Understanding host-microbiome coevolution and genetic variation in immunity using an insect model system
Active Project Grant Awarded Last action
- Award ID
- R35GM154800
- Recipient
-
University Of North Carolina At Chapel Hill UEI D3LHU66KBLD5 Part of University Of North Carolina System Office
- Awarding agency
-
National Institute of General Medical Sciences
National Institutes of Health, Department of Health and Human Services
- Obligated
- $2,671,742
Award facts
- Assistance listing
- 93.859 Biomedical Research and Research Training
- Completion date 44% complete
- Place of performance
- Chapel Hill, NC 27599, USA
Award details come from USAspending.gov.
Description
- Abstract
- Microbiomes have been described as 'ecosystems on a leash,' because immunological control of the microbiome is critical for host health. Variation in the genes that produce the immune system has been linked to microbiome dysbiosis and to disease, and studying immune systems in the context of host-microbe coevolution has generated critical insights. However, we do not understand the evolutionary forces maintaining host genetic variation related to the microbiome or how immune systems coevolve with beneficial microbes. My research program takes advantage of several key features of an innovative animal model system: an insect called the PEA aphid. This animal reproduces asexually, and we can precisely manipulate bacterial microbiomes across asexual lineages by adding or removing specific strains and species of microbes. The aphid microbiome includes species of enterobacteriaceae that have clear benefits for their hosts including protection against pathogens and parasites. These aspects of our model system allow US to untangle the specific effects of host and bacterial genetic variation on the microbiome, and to study natural and ecologically- relevant host-microbe pairings. Importantly, my lab has generated key data on the patterns of association between microbes and host populations, and we have shown that genetic variation in the immune system governs the association with bacterial symbionts. Over the next five years, we will use techniques adapted from human innate immunology, functional and forward genetics, and dual-rnaseq of both host and microbes to understand the roles by which animal immune systems and beneficial microbes evolve in a BI-directional manner. Our preliminary data suggest that phagocytes control the density of bacterial infections, but that some strains of microbes have evolved to kill phagocytes to grow to high density. We will test a mechanistic model for the interaction between phagocytes and beneficial bacterial in the context of host and bacterial genetic variation. Simultaneously, we will use an F2 cross to determine what kinds of genes underlie host genetic variation in the microbiome, the patterns of molecular evolution at these loci, and importantly, whether these genes also govern resistance against often closely-related pathogens. Together, this work will address fundamental questions relevant to human health, including whether adaptation to beneficial microbes trades off with the ability to combat pathogens, and how control of the microbiome shapes microbial virulence. This work will establish a foundation for my lab's future efforts to develop a comprehensive picture of how natural selection shapes host traits related to the microbiome in a controlled and tractable model system.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $381,677 | |
| Amendment | $381,677 | |
| Amendment | $381,677 | |
| Amendment | $381,677 | |
| Amendment | -$1 | |
| Amendment | $1 | |
| Amendment | -$1 | |
| Amendment | $1 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $381,677 | |
| Amendment | $381,677 | |
| Amendment | $381,677 | |
| Amendment | -$377,555 | |
| Amendment | -$377,555 | |
| Amendment | -$377,555 | |
| Amendment | $377,556 | |
| Amendment | $377,556 | |
| Original award | $377,556 |
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Quick answers
Who received award R35GM154800?
R35GM154800 was awarded to University Of North Carolina At Chapel Hill by National Institute of General Medical Sciences (National Institutes of Health) on August 1, 2024.
How much is award R35GM154800 worth?
$2,671,742 has been obligated on R35GM154800.
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