Analytical Neurochemistry and Clinical Chemistry
Today we have the possibility to map the individual human genome containing around 25,000 genes. These genes are located in the 23 pairs of chromosomes in all of the 252 various cell types in the human body that carries a nuclei.
The genome is more or less constant during the whole life and do not change with age and disease. By screening the genome though we can get information about our disposition to get certain illnesses such as cancers, diabetes, cardiovascular diseases, as well as psychiatric and neurodegenerative disorders. In order to have a chance to catch a disease (familial or sporadic) earlier than the first clinical manifestations we need to look for other markers. One way is to monitor the individual proteome, the expressed protein content in a tissue (biopsies or autopsy) or a body fluid (cerebrospinal fluid, plasma, dry blood spots, saliva, urine etc.) at a selected time point. The human genome could in principle code for over 1 000 000 proteins if we take into account all posttranslational modifications that can occur (over 450 different known today). In disease the protein levels may vary rapidly and may also affect other protein complexes by indirect mechanisms. We therefore take the advantage of modern proteomic methodology such as up-front selective sample preparation, liquid based multidimensional separation and high-resolution mass spectrometry to generate biochemical patterns of the protein and peptide content in the samples. By comparing patterns from patients with certain diseases with healthy individuals or even follow the same individual during treatment (e.g. pre- and postoperative or pre- and postmedication) we can identify potential biomarkers for disease. In combination with proteome analysis we also study the metabolome, either targeted or by monitoring the total metabolic profile of the individual. Molecules like amino acids, amines, sugars, carbohydrates, steroids and lipids changes rapidly in response to disease, food and drug intake, physical activities etc. It is also often possible to follow these changes in e.g. non-invasive or low-invasive samples like dry blood spots, saliva or urine.
Once we know what to look for we can tailor quantitative methods using liquid based separations like nano liquid chromatography and super critical fluid chromatography connected to tandem mass spectrometry for detection. Preferably we use stable isotope labelled internal standards or global labelling techniques for absolute quantitative analysis.