Descrizione del progetto
Antidoto alle tossine: una nuova classe di elementi del DNA egoista negli animali
Gli antidoti alle tossine sono una forma di DNA egoista che si moltiplicano nella cellula senza influire sul fitness (successo riproduttivo) dell’organismo sotto altri aspetti. Per un decennio, l’unico antidoto alle tossine conosciuto negli animali è stato trovato in C. elegans. Recentemente, alcuni ricercatori hanno identificato un altro elemento di questo tipo in C. elegans e cinque nuovi elementi dello stesso tipo in C. tropicalis, un parente stretto di C. elegans. Grazie al finanziamento dell’UE, questo gruppo di ricerca indagherà i meccanismi molecolari alla base degli antidoti alle tossine animali e scoprirà nuovi elementi in altre specie attraverso un approccio di mappatura genica all’avanguardia. Una migliore conoscenza della diffusione degli elementi egoisti aiuterà i ricercatori a trovare modi innovativi per eliminare le malattie causate da zanzare come la malaria e il virus Zika.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
1030 Wien
Austria