Shape Matters: Engineering human stem cells models to understand the relationship between form and function in neural cells Dr Andrea Serio (Kings College London) presents his work on combining bioengineering, stem cell technologies and neuroscience to create complex models of the nervous system. Hosted by Dr Chris Spicer.
Event details
Abstract
Shape and function are two intimately linked properties in all living cells: the need to perform a certain function has shaped each cell to a specific and optimal shape, which in turns also influences how the cell manages its homeostasis. In cells with very polarised or complex shapes, like neurons and glial cells, this relationship is crucial as several key functions need to be performed across intricate cellular architectures, with challenges that sometimes cannot be met relying solely on diffusion of metabolites or components. Stem cell-based models and other in vitro experimental systems can effectively recapitulate key aspects of development, and have so far allowed a better understanding of key biological mechanisms underpinning human biology and disease. Access to these models has been particularly invaluable for basic and applied neuroscience.
However, conventional culture conditions often fail to approximate cell shape, and overlook some of the engineering constraints that cells in vivo face. Particularly in the case of specialised neurons covering long range connections such as spinal cord motor neurons (MNs), stem cell models often lack fundamental characteristics of their cytoarchitecture, including axonal length. MN axons can grow up to 1m in length, and this feature necessitates robust axonal transport, local protein translation and mitochondrial dynamics to maintain cellular homeostasis and functionality, which might not be faithfully captured by shorter cells in standard culture conditions.
To directly address this issue, we have developed a novel bioengineered platform to reproducibly obtain arrays of human motor axons ranging from micrometres to centimetres in length, which we have then used to systematically investigate the effect of cell size on axonal biology for the first time. We have discovered a link between length and metabolism in human MNs in vitro, where axons above a “threshold” size induce specific adaptations in cytoskeleton composition, functional properties, local translation and mitochondrial homeostasis of the axoplasm.
Our findings indicate the existence of a specific length-dependent mechanism that switches several homeostatic processes within human MNs to cope with extremely long axons. This has critical implications for in vitro modelling of several neurodegenerative disorders and shows the importance of physiologically modelling cell shape and biophysical constraints in vitro.
About the speaker
Dr Andrea Serio
Andrea first trained in Biotechnology at the University of Padova in 2003, before moving to the Università Vita-Salute San Raffaele of Milan in 2006 to pursue a MSc in Medical and Cellular Biotechnology. He then joined the University of Edinburgh in 2009, where he was awarded a studentship to work on patient-derived induced pluripotent stem cells (iPSCs) platforms to model glial neuronal interactions in genetic forms of Amyotrophic Lateral Sclerosis (ALS). After obtaining his PhD he then joined Prof. Molly Stevens lab at Imperial College London in 2013 as a postdoctoral research associate, and worked on establishing novel modelling platforms for neural circuits combining stem cell differentiation, tissue engineering and novel imaging approaches. He was appointed a lectureship at King's College London in September 2017, and moved to the Francis Crick institute in Nov 2019 for his secondment, where he established the neural circuit bio-engineering (NCB) group.
At KCL, Andrea's lab focuses on combining bioengineering, stem cell technologies and neuroscience to create complex models of the nervous system. They use these modelling platforms to both discover new fundamental mechanisms in neurobiology, and to better understand the molecular chains of event that lead to neurodegeneration. His interdisciplinary team focuses on a range of projects that seek to uncover the "engineering principles" of neurons, glia and complex circuitry, both to uncover new fundamental knowledge and to create new tools to model neural circuitry in vitro.