At November 11th 2022 Nienke van Dongen obtained her PhD Cum Laude.
Novel Biosensors for Early Cancer Detection - Development of Gold Nanoparticle and CRISPR/Cas Assays for the Optical Detection of Cancer Biomarkers in Urine
The earliest form of medical diagnosis is the practice of uroscopy. Although uroscopy is no longer as prevalent in modern medicine as it used to be, multiple diseases can still be diagnosed in urine.
This thesis presents optical techniques for early cancer detection in urine. However, instead of looking at the color or assessing the taste of the urine, the focus is on the biomarkers present in the urine. Biomarkers are biomolecules that, at certain levels, can indicate whether people are ill, what type of disease they suffer from, and what the stage of the disease is. The biomolecule we are interested in is deoxyribonucleic acid (DNA), more specifically, the methylated cytosine within the DNA.
Cancer, as a disease, starts with a change in the genome that results in the downregulation of genes involved in "normal" cell behavior. This genetic change can either be induced by a change in the DNA code (mutation) or a change that does not affect the genetic code but instead influences the way this code can be read. The latter is called an epigenetic alteration.
The epigenetic alteration we are studying in this Ph.D. thesis is the cytosine methylation in so-called CpG islands. As the name implies, cytosine methylation is nothing more than an added methyl group (-CH3) to cytosine, one of four bases of which a in the DNA polymer consists. This methylation mainly takes place in the promoter region of the DNA. If this promoter region is methylated, the genes upstream of this promoter region cannot be read. This process of inhibition happens in all cells of the human body, and in in a healthy body, it has the purpose of expressing specific genes selectively. For example, cytosine methylation ensures that muscle cells have different properties than lung cells, while the same DNA code is present in both cell types.
