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.”

    • Developing an Open Source Imaging-Driven Multifunctional Bioplotter (IDMB) for next generation in vitro modelling

    Cell culture experiments offer unique advantages when trying to study biological mechanisms, which mainly come down to the ability to manipulate both the key cell players and their environment within an experimental set-up, in ways that in vivo experiments would not otherwise allow. This increased control arises from the fact that cell culture systems are inherently less complex than their in vivo counterparts. This reduction of complexity is both an advantage and a crucial limitation of these platforms, and in recent years we have witnessed a plethora of new technologies and tools introduced to increase complexity of cell culture experiments.

    Amongst these: stem cell differentiation and reprogramming to obtain the right “key players”, live imaging techniques to monitor their dynamic behaviour and interactions, and even bioengineering techniques to control their environment in both 2D and 3D. Thanks to these we can now start to perform more complex experiments that better recapitulate the biological processes we want to study, but we are still limited by our technical capacity to reliably construct complex arrangements of cell with determined architecture, and to effectively manipulate these complex cultures, which inversely scales with complexity itself.

    To overcome these limitations and study dynamic biological complex systems like neural circuits, developmental niches, tumour microenvironments, or bacterial biofilms we need new platforms that allow us to first construct complex architectures of live cells and ECM, then influence their behaviour & composition in a dynamic way, and finally separate them into relevant subpopulation for analysis. And, as biological systems are dynamic in nature, we need to achieve all of this, while monitoring the behaviour and changes in the composition of the culture.

    These capabilities currently do not exist within a single integrated platform, but the technologies necessary are available in the form of i) live imaging platforms, ii) cell-positioning tools, iii) bioplotters or 3D bioprinter and iv) microfluidic-based cell sorters. Particularly, the current technological gap is represented by the fact that while commercial 3D bioprinters and bioplotters can construct complex cultures, they do not allow to acquire live microscopy data, and cannot function as dynamic manipulation tools as they construct cultures without direct feedback. And while live imaging systems that can observe their dynamic behaviour are available, no single platform allows to directly construct or manipulate bioprinted live cell constructs while at the same time acquiring live data on the cell behaviour.

    The aim of this project is to capitalise on these different technologies and integrate them within one single prototype platform, that we have named Imaging-Driven Multifunctional Bioplotter (IDMB). This system will be an open-source platform, adaptable to any biology lab and will integrate the functionality of live imaging systems and cell bioplotters/manipulation systems to offer the possibility of plotting live cells and ECM in complex arrangements, as well as manipulate and analyse these complex cultures, in a dynamic way, guided directly by the imaging data. During this project we will construct and optimise a fully functional prototype of the IDMB system and obtain key proof-of-principle data of its application to in vitro modelling.

This Project is funded by the BBSRC Technology Development Research Fund (TRDF) and we are looking for a new team member to help us develop this new system!


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.

Scroll Up