Molecular Programs for neurodegenerative diseases markers Biosensing

• Applicants: Professor Dr. Sven Ingebrandt; Professor Dr. Karl-Herbert Schäfer
• Subject Area: Microsystems ; Biochemistry ; Biomedical Systems Technology ; Medical Physics, Biomedical Technology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 391107823

With increasing life expectancy, neurodegenerative diseases such as Parkinsons or Alzheimers 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 could possibly drastically improve diagnostic and patient wellness. 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 biomarkers 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 a-amyloid peptides, b-synuclein and tau protein aggregates, playing central roles in neurodegenerative diseases, will be specifically investigated as candidate deported biomarkers for the progression of brain diseases

• DFG Programme: Research Grants
• International Connection: France
• Cooperation Partners: Yannick Rondelez, Ph.D.; Alexis Vlandas, Ph.D.