This project features the development of advanced photonic technology to attack a major unmet challenge in developmental biology. Embryonic morphogenesis results from a complex combination of gene expression, biochemical signaling, and biomechanics. While methods to evaluate the first two are well established, our knowledge of biomechanics of the embryo morphogenesis is poorly understood because of the lack of technical approaches. Elucidating the biomechanics underlying morphogenesis is essential towards understanding the interplay between mechanical regulation, gene expression and tissue patterning that drive embryogenesis, and will potentially lead to exciting innovations in therapeutic strategies and diagnostics for developmental defects. Current technology for tissue elasticity measurement is slow and invasive, thus cannot measure mechanical properties within living 3D embryonic tissue in-situ. This project will develop an all-optical approach (line-scanning Brillouin microscopy, LSBM) to fulfill this unmet need. LSBM allows rapid 3D mapping of the elasticity of embryonic tissue in-situ with high-resolution, non-invasive, and non-contact manner. After technology validation, I will use this technique to address an open question of the development field related to the role of tissue biomechanics in the process of neural tube closure. The central hypothesis of this grant is that the neural tube defect is related to the altered mechanical properties of tissue. Specifically, I will investigate the role of cellular activities, such as apical constriction, in the stiffness change of tissue during different stages of neurulation and specific genetic factors contribute to the abnormal changes in tissue stiffness. This K25 award, through its training and research components, will provide me with the skills to create a strong biological part in my future research, in which I will utilize the enabling technological capabilities to address the important needs in developmental biology. The overall effort will hasten my transition to being an independent investigator at the forefront of the interdisciplinary interface of technology development and biomedical research.
This project will develop and validate line-scanning Brillouin microscopy as a novel optical technology that uniquely enables non-perturbative and high-resolution mapping of tissue biomechanics during neural tube closure in real time. Integration with force transduction and distribution will allow fully studying the role of biomechanics in the regulation of embryo development. The K25 award will facilitate the candidate?s transition from optical science and technology development to biomedical research by providing the necessary training in developmental biology, biomechanics, and tissue engineering.
