Press releases

Astrophysicists from Goethe-University Frankfurt have found a simple formula for the maximum mass of a rotating neutron star and hence answered a question that had been open for decades. A young women did the analysis during her bachelor thesis.

Neutron stars are the most extreme and fascinating objects known to exist in our universe: Such a star has a mass that is up to twice that of the sun but a radius of only a dozen kilometres: hence it has an enormous density, thousands of billions of times that of the densest element on Earth. An important property of neutron stars, distinguishing them from normal stars, is that their mass cannot grow without bound. Indeed, if a nonrotating star increases its mass, also its density will increase. Normally this will lead to a new equilibrium and the star can live stably in this state for thousands of years. This process, however, cannot repeat indefinitely and the accreting star will reach a mass above which no physical pressure will prevent it from collapsing to a black hole. The critical mass when this happens is called the "maximum mass" and represents an upper limit to the mass that a nonrotating neutron star can be.

However, once the maximum mass is reached, the star also has an alternative to the collapse: it can rotate. A rotating star, in fact, can support a mass larger than if it was nonrotating, simply because the additional centrifugal force can help balance the gravitational force. Also in this case, however, the star cannot be arbitrarily massive because an increase in mass must be accompanied by an increase in rotation and there is a limit to how fast a star can rotate before breaking apart. Hence, for any neutron star there is an absolute maximum mass and is given by the largest mass of the fastest-spinning model.

Determining this value from first principles is difficult because it depends on the equation of state of the matter composing the star and this is still essentially unknown. Because of this, the determination of the maximum rotating mass of a neutron star has been an unsolved problem for decades. This has changed with a recent work published on Monthly Notices of the Royal Astronomical Society, where it has been found that it is indeed possible to predict the maximum mass a rapidly rotating neutron star can attain by simply considering what is maximum mass of corresponding the nonrotating configuration.

"It is quite remarkable that a system as complex as a rotating neutron star can be described by such a simple relation", declares Prof. Luciano Rezzolla, one of the authors of the publication and Chair of Theoretical Astrophysics at the Goethe University in Frankfurt. "Surprisingly, we now know that even the fastest rotation can at most increase the maximum mass of 20% at most", remarks Rezzolla.

Although a very large number of stellar models have been computed to obtain this result, what was essential in this discovery was to look at this data in proper way. More specifically, it was necessary to realise that if represented with a proper normalisation, the data behaves in a universal manner, that is, in a way that is essentially independent of the equation of state.

"This result has always been in front of our eyes, but we needed to look at it from the right perspective to actually see it", says Cosima Breu, a Master student at the University of Frankfurt, who has performed the analysis of the data during her Bachelor thesis.

The universal behaviour found for the maximum mass is part of a larger class of universal relations found recently for neutron stars. Within this context, Breu and Rezzolla have also proposed an improved way to express the moment of inertia of these rotating stars in terms of their compactness. Once observations of the moment of inertia will be possible through the measurement of binary pulsars, the new method will allow us to measure the stellar radius with a precision of 10% or less.

This simple but powerful result opens the prospects for more universal relations to be found in rotating stars. "We hope to find more equally exciting results when studying the largely unexplored grounds of differentially rotating neutron stars", concludes Rezzolla.

Publication: Cosima Breu, Luciano Rezzolla: Maximum mass, moment of inertia and compactness of relativistic, in: Monthly Notices of the Royal Astronomical Society http://mnras.oxfordjournals.org/content/early/2016/03/14/mnras.stw575;doi: 10.1093/mnras/stw575

Interview with Cosima Breu und Luciano Rezzolla on Goethe-Uni online (in German): http://tinygu.de/Neutronensterne

Images for download: www.uni-frankfurt.de/60794123

Contact: Prof. Luciano Rezzolla, Institute for Theoretical Physics, Goethe University Frankfurt, Tel,: + 49 69 798 47871, rezzolla@th.physik.uni-frankfurt.de.

FRANKFURT.The number of children in Europe and the USA with type 1 diabetes is growing by four percent each year. A group of European researchers has now joined forces under the leadership of the Goethe University, with the goal of sparing affected people from lifelong insulin therapy. They plan to develop three-dimensional cellular structures of insulin-producing cells (organoids) in the laboratory and to work with pharmaceutical industry partners to develop a process for their mass production. The European Union is providing over five million Euro over the next four years to support the project. The first clinical studies on transplantation of organoids are planned after that.

