Interested individuals must follow the "how to apply" link on the Geosciences E4 Doctoral Training Partnership web page: http://www.ed.ac.uk/e4-dtp/how-to-apply
Summary
This project uses the genetically tractable model Drosophila melanogaster to address the concept that immune responses are costly, by linking physiological immune mechanisms with ageing and lifespan
Project background
It is long-proposed that immune responses are costly, but although the ‘costs’ of the immune system on reproduction, ageing and lifespan are often cited, they are not well-defined. Furthermore, in evolve and re-sequence studies, changes in allelic frequencies of immune-related genes correlate with the evolution of lifespan, but the link between specific immune functions and lifespan has not been resolved. Costs could arise from different actions of the immune system: upon infection, immune cells become energetically ‘selfish’, usurping energy/nutrients at the expense of other tissues. Immune responses can also potentially be costly through self-inflicted damage to the host. To understand the basis of the connection between ageing and immune function, it is key to link mechanism with theory, and to define what the cost of immunity means both in the short- and long-term for an individual. Understanding mechanisms underpinning costs will help to shed light on host-pathogen evolution, and will offer a route to understanding how to mitigate these costs in ageing populations.
We use the model system Drosophila melanogaster, which offers an unparalleled set of genetic tools including experimentally evolved lines, fully-sequenced panels of isolines and transgenic lines for manipulating gene expression.
Research questions
This project aims to:
1. Distinguish between the costs of investment in (baseline), and deployment of (acute responses), immunity, and correlate these costs with ageing and lifespan;
2. Resolve whether long-lived individuals invest more into feedback regulation of immunity, less damaging immune responses (eg barrier/cellular vs humoral immunity), or less energy-hungry immune responses than do short-lived individuals;
3. Test the theory that loss of negative immune regulation at older ages drives mortality by increasing costs to the host.
Methodology
The project will use Drosophila genetics and environmental manipulation, controlled infection studies, lifespan analysis, and assaying components of the immune system through functional genetics, transcriptomics, flow cytometry, and physiological assays . A reasonable timescale for this project would be:
- Year 1: Training, Analysis of chronic and acute, repeated immune challenges and lifespan (Q1);
- Year 2: Physiological analyses of immune regulation in long- and short-lived lines (Q2);
- Year 3: Analysis of decline of immune resolution in aged individuals (Q3).
Training
A comprehensive training programme will be provided comprising both specialist scientific training and generic transferable and professional skills. Specialist training will include Drosophila functional genetics, microbial culture and infection studies, transcriptomics, flow cytometry, physiological assays including metabolic assays, the use of R, and of multivariate statistics including mixed effects models.
Requirements
Candidates must be highly motivated with a keen interest in linking evolutionary biology and physiology. Previous experience with insect model systems, genetic analysis, biology of ageing or immune physiology would be an advantage but is not required.
www.ed.ac.uk/profile/dr-jennifer-regan
walling.bio.ed.ac.uk/
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