How does an essential histone variant effect changes in gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are not clearly known. It is well established that gene expression patterns are determined in part by the molecular signals transmitted by variation in the proteins that package eukaryotic DNA. Our aim is to understand new aspects of these mechanisms that revolve around how our DNA is packaged. This foundational knowl ....How does an essential histone variant effect changes in gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are not clearly known. It is well established that gene expression patterns are determined in part by the molecular signals transmitted by variation in the proteins that package eukaryotic DNA. Our aim is to understand new aspects of these mechanisms that revolve around how our DNA is packaged. This foundational knowledge will deepen our understanding of gene regulation in all complex organisms and will inform future efforts to rationally modulate gene expression patterns in agriculture, research and other important areas.Read moreRead less
Membrane attack complex/perforin-like proteins in developmental and neurobiology. This project will aim to use the fruit fly as a model system to understand how members of the perforin-like superfamily, a family of proteins more usually associated with mammalian immunity, function in embryonic and neural development. These data will eventually provide central insight into human diseases such as cancer and autism spectrum disorder.
Uncovering an evolutionary advanced mechanism of gene expression control. This project aims to uncover a new mechanism that activates gene expression in mammals, which involves unexpected connections between the core components of chromosomes and essential enzymatic machines required for the expression of genes. This project will generate new knowledge on the poorly understood process of how the extensive genomic information of multicellular organisms is selectively chosen to enable the expressi ....Uncovering an evolutionary advanced mechanism of gene expression control. This project aims to uncover a new mechanism that activates gene expression in mammals, which involves unexpected connections between the core components of chromosomes and essential enzymatic machines required for the expression of genes. This project will generate new knowledge on the poorly understood process of how the extensive genomic information of multicellular organisms is selectively chosen to enable the expression of only the required subset of genes. This will revolutionise our understanding of the mechanisms of gene control thereby shaping the field in the future. Significantly, this will allow new ways to manipulate gene expression that will impact biotechnology by providing new efficient ways to produce proteins or RNA. Read moreRead less
Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between the ....Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between these two important processes and will fill a significant gap in our understanding of how splicing quality control and nuclear RNA surveillance work. The project will also identify sequence features that trigger abortive splicing reactions and will thus help to improve the design of synthetic mRNAs.Read moreRead less
Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project ....Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project include revealing how accessory proteins help transcription factors identify their targets in the genome by reading epigenetic marks. This should provide significant benefits including improved design of artificial transcription factors to up- or down-regulate specific genes in research and agriculture.Read moreRead less
Uniting histone and transcription factor codes. This project aims to establish the general features of the “histone code”. It is well established that gene expression patterns are determined in part by the deposition, recognition and removal of post-translational modifications on the histone proteins that package eukaryotic DNA. This project proposes that this "histone code" is in fact a specific example of a transcription factor code. The project aims to enhance our understanding of the mechani ....Uniting histone and transcription factor codes. This project aims to establish the general features of the “histone code”. It is well established that gene expression patterns are determined in part by the deposition, recognition and removal of post-translational modifications on the histone proteins that package eukaryotic DNA. This project proposes that this "histone code" is in fact a specific example of a transcription factor code. The project aims to enhance our understanding of the mechanisms underlying gene regulation in plants and animals, and help to create improved strategies to optimise crop and farm animal properties and new-generation therapeutics.Read moreRead less
Estimation of non-additive genetic variance for complex traits using genome-wide single nucleotide polymorphyisms and sequence data. Finding genes for traits of importance in agriculture, ecology and human health depends on understanding the genetic basis of these traits. This project will investigate whether variation in traits in humans, cattle and wild sheep are influenced by gene-gene interactions.
The genetic architecture and evolution of quantitative traits. Most important traits are controlled by many genes and by the environment, however there is little knowledge of how many genes are involved in these complex traits and what their effects are. This project will describe the number of genes and their effects for complex traits in humans and livestock and explain how these genes evolve.
Rapid mapping of genes for complex traits. This project will develop a new resource that will allow rapid identification of genes controlling complex traits. This world-leading resource will improve knowledge of diseases like diabetes and neurological diseases.
Control of Wolbachia replication: maintaining a stable symbiosis. This project will use a comparative genomics approach to better understand how Wolbachia infections of insects are able to maintain themselves in insects without causing pathology. The results will allow us to better understand a distinguishing characteristic of an intracellular symbiont, namely replication control. The results also have the potential to lead to new approaches to insect pest control through a better understanding ....Control of Wolbachia replication: maintaining a stable symbiosis. This project will use a comparative genomics approach to better understand how Wolbachia infections of insects are able to maintain themselves in insects without causing pathology. The results will allow us to better understand a distinguishing characteristic of an intracellular symbiont, namely replication control. The results also have the potential to lead to new approaches to insect pest control through a better understanding of how Wolbachia might be used to skew insect population age structure.Read moreRead less