Molecular basis of parasite-induced disruption of host circadian outputs

Sleep/wake cycles are arguably the most important circadian behavioural output controlling many aspects of animal physiology. However, some infections induce disruptions to these cycles, leading to pathology. Sleeping sickness is an infection caused by the African trypanosome Trypanosoma brucei.

One of the most puzzling symptoms of this disease is the profound alteration in sleep patterns, which is now recognised as circadian disorder. This disease provides an ideal framework to study how pathogens disrupt host circadian behaviour.

I will use single-cell transcriptomics to profile the responses of key hypothalamic nuclei controlling circadian behaviour during infection.

I will also characterise the population of parasites residing in the brain compared to bloodstream parasites to identify mechanisms of glial activation, neuroinflammation, and parasite survival in the CNS.

These outputs will provide novel and unprecedented insights into the host-pathogen interactions in the hypothalamus that lead to disruptions of sleeping patterns.

My ultimate aim is to understand how pathogens interfere with the function of the central nervous system leading to changes in physiology and behaviour.

The outcomes of my fellowship will provide a new understanding of infection-induced circadian disorders and will reveal factors that can be exploited for intervention and treatment of infections affecting the brain.