Cellular and molecular control of human embryonic alveolar development: towards lung regeneration

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During human embryonic development the lung is one of the last organs to become fully formed and ready for birth. When a baby is born prematurely normal embryonic lung development is interrupted and many premature infants require breathing support. Some of these children, particularly the most premature, develop a long-term lung condition called bronchopulmonary dysplasia (BPD). However, even premature infants who do not develop BPD frequently have decreased lung function throughout life. These facts illustrate that interruptions in embryonic lung development are not naturally caught-up during childhood growth. The Wold Health Organisation estimates that every year 15 million babies are born prematurely and that this figure is steadily rising. The aim of this proposal is to study the normal mechanisms of human embryonic lung development in order to identify new strategies to improve the lung health of premature infants.Surprisingly little is known about the cell types which work together to build a lung in the human embryo and even less is known about the cell-cell communication mechanisms that coordinate the process. Instead of working with animal models of lung development, this project will focus on studying human embryonic lung development using human embryonic lungs. This is now possible due to advances in molecular genetics and new techniques for growing human organs in the laboratory as mini-organs, or organoids. We will identify the different cells that are involved in building the lung and determine the signals that these cells use to communicate with each other. This study will provide a base-line for normal human lung development, allowing us to identify points for which therapies could be developed to promote lung maturation. In addition, during this project we will improve our techniques for growing human mini-lungs in the laboratory. These mini-lungs will provide a system for us to investigate the genetic causes of some premature lung conditions like BPD. These genetic experiments will assist with the development of new markers for the disease helping doctors to determine which premature babies are at risk. In addition, they will provide a system in which treatments to reduce the effects of BPD, and other lung problems associated with prematurity, can be tested.