Research

Research in the Lab.

We are interested in how sex differences in immune tissue function can result in sex differences in survival: both to acute infections, and over a lifetime to determine longevity.  We want to find ways to target the immune system to promote healthy ageing in both sexes.

To answer these questions, we use the genetically tractable and rightly infamous Drosophila melanogaster (fruit fly). Our work uses genetics and microscopy to ask about the cellular and signalling mechanisms underpinning male-female variation in immunity and ageing, and we collaborate with colleagues in the Institute of Evolutionary Biology to better understand the evolutionary drivers for these sex differences.

Why do males and females respond differently to infection?

The sexes show profound differences in responses to infection and the development of autoimmunity. Dimorphisms in immune responses are found across the animal kingdom, from arthropods to vertebrates. Fruit flies demonstrate sex differences in survival to infection with a range of different pathogens (read more here). The mechanisms underpinning these sex differences are not well-understood, particularly the role for individual tissues. We are asking whether immune tissues have a sexual identity, and how sex differences in their function are regulated. How does the sex of individual immune tissues impact the outcome to infection? What other environmental factors influence immune dimorphisms? We are working on these questions in collaboration with the Vale lab, the Obbard lab, and the Jenkins lab here at UoE, and with David Duneau at Toulouse University.

Diptericin 18 h infection

Why do females live longer than males?

Females outlive males in many species; this is true in Drosophila, and in most mammals including humans (read more here). We want to understand why this is, and what role the immune system has in driving dimorphic longevity. Our research in this area falls under two main questions:

  1. How does innate immunity impact ageing?

Defective immunity is both cause and consequence of ageing. We want to understand how age-related inflammation and immune decline make individuals more susceptible to infection and death, and how this differs between the sexes.

  1. How do geroprotective drugs affect the sexes differently?

Biogerontology, the field that studies the biology of ageing, is focussed on finding drugs that can delay age-related disease onset, and promote healthy ageing. Geroprotective drugs often have different outcomes in males and females (read more here). We study why this happens, including how these drugs interact with the immune system.

 

tram guts
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How have state-sensing pathways evolved to influence lifespan?

Our work on ageing has included the role for diet and nutrient-sensing pathways (or ‘state-sensing’ pathways) such as IIS/mTOR in influencing longevity, in combination with other environmental inputs. This has led to a collaboration with Josh Moatt, Dan Nussey and Craig Walling on the theory of how responses to dietary restriction, including lifespan extension, have evolved (read more here), and we are currently testing predictions that arise from this work.

 

 

 
 

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