Research Projects

Background: Immune factors are increasingly being recognized to have functions in the development and functioning of the nervous system. The complement system is a crucial component of the innate immune system and complement factors have been shown to control neurodevelopment by regulating neuronal differentiation, migration and synaptic pruning. Predictably, altered complement expression has been associated with conditions such as schizophrenia, depression and autism spectrum disorder. However, a detailed understanding of the role of complement factors in neurodevelopment and behaviour is lacking, and this can prove to be important in developing therapeutic strategies. Rationale/preliminary data: An unbiased transcriptomic analysis showed that several circadian genes are downregulated in zebrafish lacking functional complement factor c9. It is likely that C9 plays a role in circadian behaviour. Hypothesis: Innate immune complement factor C9 regulates circadian behaviour by controlling the development of relevant brain areas and neuronal subtypes. Experimental approach: 1. The expression of complement factor C9 will be analyzed in zebrafish larval brains at different stages of development by qRT-PCR and in situ hybridization. 2. Zebrafish c9 mutant fish will be subjected to circadian behaviour analysis in a high-throughput larval behaviour monitoring system. 3. Expression of circadian genes will be analysed in c9 mutant zebrafish by qRT-PCR. 4. Brain structure and anatomy will be analysed in c9 mutant zebrafish by immunostaining for specific markers. Significance to the field: This study will give a better understanding of the contribution of complement factors to neurodevelopment and circadian behaviour. Proper maintenance of the circadian rhythm is crucial for homeostasis, and perturbation in the rhythm can lead to conditions such as depression, memory deficits, and other mental health conditions. Similarly, dysregulated expression and function of complement factors has also been associated with various physiological and psychological conditions. The novel role of complement factors in circadian behaviour that this project will potentially uncover, could be one of the reasons underlying the mental health conditions observed in the absence of functional complement system. Better understanding of the contribution of immune factors to neurodevelopment, behaviour and disease could lead to the development of better therapeutic strategies in the long run.