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Source: Julich research center German research Foundation (DFG) supports a new research group to protein family SLC26, with around four million euros

Jülich, 30. April 2020 – SLC26 refers to a family of transport proteins, which is involved in numerous processes in the human body – for example, in the kidney and in the intestine. It is known that malfunction of these transporters can have serious health consequences. Why is this so, and how these protein machines under normal conditions, enable the organ function, the research is still at the beginning. A new research group under the leadership of the Philipps-University of Marburg will now analyse individual proteins of the family from the molecular to the organic layer and its structure, function and Regulation under the microscope. Long-term goal is to develop new treatment options for diseases such as hypertension, inflammatory bowel disease or cystic fibrosis are. The DFG is funding the project with around four million euros over a period of four years.

All of our cells and body fluids contain large amounts of dissolved, negatively charged particles called anions. Their concentration must be set very precisely so that there is no serious derailment of the body’s function. For example, the chloride, which we consume as part of the table salt, has to be absorbed into the body by the intestine and excreted in sufficient amounts via the kidney. The anion is transported across the cell membrane. The SLC26 transporters, a family of proteins that are found in the membranes of the cells of the intestine and kidney, play a prominent role in the transport of anions. “This family is responsible for vital transport processes in the human body. This important role has been scientifically documented in detail, ”says Prof. Dr. Dominik Oliver, spokesman for the new research group. “However, what has so far been neglected in research is the precise analysis of the SLC26 proteins. Basically, we hardly know anything about the molecular functioning of the proteins or their integration into the cell. We are very pleased that we can now take these steps with the new research group and make an elementary contribution to understanding the proteins and the various associated clinical pictures, “says Oliver. The new research group brings together scientists from the Philipps University in Marburg Goethe University Frankfurt, the Max Planck Institute for Molecular Cell Biology and Genetics Dresden, the Research Center Jülich, the University of Rostock, the Heinrich Heine University Düsseldorf, the Hannover Medical School and the Charité – Universitätsmedizin Berlin. All members of FOR 5046 have many years of experience in research with SLC26 or similar transport proteins. What is special about the new research group is the first close networking of broad expertise – from molecular biophysics to disease-related clinical expertise. At the same time, the latest methods are applied to this special protein family for the first time, including computer-based simulation of molecular movements and the analysis of living cells from patient biopsies. The researchers in the research group “FOR 5046 – Integrative Analysis of Epithelial SLC26 Anion Transporters – from Molecular Structure to Pathophysiology” will jointly analyze the structure, function and regulation of selected SLC26 proteins: What three-dimensional structure do the proteins have? How does this structure enable dissolved particles to enter the cell? How do the proteins interlock, which interaction occurs? What role do proteins play in cell events? The researchers are devoting themselves to these and other questions. Dominik Oliver will focus on a few proteins from the SLC26 family, such as SLC26A3. This protein is mainly found in the cell membrane of the intestinal mucosa and is associated with congenital chloride diarrhea, a serious diarrhea. “We will use different technologies to map the molecular anatomy of the protein – among other things, we can measure the different conformations, i.e. the spatial arrangement of the protein, and the transitions between the different positions in real time,” says Oliver. In addition, targeted mutations are to be induced in SLC26A3 in order to be able to analyze their effects on organ function. So-called organoids, i.e. organ-like microstructures a few millimeters in size, are also used. For example, these are generated in the laboratory from human cells and largely reproduce the function, but also diseases of entire organs. “With these and other methods, we will be able to draw important conclusions about the structure, regulation and physiology of the SLC26 family,” said Oliver. In Marburg, the examinations are carried out at the Institute of Physiology and Pathophysiology at the Medical Faculty of the Philipps University. The institute conducts research in both basic and translational projects in the field of molecular cell and neurophysiology. Other current projects at the institute are devoted to the sensory cells of the inner ear or the regulation of another class of transport proteins, so-called ion channels. Further information: Institute for Biological Information Processes, Molecular and Cell Physiology (IBI-1) Contact: Prof. Christoph Fahlke Tel .: 02461 61-3016 Email: c.fahlke@fz-juelich.de

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