The lack of axon regeneration following spinal cord injury (SCI) diminishes patients’ quality of life and poses a significant economic burden on the society. This project aims to investigate the complex axon guidance mechanism following a SCI scenario by applying mechanical tension on the growth cones (GCs) of central nervous system (CNS) axons via novel magnetic nanoparticles that are functionalized with neuronal cell adhesion molecule. It is hypothesized that the complex interaction of chemical and physical guidance cues at the cytoskeletal (CSK) level can be modulated by mechanically activating specific signalling pathways, e.g. RhoGTPases. To test this hypothesis, mechanical tension will be applied to multiple GCs simultaneously, using a magnetic tweezers system integrated with a microfluidic culture device, which grants exclusive access to axonal areas. The effect of tension on axon outgrowth will be characterized as a function of chemical and mechanical environment, while examining the roles of Rho GTPase signalling and CSK structure in this mechanotransduction process. In essence, this project poses a biological hypothesis that can only be tested using a combination of sophisticated engineering methods. The results of this multidisciplinary project will provide a better understanding of axon elongation mechanisms and potentially become a promising therapeutic approach for SCI. The fellow is a mechanical / biomedical engineer with experience in microfluidic neuron culture and live cell microscopy; whereas the host is a world leader in single molecule biophysics. This project will not only contribute to the scientific competency of Europe by tackling a very relevant medical problem, but also provide the fellow an excellent opportunity to gain high quality scientific training and complementary skills, necessary to obtain an independent researcher position in the European Research Area.
Fields of science
Call for proposal
See other projects for this call