Killing time! How circadian immunity and resource availability interact during malaria infections

Project offered for Ker Memorial PhD Studentship in Infectious Diseases

Malaria infections famously run like clockwork. When synchronous parasite replication within red blood cells completes and progeny are released, fever is triggered and recurs at intervals of 24, 48, or 72 hours, depending on the Plasmodium species. Rhythmic replication is important for the within host survival of parasites and also for transmission to mosquito vectors. While malaria parasites synchronise their replication with each other, and with the host’s daily feeding-fasting rhythms, host immune rhythms are also proposed to affect parasite replication and transmission.

Explaining parasite rhythms requires answering fundamental evolutionary questions. For example, which host and vector rhythms select for rhythms in parasite traits? What fitness benefits and costs do parasites experience due to their rhythms? What trade-offs and constraints govern parasite rhythms? This project will use a uniquely tractable system (lab mice and rodent malaria parasites) to undertake experimental manipulations to determine how rhythms in resources that parasites acquire from the host’s food and rhythms in immune responses shape parasite rhythms and fitness.  

The student will work within this area and the project could take many directions, depending on the student’s interests, for example:

• While rhythms in innate immune responses are unable to cause rhythmic parasite replication, the parasite’s rhythm alters as infections progress which might be related to rhythmicity in components of the adaptive immune system.
• Innate immunity does affect parasite infectivity to mosquitoes. However, it is not known how important these rhythms are for parasite fitness compared to rhythms in mosquito physiologies.
• Recognising that host-parasite interactions are dynamic brings much needed ecological realism. For example, when in mixed infections, do the benefits of timing replication ‘early’ to be the first to secure rhythmic resources beneficial to parasites, or is desynchronising to avoid competition a better strategy, and do parasites adjust their rhythm according to their circumstances?
• Likewise, both parasites and mounting immune responses are energetically demanding for hosts. How do forms of resource limitation (such as protein deficiency and anaemia) impact on the rhythms of host and parasite? 
• There may be opportunities to follow up results from lab experiments using samples collected from controlled human malaria infection studies.

Training and skills

Skills and training will depend on the student’s particular interests and the research directions they choose, but are likely to include:

• Experimental design
• Conceptual grounding in immunology, evolutionary ecology and chronobiology
• Experimental design, statistical analysis and interrogation of large data sets
• Basic parasitology, immunology, and animal handling techniques
• Mentoring undergraduate students and teaching
• Networking abilities, including conferences and building collaborations

Training opportunities in transferable skills provided by relevant doctoral training programs will be available to the student. Skills will equip the student well for a future in academic research or in policy and industry roles. In addition to the supervisors and their labs, the student will be supported by a thesis committee who will meet annually to review the student’s progress and development goals.