Patients with type 1 diabetes are unable to produce insulin due to a genetic defect or an autoimmune disorder. They could be cured by transplanting a functional pancreas, but there are not nearly enough donor organs available. This is why researchers had the idea of growing intact insulin-producing cells from donor organs in the laboratory to form organoids, which they would then transplant into the pancreas of diabetes patients. "The method has already been shown to work in mice", explains Dr Francesco Pampaloni, who coordinated the first project together with Prof. Ernst Stelzer at the Buchmann Institute for Molecular Life Sciences at the Goethe University.

Researchers have only recently discovered how to produce organoids. Adult stem cells, which develop into cells for wound healing or tissue regeneration in the body, are the starting point. These cells can be grown in the laboratory through cell division and then allowed to differentiate into the desired cell type. The key is now to embed them in a matrix so that they grow into three-dimensional structures. The organoids are typically spherical, hollow on the inside and have a diameter of approx. 20 micrometres – about half as thick as the diameter of a human hair – to hundreds of micrometres. "If the structure were compact, then there would be a risk of the inner cells dying off after transplantation because they wouldn't be supplied by the host organ's cellular tissue", Pampaloni explains.

The task of the Frankfurt group under Stelzer and Pampaloni is to control the growth and differentiation of the filigree organoids under a microscope. To do so, they use a light microscopy method developed by Stelzer with which the growth of biological objects can be followed cell for cell in three dimensions. The project is called LSFM4Life, because light sheet fluorescence microscopy (LSFM) plays a key role in the project.

The Frankfurt group is also responsible for developing quality assurance protocols, because of the cooperation with industrial partners in Germany, France, the Netherlands and Switzerland, the original goal of the project is the large-scale production of organoids in accordance with good manufacturing practices for pharmaceuticals. Two research groups in Cambridge specialise in isolating insulin-producing cells from donor organs and growing organoids, while a group of clinicians in Milan is developing methods for transplanting organoids.

As is the case for all organ transplants, care will have to be taken with organoids as well so that rejection responses by the recipient's immune system are avoided. However, over time the researchers plan to build cell banks from which immunologically compatible cell types can be selected for every recipient.

Video: https://youtu.be/L3xjCEBHYZg

Caption: Mouse Pancreas Organoid imaged with a Digitally Scanned Light Sheet-based Fluorescence Microscope (LSFM, mDSLM). Left: actin cytoskeleton (staining Phalloidin-Alexa488). Right: cell nuclei (staining Draq5). Illumination objective lens Carl Zeiss Epiplan Neofluar 2.5x, NA 0.05. Detection objective lens Carl Zeiss W N-Achroplan 10x, NA 0.3. Imaging and visualization by Francesco Pampaloni, Goethe University Frankfurt, BMLS. Pancreas organoids from Meritxell Huch and Christopher Hindley, Gurdon Institute, Cambridge, UK

Information: Dr. Francesco Pampaloni, Buchmann Institute for Molecular Life Sciences, Campus Riedberg, Tel,: (069) 798 42544, francesco.pampaloni@physikalischebiologie.de

http://lsfm4life.eu

The Young Researcher Prizewinner is studying the role of RNAs in regulating cellular processes and investigating how this knowledge can be used for treating cancer and regenerating organs.

FRANKFURT am MAIN. Today, Dr. Claus-Dieter Kuhn from Bayreuth University will be awarded the €60,000 Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers for 2016. Kuhn, a biochemist and structural biologist, is being honored for his research into the leading role of RNAs in the cell. RNAs were long thought to only be the "executive" of the gene copying machinery. Yet they are the ones that really "pull the strings" in the cell. Some RNAs function as molecular switches, pushing development in one direction or another. Others flag messenger RNAs (mRNAs) for elimination, thereby controlling how many mRNAs are transcribed into proteins. Yet others dispose of themselves if they do not meet the cell's quality specifications. Kuhn has worked on various aspects of these processes, showing how RNAs, together with certain proteins, master these tasks and he has elucidated the properties that they exhibit for the purpose. The Scientific Council of the Paul Ehrlich Foundation acknowledges that Kuhn's work has advanced RNA research and has improved the prospects of harnessing RNAs for therapeutic purposes. The Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers will be presented by Professor Harald zur Hausen in the Paulskirche, Frankfurt.

