Transcriptional regulation of vertebrate development
We are interested in the networks of gene activity that control tissue and organ formation in the vertebrate embryo. The correct regulation of gene activation and repression is crucial both for cell types to become established during embryonic development and for on-going differentiation of stem cells in the adult. Conversely, deregulation of gene expression may lead to cancerous changes and other diseases. Understanding the programs that control gene expression and underlie cell differentiation is thus central to many aspects of human health.
Our main focus is on gene regulation during the formation of mesoderm and endoderm – two cell types that form in the early embryo. Mesodermal cells will go on to form tissues such as blood, muscle and bone, whereas endodermal cells will form liver, lung, pancreas and gut. By identifying the programs of gene regulation that lead to the formation of these cells types we hope to be able to recapitulate them in the lab and generate cells that could be used for repair and replacement of damaged tissues in humans. We also investigate what happens when gene expression is deregulated in cancer to identify drug targets.
We use a combination of approaches to study this, including experimental embryology, molecular biology, genomics, proteomics and computational biology in a variety of systems including zebrafish, mammalian stem cells and cancer cells.
Current PhD students
Sarah Kendall
Reuben Yaa
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PhD Student
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Projects
Transcriptional networks during zebrafish mesendoderm formation
We use genomics approaches such as ChIP-seq, RNA-seq and 4C-seq combined with embryological experiments, including genome editing and transgenic reporter assays, to characterise the networks of transcriptional regulation that drive mesoderm and endoderm formation in the early zebrafish embryo. Using these approaches we are generating an experimentally validated gene regulatory network for early mesendoderm formation.
Transcriptional regulation in cardiovascular development
Using genomics and proteomics approaches in differentiated mammalian embryonic stem cells, we have identified several transcription factors and their binding partners that play a role in the formation of cardiac cells. We are investigating how these transcription factors are regulated, how their binding partners modulate their activity and what their downstream targets are, in order to better understand the networks of transcriptional regulation that drive cardiac cell fate.
Transcriptional regulation of cancer progression
We have a long-standing interest in the T-domain factor, T/Brachyury, which plays a central role in early embryonic development. It also has a role in various cancers and is up-regulated, for instance, in chordoma, a rare cancer that forms along the spine, and is associated with metastasis of various cancers, such as lung and breast cancer. We are using a combination of genomics and cell biology to investigate the regulation of T/Brachyury in these cancers and identifying its targets to ask how it exerts its effects.
Publications
Collaborative projects
DanioCode and DanioPeaks
In collaboration with Professor Ferenc Mueller, Professor Boris Lenhard and an international group of scientists we are developing a community resource to annotate and display the functional elements in the zebrafish genome. More here.
Epigenetic regulation of muscle regeneration
In collaboration with Dr Robert Knight, in the Division of Craniofacial Development and Stem Cell Biology, we are using ChIP-seq and RNA-seq to profile the epigenetic landscape and gene expression changes that occur in muscle stem cells as they migrate to sites of injury.
If you would like to contribute to any of these projects please contact Dr Fiona Wardle.
People
PhD Student
Reader
Projects
Transcriptional networks during zebrafish mesendoderm formation
We use genomics approaches such as ChIP-seq, RNA-seq and 4C-seq combined with embryological experiments, including genome editing and transgenic reporter assays, to characterise the networks of transcriptional regulation that drive mesoderm and endoderm formation in the early zebrafish embryo. Using these approaches we are generating an experimentally validated gene regulatory network for early mesendoderm formation.
Transcriptional regulation in cardiovascular development
Using genomics and proteomics approaches in differentiated mammalian embryonic stem cells, we have identified several transcription factors and their binding partners that play a role in the formation of cardiac cells. We are investigating how these transcription factors are regulated, how their binding partners modulate their activity and what their downstream targets are, in order to better understand the networks of transcriptional regulation that drive cardiac cell fate.
Transcriptional regulation of cancer progression
We have a long-standing interest in the T-domain factor, T/Brachyury, which plays a central role in early embryonic development. It also has a role in various cancers and is up-regulated, for instance, in chordoma, a rare cancer that forms along the spine, and is associated with metastasis of various cancers, such as lung and breast cancer. We are using a combination of genomics and cell biology to investigate the regulation of T/Brachyury in these cancers and identifying its targets to ask how it exerts its effects.
Publications
Collaborative projects
DanioCode and DanioPeaks
In collaboration with Professor Ferenc Mueller, Professor Boris Lenhard and an international group of scientists we are developing a community resource to annotate and display the functional elements in the zebrafish genome. More here.
Epigenetic regulation of muscle regeneration
In collaboration with Dr Robert Knight, in the Division of Craniofacial Development and Stem Cell Biology, we are using ChIP-seq and RNA-seq to profile the epigenetic landscape and gene expression changes that occur in muscle stem cells as they migrate to sites of injury.
If you would like to contribute to any of these projects please contact Dr Fiona Wardle.
Our Partners
Biotechnology & Biological Sciences Research Council
British Heart Foundation
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