Stefan Knapp elected as member to the European scientific organisation for molecular biology, EMBO
FRANKFURT. Not everyone person who has a “cancer gene” will inevitably develop this disease in their lifetime. Thanks to a new area of research called epigenetics, we now know that many genes are only read under certain circumstances. Prof. Stefan Knapp from the Institute of Pharmaceutical Chemistry and Buchmann Institute of Molecular Life Sciences at the Goethe University not only researches the underlying mechanisms, he also developed small molecules that inhibit the derailment of gene expression in cancer. Now he has been elected as one of 62 new members in the European scientific organization for molecular biology, EMBO, joining a group of more than 1800 of the best researchers in Europe and around the world.
“I am delighted that I have been elected to the EMBO society and I am looking forward working with this group of outstanding scientists to advance research, exchange new ideas, and promote science in society”, says Stefan Knapp.
Prof Knapp has made seminal contributions to the elucidation of structural mechanisms of the regulation of proteins that play key roles in signal transduction. This in turn led to a detailed description of protein family specific regulatory mechanisms and the elucidation of substrate recognition processes. Based on these findings, he developed a large array of new small molecule inhibitors, in particular highly specific inhibitors for epigenetic reader domains.
The first potent inhibitor developed by Prof Knapp and colleagues validated epigenetic reader domains as target for cancer therapy which led to a diverse set of highly selective inhibitors targeting these proteins. Prof Knapp’s work has provided new insights into chromatin biology and paved the way for more than 25 clinical trials in this new area of drug discovery.
Prof Stefan Knapp studied Chemistry at the University of Marburg (Germany) and at the University of Illinois (USA). He did his PhD in protein crystallography at the Karolinska Institute in Stockholm (Sweden) (1996). In 1999, he joined the Pharmacia Corporation, where he worked for five years as a principal research scientist in structural biology and biophysics. In 2004, he set up a research group at the Structural Genomics Consortium at Oxford University (SGC). From 2008 to 2015 he was a Professor of Structural Biology at the Nuffield Department of Clinical Medicine (NDM) at Oxford University (UK) and between 2012 and 2015 he was the Director for Chemical Biology at the Target Discovery Institute (TDI). He joined Frankfurt University (Germany) in 2015 as a Professor of Pharmaceutical Chemistry and the Buchmann Institute of Molecular Life Sciences. He has been the CSO of the newly founded SGC node at the Goethe-University Frankfurt since 2017.
About EMBO // EMBO is an organization of more than 1800 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work.
Further Information: Prof. Stefan Knapp, Institute of Pharmaceutical Chemistry and Buchmann Institute of Molecular Life Sciences, Faculty of Biochemistry, Chemistry and Pharmacy, Tel.: +49 (0) 69 798-29871, Knapp@pharmchem.uni-frankfurt.de
Climate researcher from the program “Make Our Planet Great Again“ coming from the US to the Goethe University
FRANKFURT. Following the Paris Climate Agreement, Germany and France created the program “Make Our Planet Great Again,“ to promote climate change research. One of 13 researchers selected by an expert jury of the German Academic Exchange Service (DAAD) is coming from the USA to the Goethe University in a few months.
The climate change researcher Dr. Anna Possner is leaving the renowned Carnegie Institution for Science in Stanford and will join the Department for Atmospheric and Environmental Sciences at the Goethe University. Thanks to a one million euro grant, she will start her own research group in Frankfurt. This group will cooperate with the Frankfurt Institute for Advanced Studies (FIAS), where it will also be located.
Anna Possner’s research focuses on layered clouds in the lowest kilometres of the atmosphere, which act as a semi-transparent parasol for Earth’s surface. They reflect a significant portion of incoming sunlight, but only marginally affect Earth’s heat emission. They thus have a cooling effect on Earth’s surface. Any sheet of low-level cloud may span hundreds of kilometres and all together they span around one fifth of Earth’s oceans. Changes in their areal extent or reflective properties can result in significant changes to Earth’s surface temperature.
In some regions of the globe, the mid-latitudes and the Arctic, these clouds consist not only of water drops, but may contain a mixture of ice particles and water drops. The proportion of water drops to ice crystals affects the clouds’ reflective properties. “While we have hypotheses about how the radiative properties may be affected within a single cloud,” Anna Possner explains, “we are limited in our understanding of how the presence of ice crystals impacts the areal coverage and reflective properties on the scale of an entire cloud field.” She will use satellite retrievals and sophisticated numerical models to help answer this question.
Since completing her doctoral dissertation at the ETH Zurich, Anna Possner, who was born in Jena, has studied the impact of particles on the reflective properties of clouds. During this time she focused in particular on low-lying clouds over the oceans, where she quantified and evaluated the impact of ship emissions on clouds. During her postdoc years at the ETH Zurich and the Carnegie Institution for Science in Stanford, she extended her analyses to include mixed-phase clouds.
