Sprouting of new capillaries from pre-existing vessels (angiogenesis) promotes the formation of almost all blood vessels during development, growth and tissue regeneration. Furthermore, imbalances in angiogenesis contribute to numerous disease states, including cancer, blindness, arthritis and ischemic disorders. Recent studies have determined that angiogenesis involves coordinated sprouting of specialized endothelial cells with distinct cell-fate specifications and behaviours. Endothelial “tip cells” lead sprouting vessels, extend filopodia and migrate in response to gradients of the soluble ligand, vascular endothelial growth factor (VEGF). In contrast, “stalk cells” trail behind tip cells, do not actively migrate and generate a vascular lumen. The induction of specific endothelial cell phenotypes and angiogenesis involves the tight spatiotemporal control tip/stalk cell-specific gene expression. However, the cell-type-specific transcriptional mechanisms that control gene expression during angiogenesis are unclear. Combining advanced genomic and in vivo cell biological approaches in the zebrafish model system we have identified various tip/stalk cell-specific genes that play key roles during angiogenesis in zebrafish. This project will define the cis regulatory elements controlling expression of these tip/stalk cell-restricted genes in vivo. Furthermore, these cis-regulatory elements will be exploited to develop zebrafish transgenic tools that will allow the genetic manipulation tip/stalk cell gene expression and angiogenesis in vivo. This project will use molecular biological, cell biological, advanced genomic, zebrafish transgenic and in vivo live imaging approaches. Ultimately, this project aims to uncover a detailed transcriptional framework for the control of angiogenic sprouting in vivo.
Entry Requirements
Candidates are expected to hold (or be about to obtain) a minimum upper second-class honours degree (or equivalent) in a related area / subject. Candidates with experience using the zebrafish model system or with an interest in vascular developmental biology are encouraged to apply.
How To Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”
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