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Laura Ballerini

 
Neurons and nanomaterials
How can an artificial material instruct neurons and influence their behavior? This is the main interest of Laura Ballerini's group, which is experimenting with new materials such as carbon nanotubes and using them as a substrate for growing neurons. Ballerini's lab has shown that carbon nanotubes can make neuronal networks more efficient, a discovery which could have important applications for neuroprosthesis and for the treatment of spinal cord lesions.
 

Laura Ballerinifull professor
 

Laura Ballerini graduated (MD) at the Università di Firenze, Italy in 1988. She was a Post-doc at UCL from 1991 and later became assistant professor in Physiology at the Biophysics Sector of the International School for Advanced Studies (SISSA-ISAS) of Trieste, Italy in 1995. In 2012 LB became full professor in Physiology at the Università di Trieste, Italy and since January 2016 is full professor at SISSA. She has been working for more than 15 years on the physiology of spinal cord neurons/ networks and she has vast experience in using a variety of experimental electrophysiological techniques and in vitro model systems. LB has provided important contribution to the understanding of spinal network physiology, plasticity and development. Recently, LB has been working on the interactions between living neurons and micro-nano fabricated substrates or bioactive-composite containing carbon nanotubes. She demonstrated that carbon nanotubes substrates boost neuronal network activity by enhancing neuronal and synaptic performance. The scientific strategy at the core LB research activity is the convergence between nanotechnology, chemistry and neurobiology. Such convergence, beyond helping understand the functioning and malfunctioning of the brain, can stimulate further research in this area and may ultimately lead to a new generation of nanomedicine applications in neurology.

 

Research Lines

Mechanisms governing the interface between carbon based growth substrates and neurons

Study of the biophysical interactions between membranes and nanomaterials (carbon nanotubes) in neurons/nanoscaffolds hybrids, focusing on the role of membrane lipid components (rafts) in mediating adhesion and neuronal responses to conductive nanostructures.

The impact of synthetic nano-scaffolds on single cell physiology and intercellular communication modulates the complex dynamics of cell adhesion, growth and proliferation. Carbon nanotubes (CNTs) are a privileged material to support the cultivation of neurons. Available within the Ballerini’s lab is the state-of-the-art investigation showing that nanotubes can affect cell behaviour and promote attachment, growth, differentiation and long-term survival of neurons. Neurons are electrically excitable cells that transmit and process information in the nervous system. Neurons continue to grow when placed on CNTs and can still carry electrical signals when stimulated by the CNTs. As a result, several nanotube-based neural applications are being developed, such as neural prosthesis for monitoring neural activity. These achievements represent the ‘tip of the iceberg’ that only hints at the potential of CNTs for neurons. Beyond a mere interface of neuronal signalling, we reported that CNTs are able to impact the nervous system at three different levels of complexity. At the single cell level, CNTs alter the electrophysiological responses of neurons, improving their computational power. At the synaptic level, CNTs guide and induce a massive increase in synaptic density and affect the short-term dynamic of neurotransmission, strengthening synaptic signals when activated repetitively. At the level of three-dimensional spinal cord explants CNT scaffolds drive changes in neuronal fibre elongation, morphology and elastomechanical properties. Further, CNT scaffolds are able to modulate the functional performance of neurons spatially far from the scaffold. Thus, the potential of nanomaterial/neuron hybrid endeavour includes the challenge of using an artificial submicroscopic man-designed device to co-operate to neuronal network activity, generating hybrid structures able to cross the barriers between artificial devices and neurons.

Nanostructured bio-synthetic scaffolds and spinal networks

Development and multilevel application of three-dimensional biotechnological nanoscaffolds for tissue reconstruction and protection, from the simplified in vitro spinal segment to the complex, whole spinal cord system.