Kuhn's work ties in with the observation that every cell contains hundreds of thousands of RNAs that are not translated into proteins and yet are not simply waste. For a long time scientists could see no rhyme or reason in this. Nor could they understand why many living creatures – for instance chimpanzees and humans – have a virtually identical genetic makeup and yet show significant differences in their appearance and skills. We now know that non-coding RNAs play an important role in the differentiation process. Kuhn has analyzed this issue at various levels. Among his early achievements are molecular snapshots of the enzyme RNA polymerase I. This enzyme produces the ribosomal RNAs that are part of the ribosomes, the protein factories. From these snapshots it was possible to derive a model of the enzyme. Kuhn later showed how transfer RNAs, which supply amino acids for protein biosynthesis, brand themselves if they are defective. They employ a special signature to achieve this. Kuhn has also been instrumental in elucidating the structure of a protein termed Argonaute 2. This protein modulates protein biosynthesis by working together with short RNAs to cleave complementary mRNAs. Kuhn is now working on RNAs that turn genes on and off. These findings could well advance our medical state of the art.

Short biography of Dr. Claus-Dieter Kuhn

Claus-Dieter Kuhn, age 37, was born in Mutlangen (close to Stuttgart, Germany), began studying biochemistry in Regensburg and completed his Master's degree in chemistry at the University of Stockholm in Sweden. For his PhD work Kuhn moved to the Gene Center of the University of Munich (LMU) in Germany. From Munich he went to Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, USA. He interrupted his stay there in 2009 to spend a year working for Proteros Biostructures GmbH, a company based in Munich. In 2010 Kuhn returned to Cold Spring Harbor Laboratory. Since fall 2014 he is at Bayreuth University where he heads a Junior Research Group at the Research Center for Bio-Macromolecules. His work is supported by the Elite Network of Bavaria. Claus-Dieter Kuhn has won numerous prizes, among them a gifted student scholarship of the Wilhelm Narr Foundation and a Kekulé Fellowship from the German Chemical Industry Fund (FCI). He was a fellow of the Jane Coffin Childs Memorial Fund for Medical Research based at Yale University. Moreover, he participated in two graduate programs and was awarded the Römer Prize of the University of Munich.

Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers

The Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers, awarded for the first time in 2006, is conferred once a year by the Paul Ehrlich Foundation on a young investigator working in Germany for his or her outstanding achievements in the field of biomedical research. The prize money must be used for research purposes. University faculty members and leading scientists at German research institutions are eligible for nomination. The selection of the prizewinner is made by the Scientific Council on a proposal by the eight-person selection committee.

The Paul Ehrlich Foundation

The Paul Ehrlich Foundation is a legally dependent foundation which is managed in a fiduciary capacity by the Association of Friends and Sponsors of the Goethe University, Frankfurt. The Honorary Chairman of the Foundation, which was established by Hedwig Ehrlich in 1929, is the German Federal President, who also appoints the elected members of the Scientific Council and the Board of Trustees. The Chairman of the Scientific Council is Professor Harald zur Hausen, and the Chair of the Board of Trustees is Professor Dr. Jochen Maas, Head of Research and Development and Member of the Management Board, Sanofi-Aventis Deutschland GmbH. Professor Wilhelm Bender, in his function as Chair of the Association of Friends and Sponsors of the Goethe University, is Member of the Scientific Council. The President of the Goethe University is at the same time a member of the Board of Trustees.

Further information

You can obtain selected publications, the list of publications and a photograph of the prizewinner from the Press Office of the Paul Ehrlich Foundation, c/o Dr. Hildegard Kaulen, phone: +49 (0) 6122/52718, email: h.k@kaulen.wi.shuttle.de and at www.paul-ehrlich-stiftung.de.

Emmanuelle Charpentier and Jennifer A. Doudna have developed the bacterial gene cutter CRISPR-Cas9 in such a way that specific DNA sequences can be targeted and cleaved. The technology is opening up completely new perspectives for research.

FRANKFURT am MAIN. Emmanuelle Charpentier from France and Jennifer A. Doudna from the USA are today being awarded the Paul Ehrlich and Ludwig Darmstaedter Prize for 2016 in the Paulskirche in Frankfurt. The two scientists are being honored for their pioneering work in the development of the programmable gene editing tool CRISPR-Cas9. "With this precision tool genes can be modified easily and precisely," wrote the Scientific Council of the Paul Ehrlich Foundation in explaining its decision. "The prizewinners recognized and identified this potential and demonstrated the technology's far-reaching applications." In the shortest time, CRISPR-Cas9 has become one of the most sought-after tools in molecular biology research, the Scientific Council continues. CRISPR-Cas9 is so easy to use that genome editing, which only a few years ago was extremely complicated, has become a routine procedure. The Council also paid tribute to the fact that Doudna and Charpentier were among the first to call for debate on the ethical issues because CRISPR-Cas9 can also be used to edit and engineer the germline. Charpentier is Director at the Max Planck Institute of Infection Biology in Berlin and Professor at Umeå University in Sweden. Doudna is the Li Ka Shing Chancellor’s Professor at the University of California, Berkeley. The Paul Ehrlich and Ludwig Darmstaedter Prize is among the most prestigious international awards granted in the Federal Republic of Germany in the field of medicine. The Prize will be presented by Professor Harald zur Hausen, Chairman of the Scientific Council.

