Digital Nanopore Sequencer
The aim of this project is to develop a so-called "interactome profiler" that provides information about molecular interactions in a cell and how the epigenetic modifications of molecules can influence the interactome. Through a highly parallel arrangement of nanopores and a digital readout, it can be used to analyze disease-associated epigenetic factors, such as methylation of DNA and the post-translational modifications of proteins. We will characterize blood-derived T cells and so-called extracellular vesicles (EV) for epigenetic modifications to identify promising biomarker candidates, thus preparing a basis for the future application of nanopores in liquid biopsy-based diagnostics.
A number of products and services are to be created and methods generated, which will be independently commercialized by the SMEs involved in the project:
1) As a technology supplier, manufacturer and distributor, Actome GmbH develops innovative assays that detect epigenetic changes with high sensitivity, quantitatively and in minute volumes in the picoliter range. With its software expertise in addition, Actome will assist in the application of bioinformatical methods and AI algorithms to identify crucial molecular interactions
2) Computomics GmbH will contribute with its expertise in machine learning as well as in sequence data analysis to the identification of biomarkers and will implement and provide a resource that can visually display genomic, epigenomic, transcriptional as well as phenotypic patient data and the correlations of these data among each other.
3) The start-up ScomicsGmbH, a spin off from the German Cancer Research Center (DKFZ) in 2014, uses the antibody microarray platform "scioDiscover" to investigate around 1,300 biomedically highly relevant proteins. For the identification of post-translational protein modifications in the context of non-invasive diagnosticsSciomics extends the analytical possibilities by a highly parallel screening of modifications such as methylation and acetylation and thereby contributes a world-leading multiplex platform for an antibody-based search for protein biomarker candidates.
4) Q-bios GmbH is specialized in the production of DNA polymerases for PCR applications. It will realize isothermal amplification under nanopore conditions, providing the recombinase polymerase amplification system and modifying the required enzymes to such an extent or performing protein modeling for enzymes with new properties that the system can also be carried out under the high-salinity conditions.
5) As a globally active series manufacturer of microstructured and nanostructured films, injection molded parts as well as injection molding inserts and functional surfaces, temicon GmbH is producing picoliter well chips for the project. Finally, the metallic coating of the chips will be investigated to enable electrical contacting.
A high scientific level and clinical relevance of the project are achieved by the following institutions:
The Albert Ludwigs University of Freiburg is one of the leading German research universities and the University Hospital of Freiburg is a world-leading university institution of maximum medical care and the fourth largest German university hospital. Epigenetics and oncology are among the most important research areas. In the project, the UKF is taking the first steps in implementing nanopore technology to answer clinical questions, e.g. in diagnostics for the detection of therapy-relevant epigenetic changes.
Hahn-Schickard acts as a research service provider and innovator and develops together with partners smart products, from the idea to manufacturing. In the subproject to detect protein interactions via the nanopore sequencer, Hahn-Schickard will further develop existing technologies and adapt them to the subsequent analysis format, e.g. with regard to the biomolecules used or the corresponding biological markers. Another important task is the subsequent optimization of the process and integration into an overall platform.