Cancer and Cardiovascular Researchers Discover Disease Gene for Cardiac Arrhythmia Disorder

Cancer and cardiovascular researchers at the Max  Delbrück Center for Molecular Medicine (MDC) in Berlin-Buch have discovered a disease gene which, when altered (mutated), can cause cardiac arrhythmias. The gene, located on chromosome 12, contains the blueprint for the protein plakophilin 2, an important component of cell membrane complexes (desmosomes). Desmosomes are essential for normal heart development in that they connect heart cells with each other and sustain their functioning. Dr. Brenda Gerull and Professor Ludwig Thierfelder, both at the MDC and the Helios Clinic Berlin/Charité - University Medical Center Berlin, examined patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), a specific kind of myocardial disease.  The researchers found that in about 25 to 30 percent of the ARVC patients, the plakophilin 2 gene is mutated. However, it is not clear why symptoms vary greatly in severity among those carrying the mutated gene. While some patients develop a life-threatening illness, others hardly experience any discomfort at all. Even children and adolescents can be affected by cardiac arrhythmias if they have inherited the mutated gene. The cancer researchers at the MDC, Katja Grossmann and Professor Walter Birchmeier, had given the heart researchers a lead by demonstrating that the hearts of mice which lack plakophilin 2 literally break. The studies have been published online in Nature Genetics* (October 17, 2004) as well as in the Journal of Cell Biology (Vol. 167, Issue 1, October 11, 2004, pp. 149-160)*.

Second Research Project with Human Embryonic Stem Cells at MDC

For the second time within a few days, the Robert Koch Institute (RKI) in Berlin (Germany) has authorized the Max Delbrück Center for Molecular Medicine (MDC) in Berlin-Buch to conduct research on human embryonic stem cells. On Thursday, October 21, 2004, the RKI, the responsible regulatory authority, announced approval of a research project proposed by Dr. Iduna Fichtner. Her project had previously received a positive assessment by the Central Ethics Commission for Stem Cell Research (ZES). Just recently, on October 8, 2004, the RKI had granted Dr. Daniel Besser of the MDC permission to conduct research on human embryonic stem cells. Since December 2002, the RKI has granted a total of seven authorizations for research on human embryonic stem cells in Germany, two of which have gone to the MDC.

Victor J. Dzau from Duke University Awarded Max Delbrück Medal

Pioneer in the Treatment of Congestive Heart Failure and Hypertension

For his “outstanding contributions to research and therapy of cardiovascular diseases” Prof. Victor J. Dzau from Duke University in Durham/North Carolina (USA) has been awarded the Max-Delbrück Medal in a ceremony at the Charité University Medicine in Berlin/Germany on October 14, 2004. “When looking back at your scientific work, today we are spanning about 30 years of your in-depth analysis of key regulatory factors in the cardiovascular system”, Dr. Joachim-Friedrich Kapp from Schering AG said in his address.“ Dr. Dzau is a pioneer in the therapeutic management of congestive heart failure (CHF) and hypertension” he stressed and especially referred to the so-called ACE-blockers to treat CHF. In addition, Dr. Dzau has developed gene and, most recently, cell therapeutic approaches toward the treatment of cardiovascular diseases. One such treatment involves a gene therapeutic approach to ensure sustainable bypass surgery by “arming” the grafted veins in such a way that they are not blocked by artherosclerosis. This approach is being tested in two large multicenter clinical trials (Phase III) in the USA. Dr. Dzau is not only a basic researcher and medical doctor, but also an entrepreneur. At the end of the nineties, he founded two biotech companies in California (Clingenix and Corgentech). The latter coordinates those clinical trials on coronary bypass-surgery.

Research Project with Human Embryonic Stem Cells at MDC - Robert Koch Institute in Berlin Grants Permission

Cell biologist and stem cell researcher Dr. Daniel Besser of the Max Delbrück Center for Molecular Medicine (MDC) in Berlin-Buch has received authorization from the Robert Koch Institute (RKI) in Berlin to conduct research on human embryonic stem cells. As the responsible regulatory authority, the RKI made the announcement of the approval on October 8, 2004. Previously, the Central Ethics Commission for Stem Cell Research (ZES) had made a positive assessment of Dr. Besser´s research project. As a result, he was granted permission to import four stem cell lines from the United States for research purposes. In this basic research project, Dr. Besser will investigate the regulatory mechanisms and factors which keep embryonic stem cells in an undifferentiated state as well as how specific kinds of cells develop from them. The planned duration of the research project is five years. Since December 2002, the RKI has granted six authorizations in Germany for research on human embryonic stem cells.