Charpentier and Doudna were the first to demonstrate that CRISPR-Cas9, developed by bacteria as a defense against bacteriophages, can be used to target and cleave any DNA sequence.  The gene cutter is programmed and controlled by a guide RNA. One of the prizewinners' achievements is that they have made the gene cutter easier and more user-friendly. Experiments in numerous laboratories have quickly shown that this simplified form works not only in the test tube but also in living cells and in many organisms. The DNA is edited and engineered in repairing double strand breaks.  This makes it possible to replace or alter genes or knock them out of action. There is strong evidence that CRISPR-Cas9 will help cure hereditary diseases, eradicate dangerous pathogens, and breed better plants.

The two prizewinners' pioneering publication in 2012 - following the breakthrough finding by Charpentier in 2011 of the CRISPR-Cas9 system - unleashed a veritable wave of CRISPR-Cas9 research. Since then, thousands of publications have appeared that reveal its true potential and describe further details and potential developments of the CRISPR technology. "This technology is changing both fundamental research and clinical and commercial opportunities in biology," says Doudna. "That's very exciting." Charpentier says: "I think that CRISPR-Cas9 has the potential to really change the biotechnology and the medical landscapes."

At the ethics summit held in Washington in December 2015, both scientists spoke out against editing of the human germline for clinical applications at this time. In the concluding statement, which Doudna as one of the organizers also signed, germline editing is deemed to be "irresponsible" unless and until the relevant ethical and safety issues have been resolved. The document also declares that norms concerning acceptable uses should be established by the international community.  The summit did not call for a moratorium but rather for intensification of research within the legal and ethical boundaries.

Short biography of Professor Dr. Emmanuelle Charpentier

Emmanuelle Charpentier (age 47) was born in Juvisy-sur-Orge, France, in 1968. She studied microbiology, genetics and biochemistry in Paris and completed her doctorate at the Institut Pasteur. After working in New York and Memphis, notably at the Rockefeller University, Charpentier moved to the University of Vienna in 2002 and to Umeå University in 2009, where she is still Visiting Professor. Charpentier came to Germany in 2013 on a Humboldt Professorship. She first headed a Department at the Helmholtz Center for Infection Research in Braunschweig and was full Professor at the Hannover Medical School. She was appointed Director at the Max Planck Institute for Infection Biology in Berlin in October 2015. Charpentier has been awarded well over two dozen different prizes, including the three million dollar Breakthrough Prize in Life Sciences, the Leibniz Prize of the German Research Foundation and an honorary doctorate of the University of Louvain. She is a member of various science academies and associations, including Germany's Academy of Sciences Leopoldina and elected foreign member of the Royal Swedish Academy of Sciences. She co-founded CRISPR Therapeutics in 2014 and ERS Genomics in 2013.

Short biography of Professor Dr. Jennifer A. Doudna

Jennifer A. Doudna (age 52) was born in Washington, DC and grew up in Hilo, Hawaii. She studied chemistry at Pomona College in California and took her doctorate in biological chemistry and molecular chemistry at the Harvard University in 1989.  After her doctorate, Doudna moved to the University of Colorado. In 1994 she was appointed professor at Yale, and she has been a professor at the University of California, Berkeley, since 2002. At Berkeley she serves as Chair of the Chancellor's Advisory Committee on Biology. Doudna is also the Executive Director of the Innovative Genomics Initiative at UC Berkeley/UCSF. The co-prizewinner has been an investigator with the Howard Hughes Medical Institute since 1997. She has won numerous awards, including the three million dollar Breakthrough Prize in Life Sciences. Doudna is a member of various science academies and associations, including the National Academy of Sciences, the National Academy of Medicine, the National Academy of Inventors and the American Academy of Arts and Sciences. She is also a co-founder of Editas Medicine, Intellia Therapeutics and Caribou Biosciences.

