function and reproductive fitness in the model insect Drosophila melanogaster. The proposed project has two Aims. The specific objectives of the first Aim are to determine how dietary nutrition impacts resistance to infection through consequences on host and microbial physiology, and how genetic variation in both host and pathogen may determine the impact of dietary environment on infection outcome. The objectives of the second Aim are to understand how endocrine signaling that promotes reproductive investment simultaneously limits immune performance, to test the costliness of reproductive investment as a constraint on immunity, and to determine whether infectious pathogens can commandeer nutrients intended for the developing oocyte and use them to promote infectivity. The ultimate of objective of this work is to develop a synthetic model of host immunity that can integrate host and pathogen genetic variation, life history constraint and competing physiology, and environmental variability to predict the outcome of infection.
The degree of host resistance to bacterial infection is shaped by genotype and environment, and moreover is constrained by competing physiological demands such as the need to maintain reproductive fitness. The proposed study will determine how host genotype and environment interact to determine resistance to and tolerance of infection, with particular attention given to pleiotropy among reproductive, metabolic, and immunological processes. The study will have a mechanistic genetic focus with broader implication for the evolution of life history traits and physiological determination of infection outcome.
| Troha, Katia; Im, Joo Hyun; Revah, Jonathan et al. (2018) Comparative transcriptomics reveals CrebA as a novel regulator of infection tolerance in D. melanogaster. PLoS Pathog 14:e1006847 |
| Duneau, David F; Kondolf, Hannah C; Im, Joo Hyun et al. (2017) The Toll pathway underlies host sexual dimorphism in resistance to both Gram-negative and Gram-positive bacteria in mated Drosophila. BMC Biol 15:124 |
| Duneau, David; Ferdy, Jean-Baptiste; Revah, Jonathan et al. (2017) Stochastic variation in the initial phase of bacterial infection predicts the probability of survival in D. melanogaster. Elife 6: |
| Galac, Madeline R; Lazzaro, Brian P (2011) Comparative pathology of bacteria in the genus Providencia to a natural host, Drosophila melanogaster. Microbes Infect 13:673-83 |
| Fellous, Simon; Lazzaro, Brian P (2010) Larval food quality affects adult (but not larval) immune gene expression independent of effects on general condition. Mol Ecol 19:1462-8 |
