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Archive - Jul 16, 2015

Innate Immune System and Iron Metabolism Work Together to Fight Off Pathogens; Functional IRP/IRE System Key to Denying Crucial Iron to Potential Invaders

Proteins responsible for controlling levels of iron in the body also play an important role in combatting infection, according to a study published online on July 16, 2015 in Cell Host & Microbe. The article is titled “Iron Regulatory Proteins Mediate Host Resistance to Salmonella Infection.” Humans, along with all living organisms, including pathogen, need iron to survive. Invading organisms try to highjack it from their hosts in order to thrive and multiply. Researchers at EMBL Heidelberg, and their colleagues, have now discovered that proteins responsible for helping the body maintain the correct levels of iron at a cellular level are also involved in helping to prevent this theft. These proteins form a system called IRP/IRE (iron regulatory protein/iron responsive element). “The work we’ve been doing has uncovered a connection between two very important functions that are typically seen as separate: the body’s innate immune system, and its iron metabolism,” explains Dr. Matthias Hentze, co-author of the paper and Director of EMBL. The research team analyzed how mice reacted to an infection by the Salmonella bacteria, depending on whether they had a functional IRP/IRE system or not. Mice lacking a functional IRP/IRE system from professional immune cells called macrophages did well as long as they were not infected, but when the Salmonella bacteria were introduced, the mice died. This showed that the iron regulatory system was crucial for the macrophages, the target-cells for this specific pathogen, to fight off the infection effectively. “Withholding iron from an invading pathogen is an innate defense against infection,“ explains Dr. Bruno Galy, former Staff Scientist at EMBL-Heidelberg and currently Group Leader at the German Cancer Research Centre (DKFZ).

Partial Structure of Key Protein (Oskar) for Development of Reproductive Cells Is Revealed in EMBL Heidelberg Studies

The structure of two parts of the Oskar protein, known to be essential for the development of reproductive cells, has been solved by scientists from EMBL Heidelberg in Germany. This advance, published online on July 16, 2015 in Cell Reports, has also enabled the research team to gather the first insights into how this poorly understood protein functions. The research was carried out with fruit flies, but has implications for other animals, as many organisms, including humans, also possess part of the Oskar protein. Named after the main character from the Günter Grass novel “The Tin Drum,” who chose never to grow up, the Oskar protein is essential for development. Embryos that develop from fruit fly eggs lacking the normal amount of Oskar protein are unable to form germ cells – cells that allow reproduction – and so the resulting flies are sterile. Complete lack of the Oskar protein also prevents the embryo’s abdomen from forming normally which stunts its growth and causes such flies to die. In a healthy egg, the Oskar protein initiates the formation of what’s known as the germ plasm – a gathering of proteins and RNAs within the cytoplasm, which then goes on to form a new germ cell. Germ plasm normally forms in a particular position within the egg, but if Oskar is artificially moved elsewhere, the germ plasm will form in the new location. Co-author of the paper, Dr. Anne Ephrussi said: “While we’ve known Oskar’s genetic role in development for some time, we’ve not known the mechanism by which this takes place. Solving the structure has enabled us to start to see how the different parts of the protein function at a molecular level, which could help us to understand more about this stage of development in a wide range of organisms.”

Reducing High Levels of Ceramides May Improve Insulin Sensitivity and Provide an Effective Treatment for Type 2 Diabetes and Nonalcoholic Fatty Liver Disease

Reducing high concentrations of a fatty molecule that is commonly found in people with diabetes and nonalcoholic fatty liver disease rapidly improves insulin sensitivity, Univeristy of Texas (UT) Southwestern Medical Center diabetes researchers have found. Insulin is a crucial hormone that helps the body convert sugar into energy, absorb nutrients, and reduce the storage of sugars as fat. Poor insulin sensitivity reduces the effectiveness of these processes and results in diabetes and fatty liver disease. UT Southwestern researchers showed that introducing an enzyme called ceramidase in diabetic mice returned their insulin sensitivity to normal. “Lowering ceramides (image) may also make people more insulin-sensitive,” said study senior author Dr. Philipp Scherer, Director of the Touchstone Center for Diabetes Research at UT Southwestern. “Our findings suggest a new means to potentially treat Type 2 diabetes and nonalcoholic fatty liver disease.” Though no such therapy currently exists, Dr. Scherer said a drug form of the enzyme ceramidase likely could be developed. The findings were published online on July 16, 2015 in the journal Cell Metabolism. The article is titled “Targeted Induction of Ceramide Degradation Leads to Improved Systemic Metabolism and Reduced Hepatic Steatosis.” When more fatty acids are consumed than the body burns off, some excess fat is converted to ceramide. When too much ceramide builds up, the lipid interferes with insulin signaling, resulting in insulin resistance and possibly diabetes or nonalcoholic fatty liver disease. “It is a nasty lipid at times,” said Dr. Scherer, Professor of Internal Medicine and Cell Biology who holds the Gifford O. Touchstone, Jr. and Randolph G. Touchstone Distinguished Chair in Diabetes Research at UT Southwestern.

Improved Treatment for Vitiligo Skin Discoloration

According to a July 16, 2015 press release, a University of Texas (UT) Southwestern Medical Center dermatologist has improved a technique to transplant pigment cells that can repair the affected area of skin discoloration from vitiligo. Dr. Amit Pandya, Professor of Dermatology at UT Southwestern, refined and enhanced this technique, which uses a less painful process, rather than cutting into the skin, to obtain the cells needed for the transplant. The cells are harvested from a painless blister raised on the skin, then transferred to the area of involvement to replace the missing pigment cells and restore the individual’s natural skin color. UT Southwestern is the only center in the United States to use this technique and one of only two centers to perform this type of cell transplant surgery, called non-cultured epidermal suspension (NCES) grafting, cellular grafting, or melanocyte keratinocyte transplant procedure (MKTP). “This provides new hope for patients with vitiligo,” said Dr. Pandya, who holds the Dr. J.B. Shelmire Professorship in Dermatology. “The unique aspect of our procedure, which no one else in the world is doing, is the formation of blisters as the source of donor cells combined with laser surgery to prepare the grafted areas. The older method of cutting the skin leaves a scar.” Dr. Pandya, the only full-time pigmentary disorders specialist in Texas, has spent more than a decade treating vitiligo patients in the Pigmentation Disorders Clinic at UT Southwestern. Vitiligo affects about 2 million people in the United States. Vitiligo occurs when the body is triggered to look at melanocytes, cells which give color to the skin, as foreign or abnormal. With vitiligo, the body’s own immune system starts attacking those cells, which is why it’s considered an autoimmune disease.