The Paul Ehrlich and Ludwig Darmstaedter Prize

The Paul Ehrlich and Ludwig Darmstaedter Prize is traditionally awarded on Paul Ehrlich's birthday, March 14, in the Paulskirche, Frankfurt. It honors scientists who have made significant contributions in Paul Ehrlich's field of research, in particular immunology, cancer research, microbiology, and chemotherapy. The Prize, which has been awarded since 1952, is financed by the German Federal Ministry of Health, the German association of research-based pharmaceutical company vfa e.V. and specially earmarked donations from companies. The prizewinner is selected by the Scientific Council of the Paul Ehrlich Foundation.

The Paul Ehrlich Foundation

The Paul Ehrlich Foundation is a legally dependent foundation which is managed in a fiduciary capacity by the Association of Friends and Sponsors of the Goethe University, Frankfurt. The Honorary Chairman of the Foundation, which was established by Hedwig Ehrlich in 1929, is the German Federal President, who also appoints the elected members of the Scientific Council and the Board of Trustees. The Chairman of the Scientific Council is Professor Harald zur Hausen, and the Chair of the Board of Trustees is Professor Dr. Jochen Maas, Head of Research and Development and Member of the Management Board, Sanofi-Aventis Deutschland GmbH. Professor Wilhelm Bender, in his function as Chair of the Association of Friends and Sponsors of the Goethe University, is Member of the Scientific Council. The President of the Goethe University is at the same time a member of the Board of Trustees.

Further information

You can obtain selected publications, the list of publications and a photograph of the laureates from the Press Office of the Paul Ehrlich Foundation, c/o Dr. Hildegard Kaulen, phone: +49 (0)6122/52718, email: h.k@kaulen.wi.shuttle.de and at www.paul-ehrlich-stiftung.de

New research co-led by the University of Kent has identified a first step in the design of a new generation of anti-cancer drugs that include an agent to inhibit resistance to their effectiveness. 

The research by a team led by Professor Martin Michaelis of Kent’s School of Biosciences, in conjunction with Professor Jindrich Cinatl of theGoethe-University, Frankfurt am Main, Germany, could pave the way for tailored combinations of drugs that would provide more effective treatment for patients suffering from therapy-resistant cancers.

Drug resistance is the major reason for the failure of anti-cancer therapies and patient deaths. Despite major improvements in cancer treatment in recent decades, cures are still mostly achieved by early cancer detection and local therapy using surgery and radiotherapy. Once cancer cells have spread throughout the body and formed metastases (secondary tumours), the prognosis remains grim with 5-year survival rates being below 20%.

Effective systemic drug therapies are needed therefore to improve the outcomes of patients diagnosed with metastatic disease. However, many cancers are characterised by intrinsic resistance, where there is no therapy response from the time of diagnosis, or acquired resistance, where there is an initial therapy response but cancer cells eventually become resistant.

Arguably, the most important resistance mechanism in cancer cells is the action of so-called ATP-binding cassette (ABC) transporters, drug pumps that act as a mechanism to move anti-cancer drugs from cancer cells. Of these, ABCB1 (also called multi-drug resistance gene 1 (MDR1) or P-glycoprotein) is the most relevant one. Previous attempts to target ABCB1 as part of anti-cancer therapies have failed.

A major reason for this is that ABCB1 is expressed at many sites in the body, particularly at tissue barriers such as the gastro-intestinal barrier and the blood brain barrier. This has meant in the past that agents that inhibited ABCB1 were not specific to the interaction of the desired anti-cancer drug with the ABCB1 on cancer cells but affected the body distribution of many different drugs and food constituents, resulting in toxic side-effects.

The new research demonstrates that certain inhibitors of ABCB1 specifically interfere with the ABCB1-mediated transport of certain anti-cancer drugs. This provides a first step towards the design of tailored combinations of anti-cancer drugs and ABCB1 inhibitors that specifically cause the accumulation of anti-cancer drugs in ABCB1-expressing cancer cells but do not affect the body distribution of other drugs or food constituents.

In addition to Professor Michaelis and Professor Cinatl and their laboratory members, the team included Dr Mark Wass (University of Kent), Professor Manfred Schubert-Zsilavecz (Goethe-University Frankfurt), Dr Taravat Ghafourian (University of Sussex), and Professor Michael Wiese (University of Bonn) and members of their research groups.

The research, entitled Substrate-specific effects of pirinixic acid derivatives on ABCB1-mediated drug transport, was published in Oncotarget. See here:

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=7345&author-preview=5o1

Informationen:

Prof. Dr. Jindrich Cinatl, Institut für Medizinische Virologie, Goethe-Universität Frankfurt; cinatl@em.uni-frankfurt.de; +49 69 6301 6409; Dr. Florian Rothweiler; f.rothweiler@kinderkrebsstiftung-frankfurt.de; +49 69 6786 6572.