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
Regulation of histone methylation by polycomb-like proteins. This project aims to investigate how polycomb-like proteins regulate polycomb group (PcG) proteins and recruit them to their target genes. During the development of all multicellular organisms, PcG proteins are essential for keeping thousands of genes in a repressed state. PcG proteins are recruited to their target genes with the aid of their Polycomb-like protein cofactors, in a process that is poorly understood mechanistically. This ....Regulation of histone methylation by polycomb-like proteins. This project aims to investigate how polycomb-like proteins regulate polycomb group (PcG) proteins and recruit them to their target genes. During the development of all multicellular organisms, PcG proteins are essential for keeping thousands of genes in a repressed state. PcG proteins are recruited to their target genes with the aid of their Polycomb-like protein cofactors, in a process that is poorly understood mechanistically. This project will determine the mechanism that underpins the recruitment and regulation of PcG proteins by polycomb-like proteins. Outcomes will have relevance for most development processes of multicellular organisms.Read moreRead less
The Role of DNA Methylation in Transcription Factor Activity. Although it is well established that gene expression is closely correlated with DNA methylation, its role in regulating the activity of DNA-binding proteins remains unclear. It has recently been shown that Krüppel-like transcription factors (KLF) have distinct binding preferences for methylated DNA sequences. This project aims to investigate how the activity of transcription factors is dependent upon targeting of methylated DNA by def ....The Role of DNA Methylation in Transcription Factor Activity. Although it is well established that gene expression is closely correlated with DNA methylation, its role in regulating the activity of DNA-binding proteins remains unclear. It has recently been shown that Krüppel-like transcription factors (KLF) have distinct binding preferences for methylated DNA sequences. This project aims to investigate how the activity of transcription factors is dependent upon targeting of methylated DNA by defining the genome-wide set of sites and structural domains critical for binding. It also will explore the functional significance of these sequences using assays that investigate the importance of DNA methylation in KLF mediated cellular reprogramming to the pluripotent state.Read moreRead less
Engineering a chromatin looping factor for artificial gene regulation. This project aims to define mechanisms of chromatin looping and gene activation by a widely expressed mammalian protein. The project will establish if the functions of this protein are modulated by the binding of small molecules, whether it can act in conjunction with closely related proteins, and if post-translational modifications regulate looping and gene activation. Using protein engineering the project will develop synth ....Engineering a chromatin looping factor for artificial gene regulation. This project aims to define mechanisms of chromatin looping and gene activation by a widely expressed mammalian protein. The project will establish if the functions of this protein are modulated by the binding of small molecules, whether it can act in conjunction with closely related proteins, and if post-translational modifications regulate looping and gene activation. Using protein engineering the project will develop synthetic looping factors that can switch on a wide array of target genes. The project aims to answer fundamental questions about how proteins can establish and maintain physical loops in DNA to modulate gene expression. The project will also develop research tools that might ultimately correct diseases caused by the faulty expression of genes.Read moreRead less
The role of Roquin in microRNA function and decay. The aim of this study is to understand how microRNAs (newly discovered genetic components that control cell growth and survival) function and are regulated. The expected discoveries will help understand how common cancers including breast cancer and autoimmune diseases emerge, and will help develop cutting edge genetic technologies.