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Measuring Proteins, the Building Blocks of Our Bodies

Magnus Wetterhall
Department of Chemistry
Uppsala University
March 2002

The human body is a fascinating wonder in which billions of processes are constantly occurring. Proteins play an important role in all of these processes. As an analytical chemist, I am studying the protein content of various body fluids, such as blood or saliva, in order to understand and find early signs of disease and to investigate factors influencing communication, regulation and growth in healthy human cells. This work has implications in medicine, biology and chemistry.

All human cells contain a genome, which is the genetic information inherited from our parents. The genome is the cell blueprint, like the construction design for a house. The actual house is built out of proteins, "the building blocks of our bodies". Proteins are responsible for such diverse things as building our muscles and skin, digestion of food, cell growth and human emotions. There is a protein involved in almost any process one can imagine. Our bodies are constantly producing proteins. Sometimes malfunctions in the production process lead to new or changed proteins. In most cases, this has little or no effect in our bodies. However, in rare occasions, the changed protein leads to a better function in the body, commonly known as evolution. And in some unfortunate cases, a changed protein leads to a disease, such as Alzheimer's disease or Parkinson's disease.

In my research I am looking at the protein content in various body fluids including blood, urine, saliva and cerebrospinal fluid (the fluid surrounding the brain). These body fluids contain an enormous number of different proteins as well as other substances. Proteins are complex molecules and in order to identify them correctly one must often break them down into smaller fragments, called peptides. Each protein consists of many peptides, which are often specific for just that protein. For instance, the analysis of cerebrospinal fluid can be compared to taking your favorite book and mixing up all the words into a gigantic bowl of alphabet soup. One must first pick out each word and create sentences, paragraphs and chapters. Each sentence, paragraph and chapter must be arranged correctly in order for the story to read well.

Why measure the content of proteins and peptides in human body fluids? Well, as mentioned before, proteins and peptides play an important role in almost every process in the body and can be the root of disease. The concentration of a protein might be increased or decreased, or new proteins might appear as a consequence of a certain disease. The study and comparison between patients suffering from a disease and healthy people might reveal the cause of the disease. It is important to understand why a certain disease occurs and in an early state identify the signs for that disease to efficiently treat it. Beyond the treatment of disease, there is great interest in how healthy cells function. Ultimately, researchers will understand the role of individual proteins and how they work together to regulate the body. Returning the analogy of a house, this could be compared to standing at the construction site of a building and studying where each piece goes and how they come together to support the house.

How is this analysis conducted in the lab? First the, peptides are "picked out" or separated from each other. The separation is performed in an extremely small tube of glass. Under the influence of a strong electrical field, the peptides will move through the tube at different speeds. This separation technique, which takes advantage of the differences in speed, is called capillary electrophoresis. Second, the identity and amount of each peptide must be determined. This is done with a mass spectrometer. The mass spectrometer measures each peptide's mass-to-charge ratio. From the information obtained by the mass spectrometer one can determine the structure and mass of each peptide.

The detected peptides are then matched against databases containing peptide sequences of known proteins (imagine comparing the fragments from the book we destroyed to a database of possible sentences). This is done to identify the peptides and the proteins from which they came. The database matching is tedious and time consuming and thus there is a great need for fast and powerful computers and reliable databases. After peptide and protein matching is completed, it is up to the analysts to find trends in the results. Based on these trends, they then develop theories about the role specific proteins may play in the body.

My own research focuses on improving methods for separating and detecting proteins. I have refined the ways to separate and transfer the peptides from the glass tube to the mass spectrometer. Medical, biological and chemical researchers are now using my methods.