Fine-tuning the toxins of the immune system
White blood cells called cytotoxic T cells (CTLs) play a crucial role in fighting disease; they identify other cells which are infected or damaged, then release toxic substances that destroy them. In recent years scientists have identified molecules within CTLs that help secrete the toxins. But little is known about the contrary process, which keeps levels of the substances low and prevents their release at the wrong time. A new study from the laboratories of Armin Rehm, Uta Höpken, and Bernd Dörken at the MDC/Charité University Hospital, along with several collaborating groups, has now exposed a new mechanism that helps cells control the toxins. One finding from the study, which appeared in the August 3 edition of the Journal of Clinical Investigation, is a potential link between the hormone estrogen and the way the immune system responds to cancer.
Lifting the cover on stem cells and cancer
Frank Rosenbauer's lab at the MDC and their international collaborators have discovered a new mechanism that controls whether stem cells stay generic or differentiate in specific ways. A chemical code called methylation, which cells use to control large numbers of genes, also determines the fate of some stem cells. The work, published in the October 4, 2009, online issue of Nature Genetics, should help researchers understand why blood cells sometimes deviate from normal developmental routes. It may also lead to new approaches in the treatment of leukemia and other types of cancer.
Decision at the crossroads
As an embryo develops, its neurons extend long, trunk-like axons that establish contact with other cells. Along the way, the axons split into branches so that they can transmit information to multiple cells. Little is known about this process of forking, but in the Sept. 29 issue of PNAS, Fritz Rathjen's laboratory at the MDC reports the discovery of a new protein signal that triggers the axons of some nerve cells to split.
A frame-by-frame view of animal development
Nikolaus Rajewsky's lab at the MDC, collaborating with Fabio Piano at New York University, has found a way to capture thousands of embryos of the worm C. elegans, one of biology's most important model organisms, at precise stages of development. The method, which is described in the Sept. 6 on-line issue of Nature Methods, will allow scientists to "microdissect" molecular events in the growth of this tiny roundworm. Since C. elegans and humans are related through evolution, this work has led to important insights into the function of genes in our own species as well.
The genetic engineering of the future
A step forward for transposons as tools for genetics and therapies
The labs of Zsuzsanna Izsvák and Zoltán Ivics at the MDC have been working to transform molecules called transposons – also known as "jumping genes" – into new tools for research and therapies. In a recent online edition of Nature Genetics, the researchers announce that they have made major steps toward this goal through the development of a "hyperactive" version of a transposon called Sleeping Beauty.
A bone balancing act
Achim Leutz's laboratory at the MDC has discovered that the form of a molecule called C/EBP-beta produced by cells determines whether they create new bone or break it down. This balance is crucial to maintaining bone structure. The finding may help to explain how the process becomes disregulated in a number of serious bone diseases.
A red thread through the epithelia:
Atopic dermatitis linked to chromosome 11
Researchers at the MDC, the Charité University Hospital, the Christian-Albrecht University of Kiel, and several other collaborating laboratories have connected a region of human chromosome 11 to an increased risk of developing atopic dermatits, or eczema, a common symptom of allergies. The finding is an important step toward learning why the symptoms appear and hints at a connection between dermatitis and other diseases.
Investigating the Development of Mechanosensitivity
Researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have gained crucial insight into how mechanosensitivity arises. By measuring electrical impulses in the sensory neurons of mice, the neurobiologists and pain researchers Dr. Stefan G. Lechner and Professor Gary Lewin were able to directly elucidate, for the first time, the emergence of mechanosensitivity. At the same time they were able to show that neurons develop their sensitivity to touch and pain during different developmental phases but always coincidentally with the growth of the neuronal pathways. (EMBO Journal, 2009, doi:10.1038/emboj.2009.73).
Charging the batteries of immunity
White blood cells use highly reactive forms of oxygen as one means of fighting bacteria and other disease-causing organisms. These superoxides are manufactured in cellular compartments called phagosomes; making them requires keeping the phagosomes "charged." The laboratories of Ralph Kettritz, Maik Gollasch, Friedrich Luft, and their collaborators have now made an important discovery about how cells maintain the charge.
New Control System of the Body Discovered
Important Modulator of Immune Cell Entry into the Brain
Researchers in Berlin, Germany have ameliorated inflammation of the brain in mice caused by immune cells. A receptor they discovered on the surface of T cells in the central nervous system (CNS) plays the key role. The researchers showed that this bradykinin receptor 1 (B1) controls the infiltration of immune cells into the CNS. When they activated B1 in mice with encephalitis, they were able to slow down the crossing of the immune cells through the blood-brain-barrier into the CNS. As a result, the inflammation markedly decreased. The work by Dr. Ulf Schulze-Topphoff, Prof. Orhan Aktas, and Professor Frauke Zipp (Cecilie Vogt-Clinic, Charité – Universitätsmedizin Berlin, Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and NeuroCure Research Center) together with researchers in Canada and the USA may unveil a new target for the treatment of chronic inflammatory diseases such as multiple sclerosis (MS) (Nature Medicine, doi 10.1038/nm.1980).
MDC Researchers Prevent Virus Induced Myocarditis
First Studies in Mice
Life-threatening cardiac arrhythmia can be a consequence of myocarditis – an inflammation of the cardiac muscle that can be caused by the Coxsackievirus. In mice, Dr. Yu Shi, Chen Chen, and Professor Michael Gotthardt of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now abolished the infection by blocking the receptor which is required for virus entry. “We did not detect a single cardiomyocyte that was infected by the virus. Inflammation of the heart muscle associated with this virus infection did not develop,” Dr. Shi said.
Illuminating metastases
A new marker for metastasis in colorectal cancer
Researchers at the MDC and the Charité have discovered that the presence of a protein indicates whether some colorectal cancers will lead to metastases. The groups are working to turn the discovery into a tool for diagnosis and better therapies. Their findings may also shed light on a current debate about why metastases happen.