In an article in the latest issue of Molecular & Cellular Proteomics, Uppsala University researchers describe a technique that the journal regards as especially interesting.

Proteins build up the body's cells and tissues, and our knowledge of the human genome also entails that today's scientists are aware of all of the proteins that our body can produce. It is known that many morbid conditions can be linked to changes in proteins, so it is important to enhance our knowledge of what proteins bind to each other, how they work together, and how processes are impacted by various disturbances.

In 2006 Ola S?¶derberg and his colleagues at the Department of Genetics and Pathology devised a new technique, in situ PLA (in situ proximity ligation assay), that could detect communication between proteins in cells. These researchers have now refined the method and can now see how proteins undergo change inside a cell.

The method provides a better potential to truly understand how proteins function in the cell and can show what is wrong with a sick cell, as in cancer, for instance. The refined method has the potential to revolutionize cancer diagnostics, so there has been a great deal of interest in the method from the research community, says Ola S?¶derberg.

The technique is more sensitive and more reliable than other available techniques in molecular diagnostics, and it has already started to be sold by the Uppsala company Olink, so there are high hopes that it will soon be used in health care.

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In order to become a specialized organ, tissue, or neural cell, a stem cell needs to be pointed in the right direction, and that guidance is believed to be provided by a highly complex arrangement of genes. If researchers can isolate the specific genetic sequences that cause a stem cell to transform into a neural cell, the example that Kane used in his research, they can begin to develop medical treatments for common diseases like Parkinson's disease using specially programmed stem cells infected with the correct arrangement of genes to produce healthy neural cells.

Kane and his team developed a specialized stamping technique that can be used to quickly understand how different genetic sequences affect stem cell development. The stamp is covered with thousands of mircoscale prongs, similar to the surface of a LEGO?®. Those prongs imprint the surface of the corresponding slide, creating a microarray platform with thousands of individual cell-adhesive divots ” the perfect mircoscale Petri dishes. The master stamp can create thousands of stamped surfaces without the needs for a clean room or sophisticated machinery.

To develop the stem cell mixture added to the stamped surface, the researchers first created a stem cell library. Each stem cell within this library would overexpress a different genetic sequence. Cells from the library are then dropped onto the micropatterned surface, such that each divot contains only one type of cell. Those seeded populations then divide to form individual clonal populations of cells. A stamped surface the size of a microscope slide can contain 3,500 clonal cell populations. These populations can then be screened at the same time for researchers to determine which cells exhibit a desired behavior (i.e. the development of healthy neural cells). The researcher then immediately knows what DNA sequence is responsible for the observed behavior.

To exhibit the effectiveness of their technology, Kane and his group screened clonal populations of rat neural stem cells to identify a sequence that promoted neural stem cell proliferation.

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