Prof. Maxwell Hincke
From
Innovation in Medical Education & Cellular and Molecular Medicine, University of Ottawa - CA
In residence at
Avian Biology & Poultry Research (BOA) / Centre INRAE Val de Loire, University of Tours - FR
Host scientist
Dr Sophie Rehault-Godbert
PROJECT 1 (2018-2022)
Evolution of Innate Immunity at Biomineralized Barriers
In oviparous animals such as birds, embryonic development occurs in the egg, and after oviposition there is no further possibility of material exchange with the hen to fulfill the needs of the embryo. In such a context, the egg must contain all systems required for proper development of a living organism. Among these, the chorioallantoic membrane (CAM) is a novel placenta-like structure which is the nexus for many different physiological and metabolic processes including acid-base balance, breathing and calcium solubilisation from the eggshell that is re-allocated to assist bone and tissue formation in the embryo. Moreover, it is believed to play a pivotal role in innate immunity to protect the embryo, in close interaction with the eggshell and the eggshell membranes. The highly vascularized CAM occupies a strategic position, as it forms a lining under the eggshell and totally surrounds the embryo by the end of incubation. To date, the cellular and genetic basis for its protective mechanisms remains to be fully elucidated. Application of cutting-edge transcriptomics, proteomics and microbiology approaches, where the INRAE team "Défenses de l’Oeuf, Valorisation, Evolution" is an international centre of excellence, will be a fertile location for the STUDIUM experience of Professor Maxwell Hincke. Given the overlap in the research interests of Hincke with the INRAE team, and their remarkable potential to develop a new productive interaction together, there is tremendous potential for synergy and successful outcome of this project. Studying the role and the dynamics of the CAM in interaction with its surrounding tissues/structures throughout embryonic development is an ideal model for identification of novel bio-active molecules for biomedical and other non-food applications. These scientists will decipher the molecular mechanisms underlying innate immunity in the context of a model of decalcification of a biomineralized tissue (eggshell decalcification during embryonic development).
PROJECT 2 (2024)
Understanding the Molecular Actors that Mediate Vesicular Transfer of Mineral Ions for Skeletal Formation in the Developing Chick Embryo.
In oviparous animals such as birds, embryonic development occurs in the egg, and after oviposition there is no further possibility of material exchange with the hen to fulfil the needs of the embryo. In such a context, the egg must contain all systems required for proper development of an embryo. Among these, the highly vascularized placenta-like chorioallantoic membrane (CAM) is responsible for calcium solubilisation and transport from the eggshell to the embryo to assist bone and tissue formation.
However, the molecular actors and their mechanism of action responsible for this critical process are poorly understood. Elucidation of the role of extracellular vesicles within the highly vascularized CAM that contain calcium cargo for transfer to the mineralizing skeleton will be the focus of this STUDIUM project. Application of cutting-edge cell biology approaches, where the INRAE team "Biologie de l’Oeuf et Physiologie de la Poule" is an international centre of excellence, will be a fertile location for the STUDIUM experience of Professor Maxwell Hincke. Given the common research interests of Hincke with the INRAE team, and their productive interaction during his tenure as Le Studium Research Professor (2018-2022) that was focusing on the role of the CAM in innate immunity, there is tremendous potential for synergy and successful outcome of this new project. We will study the role and the dynamics of the CAM interaction with the eggshell and transfer of calcium ion to the mineralizing skeleton, a critical process that determines the health bone status of the hatched chicks, which is an ideal model for identification of novel bio-active molecules / mechanisms for biomedical and animal science applications. This project will decipher the molecular mechanisms underlying mineral ion transport from a biomineralized tissue (eggshell) which is in dynamic equilibrium with the calcifying embryonic skeleton.
Events organised by this fellow
Publications
Amorphous calcium carbonate (ACC) is an unstable mineral phase, which is progressively transformed into aragonite or calcite in biomineralization of marine invertebrate shells or avian eggshells, respectively. We have previously proposed a model of vesicular transport to provide stabilized ACC in chicken uterine fluid where eggshell mineralization takes place. Herein, we report further experimental support for this model. We confirmed the presence of extracellular vesicles (EVs) using transmission EM and showed high levels of mRNA of vesicular markers in the oviduct segments where eggshell mineralization occurs. We also demonstrate that EVs contain ACC in uterine fluid using spectroscopic analysis. Moreover, proteomics and immunofluorescence confirmed the presence of major vesicular, mineralization-specific and eggshell matrix proteins in the uterus and in purified EVs. We propose a comprehensive role for EVs in eggshell mineralization, in which annexins transfer calcium into vesicles and carbonic anhydrase 4 catalyzes the formation of bicarbonate ions (HCO[Formula: see text]), for accumulation of ACC in vesicles. We hypothesize that ACC is stabilized by ovalbumin and/or lysozyme or additional vesicle proteins identified in this study. Finally, EDIL3 and MFGE8 are proposed to serve as guidance molecules to target EVs to the mineralization site. We therefore report for the first-time experimental evidence for the components of vesicular transport to supply ACC in a vertebrate model of biomineralization.
Final reports
In oviparous animals such as birds, embryonic development occurs in the egg, and after oviposition there is no further possibility of material exchange with the hen to fulfill the needs of the embryo. In such a context, the egg must contain all systems required for proper development of a living organism. Among these, the chorioallantoic membrane (CAM) is a novel placenta-like structure which is the nexus for many different physiological and metabolic processes including acid-base balance, breathing and calcium solubilization from the eggshell that is re-allocated to assist bone and tissue formation in the embryo. Moreover, it is believed to play a pivotal role in innate immunity to protect the embryo, in close interaction with the eggshell and the eggshell membranes. Therefore, weakening of the eggshell during CAM-mediated decalcification is hypothesized to be compensated by upregulation of innate immune mechanisms. In order to characterize this role of the CAM during embryonic development, we performed transcriptomics, proteomics and bioinformatics analyses. This residence was also the opportunity to stimulate a new international dynamic collaboration towards investigating innate immunity in diverse biomineralized structures (shells, bone, corals).