Press releases

FRANKFURT. Corals and cave carbonates are important archives of past climate. This is because the composition of these carbonate deposits can reveal the temperatures that prevailed at the Earth’s surface at the time they formed. An international team of geoscientists led by Goethe University Frankfurt, Germany, has now developed a new method that makes it possible to identify whether the composition of these deposits was exclusively controlled by temperature, or if the formation process itself exerted an additional control. The new method allows scientists to determine past Earth surface temperatures more reliably and to study the processes involved in calcareous skeleton formation of modern and extinct species. (Nature Communications, DOI 10.1038/s41467-020-17501-0)

Corals precipitate their calcareous skeletons (calcium carbonate) from seawater. Over thousands of years, vast coral reefs form due to the deposition of this calcium carbonate. During precipitation, corals prefer carbonate groups containing specific variants of oxygen (chemical symbol: O). For example, the lower the water temperature, the higher the abundance of a heavy oxygen variant, known as isotope 18O, within the precipitated carbonate. Unfortunately, the 18O abundance of the seawater also influences the abundance of 18O in the calcium carbonate – and the contribution of 18O from seawater cannot be resolved when determining temperatures based on carbonate 18O abundances alone.

A great step forward was the discovery that the isotopic composition of the precipitated carbonate allows temperature determinations independent of the composition of the water if the abundance of a specific, very rare carbonate group is measured. This carbonate group contains two heavy isotopes, a heavy carbon isotope (13C) and a heavy oxygen isotope (18O) which are referred to as “clumped isotopes”. Clumped isotopes are more abundant at lower temperatures.

However, even with this method there was still a problem: The mineralization process itself can affect the incorporation of heavy isotopes in the calcium carbonate (kinetic effects). If unidentified, the bias introduced by such kinetic effects leads to inaccurate temperature determinations. This particularly applies for climatic archives like corals and cave carbonates.

An international research group led by Professor Jens Fiebig at the Department of Geosciences at Goethe University Frankfurt has now found a solution to this problem. They have developed a highly sensitive method by which – in addition to the carbonate group containing 13C and 18O – the abundance of another, even rarer carbonate group can be determined with very high precision. This group also contains two heavy isotopes, namely two heavy oxygen isotopes (18O).

If the theoretical abundances of these two rare carbonate groups are plotted against each other in a graph, the influence of the temperature is represented by a straight line. If, for a given sample, the measured abundances of the two heavy carbonate groups produce a point away from the straight line, this deviation is due to the influence of the mineralization process.

David Bajnai, Fiebig’s former PhD student, applied this method to various climatic archives. Among others, he examined various coral species, cave carbonates and the fossil skeleton of a squid-like cephalopod (belemnite).

Today, Dr. Bajnai is a post-doctoral researcher at the University of Cologne. He explains: “We were able to show that – in addition to temperature – the mechanisms of mineralization also greatly affect the composition of many of the carbonates that we examined. In the case of cave carbonates and corals, the observed deviations from the exclusive temperature control confirm model calculations of the respective mineralization processes conducted by Dr. Weifu Guo, our collaborator at the Woods Hole Oceanographic Institution in the USA. The new method, for the first time, makes it possible to quantitatively assess the influence of the mineralization process itself. This way, the exact temperature of carbonate formation can be determined.”

Professor Jens Fiebig is convinced that the new method holds great potential: “We will further validate our new method and identify climatic archives that are particularly suitable for an accurate and highly precise reconstruction of past Earth surface temperatures. We also intend to use our method to study the effect that anthropogenic ocean acidification has on carbonate mineralization, for instance in corals. The new method might even allow us to estimate the pH values of earlier oceans.” If all this succeeds, the reconstruction of environmental conditions that prevailed throughout Earth’s history could be greatly improved, he adds.

