Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput ge ....Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput genomics. The expected outcomes will overturn our current view on enhancer evolution and reposition our understanding of how enhancers are functionally encoded in the genome. The work is an important contribution to understanding cellular complexity and species evolution with wide-ranging impact in genetics.Read moreRead less
Multilevel selection and the integrity of mitochondrial DNA. This project aims to investigate the evolutionary conundrum of how and why organelles remain asexual. The widespread occurrence of sexual reproduction suggests that sex is beneficial to organisms. Yet we all carry an ancient genome that never had sex, the mitochondrial genome (mtDNA). Theory predicts that mtDNA should no longer exist, because without sex it accumulates deleterious mutations and cannot accumulate beneficial ones. Yet mt ....Multilevel selection and the integrity of mitochondrial DNA. This project aims to investigate the evolutionary conundrum of how and why organelles remain asexual. The widespread occurrence of sexual reproduction suggests that sex is beneficial to organisms. Yet we all carry an ancient genome that never had sex, the mitochondrial genome (mtDNA). Theory predicts that mtDNA should no longer exist, because without sex it accumulates deleterious mutations and cannot accumulate beneficial ones. Yet mtDNA does not suffer mutational meltdown and is shown to adapt. This project will explain how, proposing that the combination of two traits, uniparental inheritance and multiple genomes per cell, make up for the lack of sex. This project expects to provide an explanation for the evolutionary question of what keeps mitochondria healthy, important as mitochondria affect ageing and health.Read moreRead less
Using venoms to map critical and evolutionary conserved vulnerabilities. We have developed and applied new functional genomic approaches to study venom evolution. Using CRISPR screening, we find that unrelated venoms act on cells by exploiting the same vulnerabilities. By functionally mapping these vulnerabilities for all venom classes, we can begin to develop universal venom antidotes. Conversely, much of what we know about venom mechanisms comes from a small percentage of the biodiversity with ....Using venoms to map critical and evolutionary conserved vulnerabilities. We have developed and applied new functional genomic approaches to study venom evolution. Using CRISPR screening, we find that unrelated venoms act on cells by exploiting the same vulnerabilities. By functionally mapping these vulnerabilities for all venom classes, we can begin to develop universal venom antidotes. Conversely, much of what we know about venom mechanisms comes from a small percentage of the biodiversity within a venom, and we have developed genomic tools to study the venom “dark matter”. This work will lead to the full molecular characterisation of venom biodiversity, and new venom components will be useful for research or as novel medicines.Read moreRead less