Sex differences in immune senescence and responses to geroprotective drug treatments
Lead Research Organisation:
University of Edinburgh
Department Name: Sch of Biological Sciences
Abstract
Ageing is the largest risk factor for the developed world's biggest killers, and the impact of age-related disease is one of society's foremost challenges. Defective immunity is implicated as both cause and effect of ageing. For example, inflammation is an essential response to wounding and infection, but when inflammation is misdirected, or chronic, tissues damage ensues and development of age-related disease is accelerated. The ability to resist infection also decreases with age, as has been demonstrated during the recent pandemic. Anti-ageing or 'geroprotective' treatments are under development, and many of these target the immune system.
Sex differences in immunity, age-related decreases in immune function, and lifespan are seen in human populations and across taxa (1). The mechanisms underpinning these sex differences are not well-understood, yet will have a profound impact on treatments that target those processes. We have demonstrated conserved sex differences in responses to treatments that target nutrient sensing pathways to maintain intestinal health (2,3). Our next goal is to understand sex differences in ageing of the innate immune system and responses to geroprotective drugs that target immune tissues. We want to understand the different investments males and females make in maintaining immune function, what fails on a molecular, cellular and tissue scale, and what can be rescued. We use a Drosophila model (4) to tackle the complex and key issues of the reciprocal interactions of sex, innate immunity and ageing. To do this we use several methodological approaches, including; infection and lifespan studies, in vivo microscopy, demographic analyses, genetics and transcriptomics.
The details of the study can be tailored to suit the applicant. Full training will be provided, and there will be ample opportunity to gain skills in any (or all) of: infection biology, pathophysiology, Drosophila functional genetics, transcriptomics (including single cell sequencing), microscopy, bioinformatics, and modelling approaches (with collaborators).
Sex differences in immunity, age-related decreases in immune function, and lifespan are seen in human populations and across taxa (1). The mechanisms underpinning these sex differences are not well-understood, yet will have a profound impact on treatments that target those processes. We have demonstrated conserved sex differences in responses to treatments that target nutrient sensing pathways to maintain intestinal health (2,3). Our next goal is to understand sex differences in ageing of the innate immune system and responses to geroprotective drugs that target immune tissues. We want to understand the different investments males and females make in maintaining immune function, what fails on a molecular, cellular and tissue scale, and what can be rescued. We use a Drosophila model (4) to tackle the complex and key issues of the reciprocal interactions of sex, innate immunity and ageing. To do this we use several methodological approaches, including; infection and lifespan studies, in vivo microscopy, demographic analyses, genetics and transcriptomics.
The details of the study can be tailored to suit the applicant. Full training will be provided, and there will be ample opportunity to gain skills in any (or all) of: infection biology, pathophysiology, Drosophila functional genetics, transcriptomics (including single cell sequencing), microscopy, bioinformatics, and modelling approaches (with collaborators).
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/T00875X/1 | 01/10/2020 | 30/09/2028 | |||
| 2885592 | Studentship | BB/T00875X/1 | 01/10/2023 | 30/09/2027 |