Behavioural immunity in Drosophila melanogaster: empirical
studies and modelling of disease susceptibility
Supervisory team:
Main supervisor: Dr Nick Priest (University of Bath)
Second supervisor: Prof John Hunt (University of Exeter)
Dr Araxi Urrutia (University of Bath), Dr James Hodge (University of Bristol)
Collaborators: Prof Thomas Flatt (Lausanne), Prof Marc Tatar (Brown, USA)
Host institution: University of Bath
Project description:
Dietary restriction (DR) has been shown to extend lifespan and suppress reproduction in a diversity of
animal species [1]. But, the role of the animals’ feeding behaviour in mediating extended life and
improved health is unclear. A recent collaboration between the Hunt and Priest labs applying the
Geometric Framework (GF), shows that lifespan in this species is determined by the ratio of protein
to carbohydrates in the diet, not the calorie count [2]. Subsequent studies we have conducted show
that infection shifts the Protein:Carbohydrate ratio which optimizes fitness (Figure 1), and it results in
the rapid growth of naturally-occurring sugar-loving gut microbes. In general, the diets which result in
extended longevity also make animals more susceptible to infection. In addition, female reproductive
output is both diet- and infection-dependent, which helps explain the strong trade-offs known to
occur between fitness traits in this species [2].
This studentship is appropriate for those seeking interdisciplinary training and research. It combines
the fields of dietary science, infection and immunity, microbiology, animal behaviour and
mathematical biology. The goal of the studentship is to identify the mechanistic link between the
intake of specific nutrients (P and C), behavioural feeding responses to infection, and how those
feeding responses alter susceptibility to infection. It will employ GF in conjunction with an RNAi
candidate gene approach to identify genes underlying feeding responses to infection. The findings
will be further enhanced by developing mathematical approaches in which hypotheses about microbe
growth are tested by constructing realistic models and fitting them to data. Gene expression of male
and female flies on the different diets will be examined using RNA-Seq. The ultimate goal of this work
is to generate general mathematical methodologies for testing the role of diet in immunity, which we
hope to apply to other systems, including humans.
References: 1 Nakagawa, S et al. 2012. Ageing Cell 11: 401-409. 2 Jensen, K., McClure, C., Priest, N. K.
and Hunt, J. (2015). Sex-specific effects of protein and carbohydrate intake on reproduction but not
lifespan in Drosophila melanogaster. Aging Cell, 14: 605–615. doi: 10.1111/acel.12333
Figure 1: Evidence that infected flies benefit from consuming protein-rich diets. Nonparametric thinplate spline contour visualisations of the responses surfaces are displayed, which describe the effects
of protein and carbohydrate intake on lifespan, daily egg production and life reproductive success in
Drosophila melanogaster treated with sham control (no pathogen), pathogen challenge (heat shock
pathogen) and live infection (pathogen). Note that, contrary to the case for no pathogen or heat-killed
pathogen, the fitness peaks (in red) for pathogen-infected animals are highest at intermediate levels
of protein-rich diets, which matches the change in feeding patterns of infected flies in food choice
assays.