The German-French program “Make Our Planet Great Again“ seeks to support the creation of solid facts as a basis for political decisions in the fields “climate change”, “earth system research” and “energy transformation”. Of the 13 scientists selected for Germany, seven are in the US, two were most recently working in Great Britain and one each is in Switzerland, Canada, South Korea and Australia. They were selected during a two-stage process out of approximately 300 applications.
Further Information: Prof. Joachim Curtius, Department for Atmospheric and Environmental Sciences, Faculty for Geosciences / Geography, Riedberg Campus, Tel.: +49 (0) 798-42058, email@example.com.
Empirical study on historical development allows a prognosis
FRANKFURT. Since first being awarded in 1901, most Nobel Prizes for science have gone to the USA, the United Kingdom, Germany and France. An empirical study by Professor Claudius Gros from the Institute for Theoretical Physics at the Goethe University in Frankfurt has now shown that the Nobel Prize productivity in these countries is primarily determined by two factors: a long-term success rate, and periods during which each country has been able to win an especially large number of Nobel Prizes.
For the study, Nobel Prizes for physics, chemistry and medicine were assigned proportionately, since up to three scientists can share the prize. The success rates were calculated on the basis of population figures. For France and Germany, the periods of increased scientific creativity occurred around 1900, whereas for the USA it occurred in the second half of the 20th century.
“The US era is approaching its end,” states Claudius Gros. “Since its zenith in the 1970s, US Nobel Prize productivity has already declined by a factor of 2.4.” According to his calculations, a further decline is foreseeable. “Our model predicts that starting in 2025 the productivity of the USA will be below that of Germany, and from 2028, below that of France as well.”
With a nearly constant, very high success rate per capita, Great Britain occupies a special position with regard to Nobel Prizes. It remains uncertain, however, whether Great Britain will be able to maintain this success, especially in view of the increasing industrialization of research.
“National research advancement can undoubtedly also be successful independent of Nobel Prize productivity,“ Claudius Gros stresses. “Especially because new areas of research such as the computer sciences – a typical US domain – are not included.” It therefore remains open whether the decline in Nobel Prize productivity is cause for concern, or merely an expression of a new orientation toward more promising research fields.
A chart to download can be found at: www.uni-frankfurt.de/71881831
Chart: Claudius Gros, Goethe University
Claudius Gros: An empirical study of the per capita yield of science Nobel Prizes: Is the US era coming to an end?, in: Royal Society Open Science (2018) http://rsos.royalsocietypublishing.org/content/5/5/180167
Claudius Gros: Pushing the complexity barrier: diminishing returns in the sciences, in: Complex Systems 21, 183 (2012). https://arxiv.org/abs/1209.2725
Further information: Prof. Claudius Gros, Department for Theoretical Physics, Faculty of Physics, Riedberg Campus, Tel.:+49(0)69 798-47818, firstname.lastname@example.org.
Scientists at the Goethe University have discovered that single cells in the innermost layer of blood vessels proliferate after injury and in so doing make a significant contribution to the formation of new vessels.
FRANKFURT. How new blood vessels form in mammals, for example during development or after injury, was so far not known exactly. Scientists at the Goethe University have now been able to shed light on this process. They have shown that single cells in the innermost layer of blood vessels proliferate after injury and in so doing make a significant contribution to the formation of new vessels.
Observation in the living organism – and especially in the heart – of how new blood vessels form is not possible in mammals. That is why only endpoints can ever be seen, i.e. that new veins and arteries have formed and of what type of cells they consist. However, little is known to date about the actual process of new vessel formation, although this knowledge could contribute in future to remedying tissue damage, such as occurs in diabetes or following an ischemia-induced heart attack.
That is the reason why Professor Stefanie Dimmeler and her fellow researchers at the Institute of Cardiovascular Regeneration of Goethe University Frankfurt have studied the fate of single cells in the innermost vascular layer, i.e. the endothelial cells, during development and after tissue damage in what are known as Confetti mice. In these models, the researchers can mark specific cell types and distinguish between them with the help of fluorescent proteins. In the models used, only endothelial cells fluoresced in three different colors. Since the cells continue to fluoresce when they divide, single endothelial cells and their “progeny” can be tracked. In so doing, the scientists sought to answer the question of whether cell division in the formation of new blood vessels, as known from zebrafish, takes place more or less randomly or whether specific cells divide again and again to produce new vessels.
Clonal expansion after a heart attack
In damaged heart tissue following a heart attack, the researchers were able to observe that certain cells had divided repeatedly. They also detected this cell division, which is referred to as clonal expansion, in damaged tissue in skeletal muscles caused by ischemia. To do so, they analyzed the fluorescence in endothelial cells in tissue slices taken from the damaged areas. They found the ratio of clonally expanding cells – between 30 and 50 percent - very surprising. “But perhaps we’re even underestimating the ratio of clonal expansion,” presumes Dimmeler. “Because after all we haven’t conducted a three-dimensional analysis but instead identified the fluorescing cells in two-dimensional tissue slices.” In addition, further experiments showed that the vessels formed through clonal expansion are also supplied with blood and thus able to function.
