Area of Knowledge: LIFE SCIENCES
Zaida Alvarez Pinto (Samuel I. Stupp), Institute for Bioengineering of Catalonia (IBEC) · email@example.com
Elisabeth Engel Lopez, Institute for Bioengineering of Catalonia (IBEC) · firstname.lastname@example.org
The extracellular matrix (ECM) is a critical and often overlooked component of the resident central nervous system (CNS) microenvironment that plays a pivotal role in neuronal maturation, signaling, aging, and injury (1). The ECM serves multiple functions, including providing structural support and integrity, acting as a reservoir for soluble factors such as cytokines and growth factors, and mediating cellular signaling (2,3). It modulates the transduction of cell surface receptors that internalize signals that control a variety of functions, including neuronal migration, survival, neurite outgrowth, axon myelination, and circuit formation (4,5). In addition, it has been shown in recent years that the composition of the spinal cord ECM undergoes important changes in response to injury, creating an inhibitory environment that blocks both intrinsic and treatment-induced mechanisms of tissue regeneration and functional recovery. Our central hypothesis is that the presentation of a physiological, developmentally appropriate ECM cue will circumvent some aspects of the lesion after spinal cord injury. The present study is focused on understanding the cell extrinsic determinants that drive human motor neuron (MN) degeneration and limit neural tissue regeneration after traumatic spinal cord injury (SCI). Our proposed study aims to target some of the candidate ECMs of the native and injured spinal cord and understand their effects on MN survival, outgrowth, and maturation. We will first use biochemical purification and quantitative mass spectrometry (MS)-based proteomics to define the composition and nature of remodeling of the mammalian spinal cord matrisome in vivo. We will then leverage our combined expertise in iPSC technologies and biomaterials to establish ECM mimetic matrices that can recapitulate the architecture and modulatory activity of the physiological matrisome to facilitate the survival, growth and maturation of motor neurons (MNs) in vitro. Finally, our best combinatorial ECM approach will be injected into the mouse spinal cord after severe traumatic spinal cord injury (Figure 1). This project, which aims to unravel the complexities of spinal cord injury (SCI), is proudly supported by the Spanish Ministry of Science through the Proyectos de Consolidación.
Job position description
The candidate involved in this project will have the opportunity to be immersed in multidisciplinary activities in a variety of scientific fields, including neuroscience, biomaterials, chemistry, tissue engineering, and regenerative medicine. The candidate will characterize the identities of proteins that comprise the spinal cord matrisome in early postnatal, adult, and injured mouse spinal cords. These valuable datasets will highlight age-dependent matrisome changes and inform the design of developmentally appropriate ECM matrices for culturing iPSC-derived spinal motor neurons.
Culture and biochemical techniques for human iPSC-derived neurons will also be part of the candidate’s work to characterize the effect of native and injured ECM candidates on neuronal behavior in vitro. Finally, the candidate will be involved in the design of new hydrogels with orthogonal ECM candidates that promote neuronal sprouting, survival, and growth after severe contusion in a mouse model of SCI. Writing scientific papers and attending conferences is strongly encouraged. International visits to other research centers are offered. Thus, a thorough training in various skills (scientific writing, oral communication, IP protection, etc.) will also be proposed by the institution.