Neural tube defects are among the most common birth defects and affect more than 500,000 infants worldwide each year, resulting in severe health problems, including paralysis of legs, brain damage, and even death. Now Professor Yubing Sun of our Mechanical and Industrial Engineering Department has received a $400,000 grant from the National Science Foundation to develop a series of engineered tools to enable the investigation of the poorly understood mechanism that causes neural tube defects.
Since this defect-triggering mechanism is very difficult to study using animal models, Dr. Sun explains that “developmental biologists have been using animal models like frogs or fruit flies to understand human development for centuries. Now it is the time to move on to study human development using human cells.”
Of course, using human embryos has great technical and ethical barriers, and therefore his research “will combine micro-engineered tools with human pluripotent stem cells to recapitulate the cell and tissue behaviors during neural development.”
These new tools will not only provide researchers with the ability to perform less-costly experiments while avoiding using animal subjects, but also uniquely allow researchers to determine the mechanical effects on neural tube formation.
Sun is the head of the UMass Laboratory for Multiscale Bioengineering and Mechanobiology, which applies and integrates fundamental engineering principles – such as manufacturing, biomechanics, materials science, and micro- or nano-engineering – to understand and harness the mechano-biology of stem cells for modeling currently incurable human diseases and for applications in regenerative medicine.
Sun’s NSF abstract notes that, to develop novel approaches for the prevention and diagnosis of neural tube defects, a fundamental understanding of the development of the central nervous system is required. Using animal models, researchers have unraveled the first stage of central nervous system development, meaning genetic and biochemical factors that regulate neural induction. Recent studies suggest that the cell-fate decision in the neural induction is regulated by biomechanical cues. However, this mechanical mechanism is poorly understood and very difficult to study by using animals in experiments.
During Sun’s research project, his team will collect fundamental data on how the mechanical environment of the cells changes their behavior during neural tube development.
“This project will test the hypothesis that mechanical interactions dictate morphogenic events in neural development,” says Sun. “Our previous work discovered that micro-patterned cell-culture environments can cause human cells to mimic the spatial patterning of neuro-epithelial cells and neural plate border cells, and thus will be used to model neural induction.”
As Sun’s research abstract explains, his team will investigate the mechano-transduction pathways in neural induction, thus focusing on the functional involvement of YAP, BMP, and Wnt signals. Lastly, his team will develop a radial chemical gradient generation device, integrated with the micro-patterning platform, to interrogate whether biochemical gradient can also induce cell spatial patterning during neural induction, and whether cell shape and force act downstream of biochemical gradient or work independently to determine lineage specification.
As Sun concludes, “Using integrative microsystems with the capability to fine-tune the chemical and mechanical environment, this research provides for the first time a quantitative analysis of the interactions between biochemical and biomechanical cues in neural development.”
As the principal investigator in the new NSF grant, Sun will also include an important educational component in his research by engaging K-12, undergraduate, and graduate students with diverse ethnic backgrounds and genders to conduct this interdisciplinary bioengineering research, thereby encouraging these students from various educational levels to pursue science and engineering careers. One of the major efforts is to develop his new graduate course – “MIE 597MB: Molecular, Cellular and Tissue Biomechanics” – which will be offered every fall semester for seniors and graduate students.
Sun earned his B.S. at the University of Science and Technology of China in 2010 and his Ph.D. from the University of Michigan at Ann Arbor in 2015. (July 2017)