Nutritional factors can have profound influence on immune defense, but the mechanisms linking dietary nutrition to immunity are poorly understood. Work performed under the proposed project will establish the relationship between nutrition and defense from physiological and genetic perspectives, and will ultimately identify genes contributing to individual-specific alteration in immunity due to diet. The project will make use of the model insect Drosophila melanogaster, which has metabolic and immune systems that are highly conserved with homologous systems in vertebrates.
In Aim 1 of the project, D. melanogaster provided with diets of varying nutritional composition will be evaluated for resistance to bacterial infection (measured as immune system activity and suppression of bacterial proliferation) and tolerance of infection (measured as the ability to sustain health while infected). The experimental diets to be evaluated will vary in protein, sugar and fat levels.
Aim 2 of the project will test the hypothesis that specific immune and metabolic signaling pathways are linked during infection, such that activation of the immune system causes altered metabolism and energetic utilization. The IMD (immune system), JNK (stress response), and insulin-like (metabolism) signaling pathways will be genetically disrupted to test for cross-communication between processes during the early stages of an infection.
Aim 3 of the project will conceptually link the first two Aims in a study of naturally occurring variation. It is known that individuals in natural populations are genetically variable for both immune-related and metabolic traits. Experiments to be performed under Aim 3 will determine the degree to which resistance and tolerance phenotypes are determined by genotype-specific effects of diet (termed genotype-by-environment interaction). These interactions form the conceptual basis of personalized medicine, and understanding them will be crucial for advanced clinical therapeutics. Analysis of known polymorphisms and unbiased genome-wide association mapping will be employed to identify genes responsible for genotype-specific immunological alteration with diet. The data collected under all three Aims will provide novel and broadly comprehensive understanding of dietary effects on defense quality, with critical implications for clinical and evolutionary biology.
It is intuitively appreciated that dietary nutrition can influence resistance to infection, but the mechanisms connecting nutrition to defense are poorly understood. The proposed study will evaluate the impact of dietary nutrients on immune defense, will determine the genetic mechanisms linking nutrition and defense, and will identify genes contributing to individual-specific alterations in immunity attributable to diet. The work will contribute to understanding disease resistance and susceptibility in evolutionary and clinically relevant contexts.
|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; Lazzaro, Brian P (2018) Persistence of an extracellular systemic infection across metamorphosis in a holometabolous insect. Biol Lett 14:|
|Shahrestani, Parvin; Chambers, Moria; Vandenberg, John et al. (2018) Sexual dimorphism in Drosophila melanogaster survival of Beauveria bassiana infection depends on core immune signaling. Sci Rep 8:12501|
|Behrman, Emily L; Howick, Virginia M; Kapun, Martin et al. (2018) Rapid seasonal evolution in innate immunity of wild Drosophila melanogaster. Proc Biol Sci 285:|
|Lazzaro, Brian P; Fox, Gabriel M (2017) Host-Microbe Interactions: Winning the Colonization Lottery. Curr Biol 27:R642-R644|
|Howick, Virginia M; Lazzaro, Brian P (2017) The genetic architecture of defence as resistance to and tolerance of bacterial infection in Drosophila melanogaster. Mol Ecol 26:1533-1546|
|Schwenke, Robin A; Lazzaro, Brian P (2017) Juvenile Hormone Suppresses Resistance to Infection in Mated Female Drosophila melanogaster. Curr Biol 27:596-601|
|Akhund-Zade, Jamilla; Bergland, Alan O; Crowe, Sarah O et al. (2017) The Genetic Basis of Natural Variation in Drosophila (Diptera: Drosophilidae) Virgin Egg Retention. J Insect Sci 17:|
|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:|
Showing the most recent 10 out of 34 publications