Project description
Chromatin organisation as marker for cancer diagnostic
Epigenomic reprogramming is critical for cancer progression and metastasis formation It supports tumour heterogeneity, which hinders diagnostics and targeted therapy. The EU-funded PROCHIP project aims to study cancer heterogeneity at a single cell level based on chromatin architecture and to use chromatin alteration as a marker for cancer. The goal is to develop a super-resolution microscope with high throughput capabilities based on a miniaturised 3D fluidic network integrated into a glass chip. Imaging analysis of a large number of samples will allow the creation of specific phenotyping procedures required for personalised medicine. Ultimately, it should allow response and resistance prediction to targeted, individualised treatments.
Objective
Cancer is both a genetic and an epigenetic disease whose outcome is influenced by tumor microenvironment, which represents the major driving force of tumorigenesis causing the functional heterogeneity observed in most cancer types. Defining the 3D-organization of cancer-associated chromatin domains would represent a new frontier to decipher tumor heterogeneity. None of the currently available technologies permit to rapidly analyze thousands of cells and profile their chromatin organization at single cell level, as needed for medical diagnosis and therapeutic guidance.
The goal of the project is to build a high-throughput super-resolution microscope in a microfluidic chip smaller than a coin. With this device we will provide high resolution imaging of hundreds of cells at the diffraction limit and beyond, with minimal photo-toxicity.
Femtosecond laser micromachining allows fabricating with accurate precision optofluidic components as waveguides, microchannels and lenses in a glass substrate. We will integrate them in a single chip, to achieve the required illumination path for advanced fluorescence excitation and sample movement: in the same chip biological samples will be scanned along fluidic channels in a fully automatic fashion.
High-throughput data on chromatin distribution in hundreds of samples will be generated, allowing to decipher the pathogenic function of tumor heterogeneities in tumor progression. These data will be used as benchmarks for predicting differential responsiveness and/or resistance of cancer cells to targeted therapies opening brand new possibilities for medical diagnosis and therapeutic guidance.
The consortium is formed by young scientists from Universities in the field of photonics, computer sciences and epigenetics, and a leading company in microfluidics.
Fields of science
- natural sciencesphysical sciencesclassical mechanicsfluid mechanicsmicrofluidics
- natural sciencesphysical sciencesopticsmicroscopysuper resolution microscopy
- natural sciencescomputer and information sciences
- medical and health sciencesclinical medicineoncology
- natural sciencesbiological sciencesgeneticsepigenetics
Programme(s)
Funding Scheme
RIA - Research and Innovation actionCoordinator
00185 Roma
Italy