Innovating Works

EvoGenMed

Financiado
Evolutionary genomics new perspectives and novel medical applications
To make for better diagnostics and safer applications of genomics we need a better understanding of our genome and how it functions. Until recently we thought we knew: intergenic sequence must be largely junk and mutations that, f... To make for better diagnostics and safer applications of genomics we need a better understanding of our genome and how it functions. Until recently we thought we knew: intergenic sequence must be largely junk and mutations that, for example, affect genes but not the protein (synonymous mutations) must be effectively neutral. This degenerate genome view accords with the nearly-neutral theory’s prediction that selection will be weaker when populations are small. But is this all there is to it? I shall investigate two new interrelated perspectives on genome evolution. First, I suggest that to mitigate errors, owing to our high error rates, our genome can be under stronger, not weaker, selection. Second, that errors might be a source of evolutionary novelty. Error mitigation, my team has shown, often involves selection on seemingly innocuous mutations such as synonymous changes. Remarkably, we discovered that selection to ensure error-proof splicing is possibly more prevalent on synonymous mutations when populations are small, making seemingly innocuous mutations stronger candidates for human diseases. I shall provide the first test of the new error-proofing perspective through comparative genomic analysis on synonymous site evolution. To investigate error as a source of novelty I shall consider whether expression piggy-backing (expression of a gene affecting its neighbors) forces rewiring of gene networks. Importantly, I shall translate our new understanding to enable better diagnostics and improved therapeutics. I shall develop a much-needed computer package to identify candidate disease-causing synonymous changes. In addition, knowing how synonymous sites modulate splicing will allow me to design better intronless transgenes. Transgenes must also be inserted in genomic regions immune to piggy-backing. I will examine transposable element related piggy-backing to characterize safe sites for therapeutic gene insertion and mammalian transgenesis more generally. ver más
30/06/2021
UBAH
2M€
Perfil tecnológico estimado
Duración del proyecto: 67 meses Fecha Inicio: 2015-11-18
Fecha Fin: 2021-06-30

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2021-06-30
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-ADG-2014: ERC Advanced Grant
Cerrada hace 10 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
UNIVERSITY OF BATH No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5