DS04 - Vie, santé et bien-être

Molecular Programs for neurodegenerative disease Protein Biosensing – MolPro2Biosens

Submission summary

With increasing life expectancy, neurodegenerative diseases such as Parkinson’s or Alzheimer’s disease are expected to affect an ever increasing number of people, potentially putting severe strain on healthcare systems around the world. These diseases are challenging in term of diagnostic because of our inability to access and monitor the progression of diseases affecting the nervous cells of the brain. Recently, it was shown that the gastrointestinal tract and its innervation are not only affected by these neurodegenerative diseases but play a crucial part in them. The compelling corollary is that the enteric nervous system could serve as a surrogate to track brain diseases in their early stage, and that because the gastrointestinal tract is much easier to access than the brain,this opens up a new perspective even for routine screening procedures using stool samples or minimal invasive mucous biopsies. Still, such an approach will require extremely sensitive and robust molecular detection methodologies adapted to various biomarkers.
We therefore want to explore the enteric nervous system hypothesis through a contribution to the field of molecular diagnostics that could also have a more general impact in biomedicine. For the detection of nucleic acid biomarkers (DNA and RNA), dominant approaches are based on the capability to perform target molecules amplification by PCR and detection by fluorescence. State-of-the-art protein detection relies on ELISA approaches, for example using fluorescent signal amplification techniques. More often than not, robust diagnostic requires the detection of multiple biomarkers. Many areas of medicine would thus benefit from a generalized method detecting simultaneously, in one robust device, multiple targets present at extremely low concentration in physiological samples. Our aim is to develop a novel approach for ultra-sensitive point-of-care sensing device by building up on the advantages of molecular programming approaches and electronic readout. Molecular programming (MP) has been shown to perform complex chemical signal processing operations in isotherm solution and can be interfaced to various biomarker that will act as an ‘input’. The MP blocks that we will use here will essentially perform signal conversion, amplification, thresholding and multi-input comparison. The universal ‘output’ of these parallel MPs will be read by using novel nanoelectronic DNA sensors based on nanowires. In addition to nucleic acids such as microRNA, proteins from gastrointestinal tissues including b-amyloid peptides, a-synuclein and tau protein aggregates, playing central roles in neurodegenerative diseases, will be specifically investigated as candidate deported biomarkers for the progress of brain diseases. Specific panels for both diseases will additionally be supplemented based on the findings of proteomic approaches in transgenic mice and patients.

Project coordinator

Monsieur Alexis Vlandas (Institut d'électronique, de microélectronique et de nanotechnologie)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

IEMN Institut d'électronique, de microélectronique et de nanotechnologie
Department of Informatics and Microsystem Technology
GULLIVER
Enteric Nervous System Group

Help of the ANR 906,602 euros
Beginning and duration of the scientific project: - 36 Months

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