Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that ....Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that have identified the earliest marker of endocardial differentiation and devised the method to make endocardium from stem cells. Knowledge from this work will inform future research into growing and regenerating damaged tissue.Read moreRead less
Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family protei ....Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family proteins as specific effectors. This project will address a new paradigm in genetics that is likely to underpin development.Read moreRead less
Molecular definition of cellular states in the vascular endothelium. The endothelium is the main cell type forming blood vessels and spans across multiple cell states from stem/progenitor to a variety of terminally differentiated cells. How each of these cell states are defined at the molecular level is not known preventing the optimal formation and integration of blood vessels in bioengineered tissues. Using innovative single cell gene expression and chromatin accessibility studies combined wit ....Molecular definition of cellular states in the vascular endothelium. The endothelium is the main cell type forming blood vessels and spans across multiple cell states from stem/progenitor to a variety of terminally differentiated cells. How each of these cell states are defined at the molecular level is not known preventing the optimal formation and integration of blood vessels in bioengineered tissues. Using innovative single cell gene expression and chromatin accessibility studies combined with innovative analysis, we propose to define and validate each cell state at the molecular level.
This new knowledge would greatly enhance our ability to control the transition between cell states leading to a more widespread use of endothelial cells in bioengineering of tissues globally for many applications.
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