Puzzle Piece for Cancer Development

Prof. Birchmeier`s Lab at the MDC detects Molecular Switch

A new molecular puzzle piece, which plays a crucial role in cancer development, has been detected by cell biologists from the Max Delbrueck Center for Molecular Medicine (MDC) Berlin Buch and the Max Planck Institute for Immunobiology in Freiburg in Germany. Because this novel protein is similar to a human oncogene product (BCL9), the researchers named it BCL9-2. It determines which of the two functions the protein beta-Catenin will perform in the cell. Beta–Catenin acts as a binding molecule and mediates cell-cell adhesion (lat. catena = chain), under specific conditions it turns into a gene regulator. This is the case when BCL9-2 drags beta-Catenin into the cell nucleus. There beta-Catenin binds to DNA and turns on genes, which are essential for organ development, but which can also cause cancer. A prerequisite for turning beta-Catenin into a gene regulator is a process, molecular biologists call “tyrosine phosphorylation”. This means, a phosphate group attaches to the amino acid tyrosine, which makes beta-Catenin prone to react with BCL9-2. The findings of Dr. Felix H. Brembeck and Prof. Walter Birchmeier (both MDC) have been published online on September 1, 2004 by “Genes and Development”* (www.genesdev.org)

Million Euro Award to Young Hungarian Scientist at the MDC Research on “Mobile Genetic Elements”- High biomedical Potential

For her research on mobile genetic elements the Hungarian scientist, Dr. Zsuzsanna Izsvák, from the Max Delbrück Center for Molecular Medicine (MDC) in Berlin-Buch/Germany, has been awarded the inaugural European Young Investigators Award (EURYI) in Stockholm. The grant of about one million Euros allows her to set up a research group of her own over a period of five years at the MDC. The award is comparable in size to the Nobel Prize. According to the EURYI-committee, Dr. Izsvák is a leader in the field of research on mobile genetic elements (transposons). Transposon research is expanding our understanding of host transposon interactions, including principal molecular processes involved in cellular responses to DNA damage in mammals. As natural DNA-delivery vehicles, transposons have high potential for biomedical applications and may open promising new possibilities for gene therapy. Also, the application of transposons could bring gene discovery in vertebrates to another level.

10.5 Million Euro-Grant to fight Kidney Diseases

Thomas Willnow from the MDC Coordinates European Renal Genome Project

The European Union (EU) is determined to fight diseases of the kidney, a major cause of morbidity and mortality in Europe that affects approximately 4.5 million people. The EU has granted 10.5 million Euros for research into the genetic causes of kidney diseases over the next four years. Prof. Thomas Willnow, from the Max Delbrueck Center for Molecular Medicine (MDC) Berlin-Buch, coordinates this interdisciplinary European Renal Genome Project with 18 research groups from research institutions, universities and university clinics in nine participating European countries*. Other participants in Berlin are the nephrologists Prof. Friedrich Luft (Charité University Medicine/Helios Klinikum Berlin, MDC), and Dr. Dominik Müller (Charité Children`s Hospital).

Prof. Walter Birchmeier new Scientific Director of the Max Delbrück Center

Cell biologist and cancer researcher Prof. Walter Birchmeier has become the acting Scientific Director of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch. As former deputy chairman of the MDC Executive Board he succeeds Prof. Detlev Ganten who has become Chairman of the Executive Board of the Charité University Clinic in Berlin. Prof. Birchmeier shall hold the office until a successor has been appointed.

Variations in the Genome

Genes and their variations (mutations) can make one person more susceptible to disease than another. But how can scientists and physicians tell if a certain variation in the sequence of DNA really plays a role in the onset of disease? The human genome and genomes of various modell organisms now allow scientists to pursue this question more systematically. Dr. Heike Zimdahl and Dr. Norbert Hübner from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch have taken the first step towards recognizing those functionally important sequence variants. Together with the German MWG Biotech AG (Ebersberg near Munich) and scientists from the USA and Great Britain, they compared so-called complementary DNAs (cDNAs) of three different rat strains with the standard genome of the rat. As a result, they detected more than 12,000 variants. Using these results, they designed a map which, in their view, represents a valuable tool for comparative genome analysis and should help identify biomedically important genes. Their work has now been published in the renowned journal Science

Sleeping Beauty and DNA-Repair

Everyday DNA, the molecule of life is subjected to damages caused by viruses, bacteria, radiation, transposable DNA elements, and by events during the replication process. Luckily, these spontaneous changes or recombinations of DNA (mutations) are temporary in most cases and do not result in disease. Indeed, in the majority of cases, the cell machinery can immediately correct DNA damage - a critical point as the stability of DNA is of vital importance to the health of the individual. However, this process of DNA repair in mammals, and thus in humans, is not yet clearly understood. Now, for the first time, Dr. Zsuzsanna Izsvák and Dr. Zoltán Ivics, scientists from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch have been able to investigate the contribution of cellular pathways to the repair of transposition-induced DNA damage in mammalian cells. Until now, such research was impossible due to the lack of active DNA transposons in vertebrate species. The findings shed new light on the understanding of this vital mechanism. They are published in the latest issue in the renowned journal Molecular Cell* (Vol. 13, Nr. 2, pp. 279-290. 2004).