In search of disease-associated genes
Within a few weeks, researchers from the University Hospital Essen have published the findings of studies aimed at revealing disease-causing gene variants in the renowned journal Nature Genetics. Under the direction of Professor Dagmar Wieczorek and Professor Dietmar Lohmann from the Institute of Human Genetics, researchers have identified mutations in two genes, POLR1C and POLR1D, that cause the heritable Treacher Collins syndrome, characterised by facial anomalies. This finding confirms the suggestion that Treacher Collins syndrome is genetically heterogeneous, an insight important for genetic counselling. Professor Wieczorek also participated in a project which demonstrated that mutations in two other genes, GRIN2A and GRIN2B, are responsible for intellectual disability, behavioural anomalies, and idiopathic epilepsy. This finding opens up new opportunities for diagnosis. The incidence of mutations in these genes is 0.5% to 1%. Professor Johannes Hebebrand from the Department of Psychiatry and Psychotherapy and other colleagues from Essen contributed to one of the most comprehensive molecular genetic studies to date. The study, which involved nearly 250,000 subjects, found 18 new gene variants that influence body mass and thus obesity-associated diseases.

Blood cells: the good and the bad
The so-called B lymphocytes, white blood cells, play a central role in the immune defence against infections by generating antibodies. Professor Ralf Küppers and his team from the Institute of Cell Biology have shown that the immune system comprises several distinct populations of memory B cells that contribute to comprehensive and 
efficient immune protection. These findings contribute to our understanding of the development of immunologic disorders such as immune deficiency and autoimmunity. If B lymphocytes transform into cancer cells, they cause lymphoma and leukaemia. Investigating the development of the common Hodgkin lymphoma, Professor Küppers and his group haveidentified a new cancer-related gene (called A20) that plays an important role in this transformation process. These findings could contribute to the development of a more specific therapy for this type of cancer.

DFG funds myocardial infarction research
Myocardial infarction damages the heart because of an interruption in blood flow. However, the sudden restoration of blood flow can aggravate the aftermath of the heart attack. What exactly happens during reperfusion is the research focus of Professor Gerd Heusch, Director of the Institute of Pathophysiology. The German Research Foundation (DFG) has provided more than 800,000 euros in funding for his studies on postconditioning and on the underlying mechanisms and targeted manipulation of reperfusion.

New therapeutic avenues in stroke therapy …
Treating neurological diseases with medication is difficult because most drugs have only limited access to the brain. A breakthrough achieved by Dr. Ayman El Ali and Professor Dirk Hermann from the Department of Neurology has shown that a special protein, apolipoprotein E, regulates certain carrier proteins that in turn limit the passage of pharmacological compounds into the brain. This blockade can be overcome by deactivating a receptor for apolipoprotein E. These findings may have far-reaching consequences for therapeutic research by allowing better delivery of drugs to the brain and thus more effective treatment of diseases such as stroke.

… therapy of chronic viral infections …
Cytotoxic T lymphocytes (CTLs) are the main weapon used by the immune system to fight 
viruses. However, these cells can turn against 
the body’s own naturally existing molecules and thereby cause autoimmunity. To prevent overshooting of the CTL response during viral infection, CTLs are kept in check by so-called regulatory 
T cells (Tregs). Some viruses use this mechanism by triggering the expansion of Tregs and thus down-regulating the immune response directed against them. Professor Ulf Dittmer and colleagues from the Institute of Virology have demonstrated that switching off the Tregs for short periods can boost the antiviral immune response, making it more efficient and vigorous. In the future, the use of this strategy may make it possible to cure chronic viral infections such as HIV or hepatitis without the risk of triggering autoimmunity.

…and a novel pathophysiological mechanism

in inflammatory bowel disease Approximately 100,000 patients in Germany have ulcerative pancolitis, a severe subphenotype of inflammatory bowel disease. Professor Elke Cario and her group from the Department of Gastroenterology and Hepatology, in collaboration with Harvard Medical School, Boston, and UT Southwestern Medical Center, Dallas, have shown that bacterial structures can promote intestinal wound healing through increased production of a specific goblet cell-derived factor. In ulcerative pancolitis, a genetic immune defect may impair the ability of goblet cells to recognise bacteria, an impairment that reduces the synthesis of this factor. Mucosal wounds thus persist, and patients experience chronic bloody diarrhoea. Supplementation of the goblet cell–derived factor ameliorates colitis in mice. In the future, these results could offer a novel therapeutic approach for patients with pancolitis.