PhD defence of Yuqing Huang: Biotic, abiotic and genetic perturbations in genetically variant Caenorhabditis elegans

Summary:

Throughout their life, organisms are affected by a range of perturbations including biotic, abiotic and genetic perturbations. Perturbation induced phenotypic differentiation is strongly determined by the genetic background and the underlying molecular and genetic response mechanisms. The model organism, Caenorhabditis elegans has been widely studied for perturbation studies. But so far, our understanding of the combined effects of biotic, abiotic and genetic perturbations is limited.

In this thesis, abiotic perturbation (heat stress (HS)) and biotic perturbation (Orsay virus (OrV) infection) were firstly combined in C. elegans. OrV susceptibility difference was found across different wild types of C. elegans. Transcriptome analysis revealed a list of potential candidate genes associated with HS and OrV infection.

Genetic perturbation (external human α-synuclein introgression) was applied to extended genetic backgrounds in C. elegans to investigate the perturbation-organism interaction. α-synuclein aggregation is a typical characteristic in Parkinson’s disease (PD), one of the neurodegenerative disorders (NGDs). α-synuclein recombinant inbred lines (αS-RILs) and introgression lines (ILs) were used as genetic resources. Transcriptomic and quantitative genetic approaches, including mediation analysis, and pharmacological intervention were applied to investigate the mechanisms underlying different phenotypes under genetic perturbation that affected by genetic variation. The influence of α-synuclein in genetically variant C. elegans was explored from different aspects, including the level of phenotypic change and genetic regulations.

In conclusion, the research in this thesis focused on perturbation-organism interaction, and explored the novel complexity from the aspect of perturbation combination and organism genetic variation, respectively. Through the extension of single perturbation to combined perturbation, single genetic background to variant backgrounds, more insight was obtained of the causal loci. In addition, the genetic perturbation represented typical protein aggregation that is involved in human NGDs, thereby increasing our understanding towards potential regulatory genes or pathways of human PD progression.