This project aims to exploit new concepts to obtain biomaterials for nerve tissue engineering. The goal is to develop a new generation of multifunctional implantable materials targeted to the treatment/repair of spinal cord lesion. By the convergence among different fields like nanotechnologies, polymer science and neurophysiology research, we will test nanostructured-bio-hybrid synthetic implants in cultured neuronal newtorks to address multiple key design criteria, such as biocompatibility, bioactivity, electrical conductivity, adequate rheological performance.

Growing neuronal networks with controlled 3D organization

Development of innovative platforms to artificially engineer neuronal tissues, to build customizable artificial three-dimensional neuronal networks with controlled cellular composition and networking.

This project will capitalize on state-of-the-art techniques in cell culturing and micro-nano manipulation, to envision solutions able to overcome the current limitations of standard in vitro culture methods. We wish to build artificial multidimensional cellular assembles to investigate specific properties of the DRG-spinal cord microcircuit. The customized 3D networks will allow basic research, pharmacological studies, and will open a number of possibilities to study and manipulate the properties of selective neuronal microcircuits to study, for example, sensory transmission and modulation.

Graphene based nanomaterials and excitable cells

Study of the impact of graphene-based nanomaterials on excitable cell electrical behaviour and health, assessment of biocompatibility and of the graphene/biomembrane interactions. Further developments include exploring the effects of interfacing healthy and glaucoma retinal cells.

Graphene is the material with most superlatives: it is the best conductor of heat we know, the thinnest material, it conducts electricity much better than silicon, is 100-300 times stronger than steel, has unique optical properties, it is impermeable already as a monolayer, these properties can be exploited in many areas of research; new possibilities are being recognized all the time as the science of graphene and other two-dimensional materials progresses. These properties give realistic promise of creating a new, more powerful and versatile, sustainable and economically viable technology platform based on graphene and related layered materials. As a result, graphene research has already emerged as the top research front in materials science. However, due to the unique structure of graphene, many of the possibilities it offers are still poorly understood. We will investigate the biological processes influenced by nanomaterials and nanomaterials interaction with biological membranes. Single and multiple electrophysiological measures will be used in the case of neurons and cardiomyocytes to assess the electrophysiological effects of conductive nanomaterials on electrically propagating complex tissues.

Molecular neuroscience of motoneuron disease: insights into pathology and protection mechanisms

Study of the degenerative processes in ALS model G93A organotypic spinal cultures. We study the potential involvement in motoneuron progressive degeneration of microglia-synaptic cross-talk. We will test whether SOD1 mutation improves the vulnerability of motoneurons exposed to inflammatory treatment via altering synaptic signalling in pre-motor networks.

We wish to understand the molecular mechanisms which lead to motoneuron (MN) cell loss in a genetic animal model of ALS in order to clarify at which steps, within the complex series of events underlying neurotoxicity, novel experimental approaches targeted at reducing neuronal death are best implemented. One of the major breakthroughs in beginning to understand ALS molecular pathology has been the discovery of gene mutations in the cytosolic Cu/Zn superoxide dismutase (SOD1) gene in a small proportion of all fALS patients. This discovery has led to an animal model of the disease in which the human mutations are brought to overexpression in mice. Studies based on these ALS animal models have provided new insight on the disease processes involved in selective motoneurons’ degeneration as well as on the alterations in spinal networks, ultimately linked to the SOD1 mutated enzyme expression.

Selected publications

Sci Rep. 2015 Apr 24;5:9562. doi: 10.1038/srep09562

From 2D to 3D: novel nanostructured scaffolds to investigate signalling in reconstructed neuronal networks

Bosi S, Rauti R, Laishram J, Turco A, Lonardoni D, Nieus T, Prato M, Scaini D, Ballerini L.

ACS Chemical Neuroscience 2012, 3, 611-618

Carbon Nanotubes: Artificial Nanomaterials to Engineer Single Neurons and Neuronal Networks

Alessandra Fabbro, Susanna Bosi, Laura Ballerini, Maurizio Prato 

 
 

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