Project description
Toxin-antidote - a new class of selfish DNA elements in animals
Toxin-antidote elements are a form of selfish DNA that multiply in the cell without affecting the fitness (reproductive success) of the organism in other respects. For a decade, the only known toxin-antidote element in animals was found in C. elegans. Recently, researchers identified another such element in C. elegans and five novel elements of the same kind in C. tropicalis, a close relative of C. elegans. With EU-funding, this research team will investigate the underlying molecular mechanisms of animal toxin-antidote elements, and discover new elements in other species through a state-of-the-art gene mapping approach. A better knowledge about the spreading of selfish elements will help researchers find innovative ways to eliminate mosquito-vector driven diseases like malaria and Zika virus.
Objective
Toxin-antidote (TA) elements are a class of selfish elements that spread in natural populations by subverting the laws of Mendelian segregation (gene drive activity). For a decade, the only known TA element in animals was a paternal-acting element discovered in the nematode C. elegans. The lack of other examples perpetuated the idea that TA elements were extremely rare in animals. However, I recently challenged this view with two key findings 1) I genetically dissected a second TA element in C. elegans, the element sup-35/pha-1, and 2) I identified five novel TA elements in C. tropicalis, a close relative of C. elegans. Surprisingly, some of these novel TA elements can affect the fitness of adults and can antagonize each other mimicking the effect of balancing selection. Overall, my research strongly suggests that TA elements are much more common in animals than previously anticipated and raises critical questions about their origin, prevalence, mechanism of action, and contribution to speciation, all of which are largely unknown.
This proposal has three main objectives:
1. To dissect the molecular mechanisms underlying an animal TA element for the first time.
2. To identify and characterize novel TA elements in diverse nematode species.
3. To screen for TA elements in medaka fish.
My team and I will achieve these objectives by leveraging my multidisciplinary expertise in genomics, evo-devo, and biochemistry, as well as a state-of-the-art bulk QTL mapping method that I recently developed. Dissecting the molecular mechanisms used by natural selfish elements will help us design more efficient and specific synthetic drive elements that could target mosquito vectors spreading diseases such as malaria and Zika virus - global health burdens. I predict that we will discover and characterize many novel TA selfish elements in diverse species from nematodes to vertebrates. Our findings will stimulate new research areas in genetics, evolutionary biology, and medicine.
Fields of science
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Funding Scheme
ERC-STG - Starting GrantHost institution
1030 Wien
Austria