The group main focus is to create new platforms dedicated to Neural Circuit Engineering (NCE) and Neurotechnology and to use them to gain novel insights on how the nervous system works in health and disease
The projects in the lab are grouped within three complementary themes, ande below are examples of the scinece cuurently going on in the lab.
Understanding Neurobiology & Neurodegeneration with Bioengineering
- Longer Axons for Motor neurons in a Bioengineered Device to model ALS (LAMBDA): a bioengineered platform to better model motor neurone diseases
The questions of length dependent vulnerability of motor neurones (MNs) in amyotrophic lateral sclerosis (ALS), and how specific changes related to extremely long axons can present a molecular bottleneck for vulnerability, is important and cannot at present be systematically addressed with current in vitro paradigms. This project represents the first instance in which length-dependent vulnerability and changes in axonal transport and local translation can be investigated directly in vitro using patient-derived cells, combining bioengineered substrates, high-content imaging and advanced molecular probes.
We have several collaborative projects about to start, focused on patient iPSC-based bioengineered circuit platforms and drug-repositioning studies. Contact Andrea if you are interested!
Developing New Technologies for Modelling Neural Circuitry with Stem Cells
- Synaptosome on Chip (SyonChip): combining stem cell technologies, bioengineering and advanced molecular analysis to model the tripartite synapse in vitro
“SyonChip” is a discovery based project that combines stem cell differentiation, bioengineering, advanced imaging techniques and molecular biology to create a model of the aforementioned tripartite synapse. This permits transcriptome-wide characterization of i) the maturing synapse and ii) the effect of astrocytes on this fundamental process. SyonChip combines expertise in neuronal cells and live imaging, –omics approaches for neurobiology and microfabrication.
- Bioengineered Cortical Neuronal Network (BioCoNNet): a stem-cell derived bioengineered platform to recreate the human cerebral cortex in vitro
"BioCoNNet" is a new bioengineered platform that aims to recreate the complexity of human cortical circuits in vitro using stem cell derived neurons. It uses this neuronal network to understand how connections in cortex are established and maintained, and how they are lost in dementias."
- LIPS2 (Live-on-Live Integrated Imaging, cell Positioning, Patterning and Stimulation System): A novel platform for in vitro human Neural Circuit Engineering
Stem-cell based modelling for neuroscience has been established in recent years as a powerful tool to recreate human neurodevelopment and to study neurodegeneration in vitro with human cells. However, the power of in vitro modelling is limited by the gap in complexity between stem cell culture set-ups and the functional units of the nervous system, neural circuits.This gap is mainly due to the lack of technologies capable of controlling precisely both timing and position of multiple cell types in a culture across complex architectures.This project aims to narrow this gap by developing a novel integrated system for the precise positioning of cells and extracellular matrix (ECM) proteins on living neuronal cultures, while simultaneously performing live imaging-based functional characterisation. This system will allow recapitulating in vitro the timeline and interactions of human neurodevelopment and to dramatically increase the complexity of stem cell cultures while maintaining complete control and possibility manipulation.
Visualising & Controlling Dynamic Processes in Complex Cultures
- Modelling metabolic dynamics in Astrocyte-Neuronal interactions with iPSC-based models of neurodegeneration using quantitative lifetime imaging
We are interested in understanding the contribution of astrocytes to the pathological mechanism in neurodegenerative disorders. In particular, we are trying to understand how astrocytes influence and regulate the function of neuronal populations, by visualising the dynamic fluctuations in ATP, Calcium and mitochondrial function in general. For this project have developed live imaging protocols based on FRET-sensors and optogenetic indicators, visualised with Fluorescence Lifetime Imaging (FLIM) systems, which allow us to take live snapshots of metabolic dynamics in astrocyte and neurons cocultured on our bio-engineered substrates.