In new-born models, by contrast, Professor Dimmeler and her team did not observe any clonal expansion in the formation of new vessels in the retina. It would therefore seem that the growth of blood vessels during normal development results from the random multiplication and integration of cells. This result coincides with observations in zebrafish, in which what is known as “cell mixing” also plays an important role in the formation of new blood vessels during development.
The researchers were keen to characterize the dividing cells more precisely and to this purpose they analyzed which genes are transcribed in single examples of the clonally expanding endothelial cells. “Surprisingly, we found a large number of gene products that are typical for the transition from an endothelial to a mesenchymal cell,” says Dimmeler. This transition, or EndMT process, is a contributor in many pathogenic processes, such as scarring or arteriosclerosis. In endothelial cells, the gene products typical for EndMT do not, however, mirror a transition but instead presumably just an intermediate stage that enables the cells to detach themselves from the cell assembly in order to multiply.
Clonal expansion as possible therapy for heart attack patients
Dimmeler and her team now want to find out what happens with the clonally expanded cells in the long term, since at present they are only able to track their fate for about two months. “We want to know what has happened to these cells after a year and whether the new blood vessels are just as good as the old ones in the long term,” says Dimmeler.
Is clonal expansion different in older patients? This is another question she finds fascinating. “It might be that clonal expansion is no longer that efficient in older people, which is why a lot of damaged tissue dies off after a heart attack and forms scar tissue which cannot be reactivated through the formation of new blood vessels,” says Dimmeler. “If we manage to characterize the clonally expanding cells more precisely, we will hopefully find ways to re-stimulate this process.”
Clonal Expansion of Endothelial Cells Contributes to Ischemia-Induced Neovascularization. Manavski, Y., Lucas, T., Glaser, S. F., Dorsheimer, L., Gunther, S., Braun, T., Rieger, M. A., Zeiher, A. M., Boon, R. A. & Dimmeler, S. Circulation research 122, 670-677, (2018).
Further information: Professor Stefanie Dimmeler, Institute of Cardiovascular Regeneration, University Hospital Frankfurt, Tel.: +49(0)69-6301-7440; Email: Dimmeler@em.uni-frankfurt.de
Research group simulates effect of these climate protection goals on global freshwater resources
FRANKFURT. What difference does it make to the Earth’s water resources if we can limit global warming to 1.5°C instead of 2°C? A research group led by Goethe University Frankfurt has simulated these scenarios with global hydrological models. An important result: High flows and thus flood hazards will increase significantly over an average of 21 percent of the global land area if the temperature rises by 2°C. On the other hand, if we manage to limit the rise in global warming to 1.5°C only 11 percent of the global land area would be affected.
According to the Paris Agreement on climate change of December 2015, the increase in global average temperature should be kept well below 2°C compared to pre-industrial levels, if possible even below 1.5°C. To find out what the two scenarios mean specifically in terms of reducing risks for the global freshwater system, the Federal Ministry of Education and Research commissioned a study which has now been published and is intended for inclusion in the forthcoming special report by the Intergovernmental Panel on Climate Change (IPCC) on global warming of 1.5°C.
As the research group led by Professor Petra Döll from the Department of Physical Geography at Goethe University Frankfurt reports in the current issue of “Environmental Research Letters”, it used two global hydrological models for the analysis, which were “fed” with a new type of climate simulations, known as HAPPI simulations. These are more suitable than previous types of simulations for quantifying the risks of the two long-term climate goals. By calculating seven indicators, risks for humans, freshwater organisms and vegetation were characterized.
“If we compare four groups of countries with different per-capita incomes, those countries with a low or lower middle income would profit most from a limitation of global warming to 1.5°C in the sense that the increase in flood risk in those countries would remain far lower than at 2°C,” explains Petra Döll, first author of the study. Countries with a high income would profit most of all from the fact that rivers and land would dry out far less in the dry months of the year.
Professor Döll performed the study in cooperation with the Potsdam Institute for Climate Impact Research and Climate Analytics in Berlin. She is an expert on water and has been investigating the potential impacts of climate change on the Earth’s freshwater systems for twenty years.
A picture can be downloaded under: http://www.uni-frankfurt.de/71631166
Caption: Access to clean water is a major challenge facing many people, such as this boy in the semi-arid Northeast Region of Brazil. Photo: Petra Döll.
Publication: Petra Döll, Tim Trautmann, Dieter Gerten, Hannes Müller Schmied, Sebastian Ostberg, Fahad Saaed und Carl-Friedrich Schleussner: Risks for the global freshwater system at 1.5 ◦C and 2 ◦C global warming, in: Enviromental Research Letters 13 (2018) 044038, https://doi.org/10.1088/1748-9326/aab792
Further information: Professor Petra Döll, Department of Physical Geography, Faculty of Geosciences and Geography, Riedberg Campus, Tel.: +49(0)69-798-40219, email@example.com