You are here : Home > REVEAL Project

Europe | Health & life sciences


REVEAL

Disruption of cellular homeostasis lies at the origin of many diseases and can manifest itself as aberrant structures, functions and behaviours in mammalian cells. Heterogeneity in phenotypes of cancer-initiating cells is a hallmark of liver cancer, tuning its aggressivity and resistance to treatment, making it the second highest cause of morbidity worldwide. 

Published on 5 January 2021


neuronal micRoscopy for cEll behaVioural Examination and mAnipuLation


 

Starting date : Jan 2021 > Dec 2024  Lifetime:48 months



Program in support : H2020

Next generation biophotonics methods and devices as research tools to understand the cellular origin of diseases



 

Status of project : in progress


CEA-Leti's contact :                         
Cédric Allier   
                                     

                                               

 

Project Coordinator: CEA-Leti 



Partners 

  • IPRASENSE
  • Ecole Normale Supérieure de Lyon
  • Ludwig-Maximilians-Universität München 
  • Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milano
  • ALS Automated Lab Solutions GmbH
  • Politechnika Warszawska 

Target market: Market of photonics systems for healthcare




Investment: € 5.9 mi

EC Contribution: N/A






 

Number of patentsn/a


Stakes

  • The last decade has seen instrumentation, biology and machine learning transformed. To embrace all these innovations altogether, the present project proposes to install a novel microscope at the interface of these fields. To this end, we introduce a concept of ‘neuronal microscopy’, a microscopy technique relying heavily on neural networks able to perceive, interpret, conjecture, infer, anticipate and act.
  • The present project intends to lay down the foundations of this ‘neuronal microscopy’ in the realms of 2D and 3D cell live imaging. We will develop the necessary tools and the first instruments that will demonstrate the feasibility and the power of this new microscopy framework. In particular, we will develop a ‘cell picking neuronal microscope’ that will allow us to detect and collect different subtype of liver cells that are due to become tumoral and analyse them ahead of tumour manifestation. 
  • This analysis will help us to characterize the cellular heterogeneity known to exist at the origin of liver cancer. It will provide a direct mapping between cellular phenotypes observed under microscope and gene expression present in the early stages of liver cancer.  Overall, we are thus defining a novel methodology, which gives a central place to neuronal microscopy in the understanding of the cellular origin of the diseases



OBJECTIVES


  • Disruption of cellular homeostasis lies at the origin of many diseases and can manifest itself as aberrant structures, functions and behaviours in mammalian cells. Heterogeneity in phenotypes of cancer-initiating cells is a hallmark of liver cancer, tuning its aggressivity and resistance to treatment, making it the second highest cause of morbidity worldwide. These variations are often too subtle to detect or are extremely rare events and highlight the urgent need for new biophotonics tools that are capable of reliably detecting these phenomena.  
  • To obtain evidence of the processes that cause tissue heterogeneity underlying liver cancer, in project REVEAL we propose to develop a 'neuronal microscope'- an instrument where hardware and software analysis are seamlessly integrated, and uses computational neural networks to determine cell trajectories, i.e. the evolution of cell phenotypes. The software relies heavily on the use of neural networks for image formation, cell analysis, cell fate prediction and decision making to i) image and analyse in quasi real-time, cell behaviours of thousands of cells in parallel ii) identify variations in cell-state indicative of disease origin, iii) pinpoint the location of the cell of interest and the hardware will allow it to iv) pick-up cells for bio-analysis as a final step. 
  • While the live cell imaging will provide information about the past of the cell, the molecular analysis would reflect the present biological state of the cell and the prediction algorithm would then suggest the future state of the cell. The framework we propose is disruptive - we imagine a future where live cell microscopy and biomolecular analysis will form a continuum to generate a comprehensive biological timestamp for any cell of interest; such a neuronal microscope will be invaluable for identifying mechanisms at the origins of a disease.
IMPACT

This projet has four main objectives :
  1. Develop a neuronal lensfree microscope
  2. Develop of a cell picking neuronal microscope
  3. Discover biological signatures at the origin of a specific disease (liver cancer) using a cell-picking neuronal microscope.
  4. Develop a 3D neuronal microscope 
As a result, the project will have the following impact
Specific impact 1 = Significant gain in understanding of inter- and/or intra-cellular processes
The project aims to provide disruptive tools and methodology to image cells and understand inter/intra-cellular processes. More specifically the project aims to develop a 'cell picking neuronal microscope' that will allow in combination with biological analysis (proteomics, genetics, etc.) to characterize the cellular heterogeneity known to exist at the origin of liver cancer. The challenge is to develop this novel molecular-imaging technique that can potentially let discover novel cellular mechanisms at the origin of a disease.
Specific impact 2 = Strengthen Europe’s industrial position in the biophotonics-related market for microscopes and research and development tools

The project aims to develop and bring to TRL 7 a new microscope that could be then commercialized by the industrials partners of the project.
In clinical research setting, its potential to impact research is not limited to oncology alone. The REVEAL project will have other impacts, in particular the following societal impacts: 
  • To identify mechanisms driving the initiation of a disease to thus design prevention strategies to minimize its occurrence.
  • To develop optimal targeted treatments minimizing at the same time side effects.
  • To design personalize medical interventions to increase successful treatment responses.
  • Increase patient well-being and cure rate.
  • Decrease the general cost of a disease in the society. 


Critically, it will deeply impact the biological laboratories that are developing the use of organoids and mini-tissues, stem and induced-pluripotent cell cultures. The latter systems are now increasingly promoted to reduce the need for using whole organisms such as mice for ethical considerations or for lack of access to patient-derived specimens for a large swathe of basic biological research laboratories. The neuronal cell-picking microscope could thus find use in the study of 2D and 3D culture systems aimed at studying the development or function of a particular type of disease, specific biological phenomena or the use of new culture systems for high-throughput drug screening