Defining the chromatin dynamics and its role in lymphatic vessel development and disease

Lymphatic vessels are no longer considered a passive conduit since their central role in a number of physiological processes has been determined. However, it is still unclear how the gene expression dictating the formation of lymphatic vessels is orchestrated.

Furthermore, only a limited number of molecular drivers for lymphoedema have been identified, the incurable disease resulting from the failure of lymphatic vessels to collect fluid, that affects about 200,000,000 people worldwide.Our preliminary data uncovered chromatin landscape in differentiated lymphatic endothelial cells.

Thus, we hypothesise that specific chromatin dynamics and interaction of non-coding regulatory elements drive lymphatic endothelial cell programming by inducing gene expression and their disruption contribute to lymphoedema.This project will determine the chromatin organisation and its role in inducing molecular factors to correctly programme lymphatic endothelium.

By an interdisciplinary approach we will combine strengths in zebrafish genetics with clinical databases to determine non-coding elements driving lymphoedema.

To determine the chromatin dynamics in forming vessels, we will use the newest omics technologies, microscopy advancements, zebrafish live imaging.

Together by combining discovery science with a focus on development genetics and omics approaches with clinically relevant data promises to uncover novel paradigms of lymphatic vessel formation and disease.