Gerbrand van der Heden received a Rubicon grant for his proposal "Molecular diagnostics; overcoming target inhibition in nucleic acid-templated ligation reactions".
Nucleic acids have the interesting property that they hybridize to complementary strands with high selectivity. Genetic disorders, often involving small changes in the DNA, can cause severe illnesses amongst which are Alzheimer’s disease and several types of cancer. This proposal describes a method to detect disease related nucleic acids using synthetic probes. Two specifically designed peptide nucleic acid fragments will recognize and hybridize to the target nucleic acid, subsequently reacting with each other at both ends, creating a circular construct. In this process a fluorescent signal is induced which will indicate the presence of the target. The sequence of events will also diminish the affinity of the formed product for the target, thus allowing the nucleic acid template to act as catalyst in multiple cycles of product formation. The catalytic role of the template will result in the amplification of the formed signal and will enable DNA/mRNA detection at very low concentrations. The development and application of this approach will ultimately allow the diagnosis of genetic disorders in a very early stage.
The research will be carried out in the lab of Prof.dr. Oliver Seitz, Humboldt University, Berlin.