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Navigating lymphatic formation and function in health and disease

Objective

For many years, lymphatic vessels have been viewed as inert fluid conduits whose open structure allows for passive flow of antigens, proteins and cells from peripheral tissues to lymphoid organs. Yet, recent discoveries highlighting novel functions and heterogeneous origins of the lymphatic endothelium, call for reevaluation of the passive lymphatic-vessel paradigm. During the past decade, we have used the zebrafish (ZF) to detail the cellular and molecular events underlying the development of the lymphatic system. Our discoveries have greatly contributed to our understanding of the origins, specification and mechanisms of formation of lymphatic endothelial cells (LECs) in the developing embryo. In line with our past achievements, we now aim towards novel directions- to transform the adult ZF into an equally convenient model for the study of lymphatic diversity. The overall goal of LymphMap is to reveal the multiple regulatory levels that coordinate the formation and functionality of lymphatic vessels in health and disease. To this end, we will carry out a comprehensive research program characterizing four distinct aspects of lymphatic biology:
1.Cellular origins and molecular signature of LECs
2.Formation and specialization of organotypic lymphatics
3.Lymphatic vessels during organ regeneration
4.Lymphatic involvement in human disease
Our experimental strategy involves the combination of high-resolution imaging, global expression profiling and regeneration models in adult ZF, with analyses of human-derived LECs in various clinical settings. The important and unique aspects of our approach are the focus on in vivo dynamics, and the cross-organ comparative analysis, which will likely provide the much-needed knowledge on lymphatic diversity in health and disease. When completed, we anticipate that this work will be part of a new paradigm – no longer perceiving lymphatics as passive bystanders, but rather as orchestrators of tissue morphogenesis and regeneration.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins

Call for proposal

ERC-2018-COG
See other projects for this call

Funding Scheme

ERC-COG - Consolidator Grant

Host institution

WEIZMANN INSTITUTE OF SCIENCE
Address
Herzl Street 234
7610001 Rehovot
Israel
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 000 000

Beneficiaries (1)

WEIZMANN INSTITUTE OF SCIENCE
Israel
EU contribution
€ 2 000 000
Address
Herzl Street 234
7610001 Rehovot
Activity type
Higher or Secondary Education Establishments