Technology transfer from basic research to medical diagnostics
The Future Cluster Nanodiag BW is developing technical solutions for molecular diagnostics using nanopores. To achieve this, the cluster consolidates research results from various disciplines that are on the verge of practical application. Based on nanopore technology, innovative products and services for the molecular analysis of epigenetic factors are being created. The current focus of application is the diagnosis and treatment of tumour diseases. However, epigenetic factors are also of great importance for many other conditions, such as neurodegenerative diseases like Alzheimer’s and Parkinson’s.
Epigenetics – a promising field of research
The High-Tech Strategy of the Federal Ministry of Education and Research (BMBF) identifies health as one of the major global societal challenges. The latest findings show that epigenetic factors play a significant role in the development of common diseases such as cancer, cardiovascular diseases, neurodegenerative conditions, and even infectious diseases.
The term epigenetics refers to changes in gene function caused by biochemical markings, without altering the underlying DNA sequence. For example, methyl groups (CH3-) can be attached to specific bases of the DNA. This can affect the speed and frequency of gene transcription, and therefore the activity of genes. Important cellular functions, such as the rate of cell division, are regulated in this way.
It's all about packaging
Histone proteins ensure that the DNA is properly packaged. The DNA is wrapped around histone proteins. In order to read the DNA, it must first be “unpacked.” When this happens is controlled by biochemical markings on the histone proteins. These so-called “post-translational modifications” are involved in regulating gene activity. This means that the chemical modification of histone proteins, for example, through methylation of the amino acid lysine, is also among the signals that have an epigenetic effect.
A Groundbreaking Analytical Method
Until now, the detection of post-translational modifications of histone proteins has primarily relied on labor-intensive immunoassays and mass spectrometry of short-chain peptides produced by enzymatic digestion of histone proteins. However, this method is expensive and also complex. Using miniaturised analysis systems based on nanopore technology, these histone modifications can be identified simply, quickly, and reliably. This enables the distinction of even peptides with identical mass (positional isomers), such as two singly methylated fragments of a histone protein that differ only in the position of the methylation. Achieving this with mass spectrometry requires a particularly complex procedure, where the peptide fragments are broken down a second time (tandem MS), with the additional risk of losing the modification.
The miniaturisation and simplification of the analytical method also offers the possibility of developing integrated systems that include sample preparation. We are working on automating enrichment and pre-separation methods such as immunocapture and nano-LC, as well as optimising them for nanopore analytics.
The Goal: Better Medicine for Everyone
The Future Cluster Nanodiag BW is pursuing the vision of realising miniaturised analytical devices based on nanopore technology and developing the corresponding procedures. This will lead to the creation of novel diagnostic products, innovative services, and spin-offs with high growth potential. The detection of epigenetic markers is set to become a new standard in diagnostics. This will significantly improve prevention, treatment, and aftercare of common and severe diseases.
The nanodiag Transfer Lab
In the spirit of an open innovation culture, Nanodiag BW is establishing a transfer laboratory. Its purpose is to consolidate nanopore technologies from basic research and prepare them for application through testing for specific tasks. This includes research methods, analytical techniques, and processes for manufacturing components.
