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Cambridge NERC Doctoral Training Partnerships

Graduate Research Opportunities
 

Lead Supervisor: Frank Jiggins, Genetics

Brief summary: 
There are no cases where we know both the host and parasite genes underlying coevolution in natural animal populations, meaning key assumptions of models have gone untested, and the dynamics and immunological basis of coevolution are unknown. We propose to identify these genes in Drosophila melanogaster and a parasitic wasp.
Importance of the area of research concerned: 
The coevolution of hosts and parasites can drive extremely rapid genetic change, shaping infectivity and virulence. The central role that coevolution plays in evolution has led to a considerable body of theory and data. However, there are no cases where we know both the host and parasite genes involved in natural animal populations. As a result, key assumptions of models have gone untested, and the dynamics and immunological basis of coevolution are unknown. Therefore, you will identify the genes underlying the coevolution of the fruit fly Drosophila melanogaster and the parasitic wasp Leptopilina boulardi.
Project summary : 
The success of parasite infection typically depends on the ability of the parasite to suppresses the immune response, and this process likely underlies coevolution in many species. In Drosophila we have discovered that immune suppression depends on the combination of the host and parasite genotypes – a fundamental assumption of coevolutionary theory. You will identify the host genes involved and characterise how they interact with parasite genotypes. Knowing the genes underlying coevolution, you can test whether alleles that increase resistance are costly, and whether a genetic match between host and parasite alleles is required for infection. Theory predicts these properties can drive dynamic evolution, so we will track alleles in natural populations and test whether natural selection drives fluctuations in allele frequency through space or time.
What will the student do?: 
This project will exploit the powerful techniques of Drosophila genetics to understand the evolutionary process in natural populations. The first half of the project will be spent identifying the genetic variants in the Drosophila genome that determine whether or not parasites can suppress the immune response. This will rely on new tools being developed that allow the Drosophila genome to be easily edited, altering specific genes or nucleotides. The next part of the project will investigate the properties of these genes that will shape the course of coevolution. By creating flies that are genetically identical except for the specific changes in question, you can measure the effects of these polymorphisms on host fitness, and characterise how they interact with genetic variants in the parasite population. Finally, you can you can use publicly available datasets to examine how the frequency of these polymorphisms changes through space. This will involve bioinformatics and population genetic analyses.
References - references should provide further reading about the project: 
Leitão, AB, Bian, X, Day, JP, Pitton, S, Demir, E, Jiggins, FM 2019 Independent effects on cellular and humoral immune responses underlie genotype-by-genotype interactions between Drosophila and parasitoids. PLoS Pathogens. 15: e1008084
McGonigle, JE, Leitao, AB, Ommeslag, S, Smith, S, Day, JP, Jiggins, FM 2017 Parallel and costly changes to cellular immunity underlie the evolution of parasitoid resistance in three Drosophila species. PLoS Pathogens. 13: e1006683
Mark E J Woolhouse , Joanne P Webster, Esteban Domingo, Brian Charlesworth, Bruce R Levin Biological and biomedical implications of the co-evolution of pathogens and their hosts. Nature Genetics. 2002 569-77. doi: 10.1038/ng1202-569
Applying
You can find out about applying for this project on the Department of Genetics page.
Department of Genetics Graduate Administrator
Prof Frank Jiggins