Publication: David Bajnai, Weifu Guo, Christoph Spötl, Tyler B. Coplen, Katharina Methner, Niklas

Löffler, Emilija Krsnik, Eberhard Gischler, Maximilian Hansen, Daniela Henkel, Gregory D. Price, Jacek Raddatz, Denis Scholz, Jens Fiebig: Dual clumped isotope thermometry resolves kinetic biases in carbonate formation temperatures, Nature Communications, DOI 10.1038/s41467-020-17501-0, http://www.nature.com/ncomms

Further information:
Professor Jens Fiebig
Department of Geosciences
Goethe University Frankfurt
Tel.: +49 (0) 69 798 40182
Jens.Fiebig@em.uni-frankfurt.de

Dr. David Bajnai
Institute of Geology and Mineralogy
University of Cologne
Tel.: +49 (0)221 470 89829

David.Bajnai@uni-koeln.de
Dr. Weifu Guo
Department of Geology and Geophysics
Woods Hole Oceanographic Institution
Woods Hole, MA
USA
Tel.: +1 508 289 3380
wfguo@whoi.edu

FRANKFURT. Researchers from Goethe University have found what is perhaps the oldest enzyme in cellular respiration. They have now been able to isolate an extremely fragile protein complex called “Rnf" from the heat-loving bacterium Thermotoga maritima. In fact, the genes that encode for the enzyme were already discovered around 10 years ago. However, the researchers from Frankfurt have now succeeded for the first time in isolating the enzyme and thus in proving that it really is formed by bacteria and used for cellular energy production. (Communications Biology, DOI 10.1038/s42003-020-01158 -y)

In the first billion years, there was no oxygen on Earth. Life developed in an anoxic environment. Early bacteria probably obtained their energy by breaking down various substances by means of fermentation. However, there also seems to have been a kind of “oxygen-free respiration". This was suggested by studies on primordial microbes that are still found in anoxic habitats today.

“We already saw ten years ago that there are genes in these microbes that perhaps encode for a primordial respiration enzyme. Since then, we – as well as other groups worldwide – have attempted to prove the existence of this respiratory enzyme and to isolate it. For a long time unsuccessfully because the complex was too fragile and fell apart at each attempt to isolate it from the membrane. We found the fragments, but were unable to piece them together again," explains Professor Volker Müller from the Department of Molecular Microbiology and Bioenergetics at Goethe University.  

Through hard work and perseverance, his doctoral researchers Martin Kuhns and Dragan Trifunovic then achieved a breakthrough in two successive doctoral theses. “In our desperation, we at some point took a heat-loving bacterium, Thermotoga maritima, which grows at temperatures between 60 and 90°C," explains Dragan Trifunovic, who will shortly complete his doctorate. “Thermotoga also contains Rnf genes, and we hoped that the Rnf enzyme in this bacterium would be a bit more stable. Over the years, we then managed to develop a method for isolating the entire Rnf enzyme from the membrane of these bacteria."

As the researchers report in their current paper, the enzyme complex functions a bit like a pumped-storage power plant that pumps water into a lake higher up and produces electricity via a turbine from the water flowing back down again.

Only in the bacterial cell the Rnf enzyme (biochemical name = ferredoxin:NAD-oxidoreductase) transports sodium ions out of the cell's interior via the cell membrane to the outside and in so doing produces an electric field. This electric field is used to drive a cellular “turbine" (ATP synthase): It allows the sodium ions to flow back along the electric field into the cell's interior and in so doing it obtains energy in the form of the cellular energy currency ATP.  

The biochemical proof and the bioenergetic characterization of this primordial Rnf enzyme explains how first forms of life produced the central energy currency ATP. The Rnf enzyme evidently functions so well that it is still contained in many bacteria and some archaea today, in some pathogenic bacteria as well where the role of the Rnf enzyme is still entirely unclear.
“Our studies thus radiate far beyond the organism Thermotoga maritima under investigation and are extremely important for bacterial physiology in general," explains Müller, adding that it is important now to understand exactly how the Rnf enzyme works and what role the individual parts play. “I'm happy to say that we're well on the way here, since we're meanwhile able to produce the Rnf enzyme ourselves using genetic engineering methods," he continues.


Publication: Kuhns, M, Trifunovic, D., Huber, H., Müller, V. (2020). The Rnf complex is a Na+ coupled respiratory enzyme in a fermenting bacterium, Thermotoga maritima. Communications Biology, DOI 10.1038/s42003-020-01158-y https://www.nature.com/commsbio/

A Photo is available here: http://www.uni-frankfurt.de/90861461

Caption: Ph.D. student Dragan Trifunovic with a big bottle and a small test tube containing cultured Thermotoga maritima bacteria (Photo: Uwe Dettmar for Goethe University Frankfurt)


Further Information:
Prof. Volker Müller
Molecular Microbiology and Bioenergetics
Goethe-University Frankfurt
Tel.: (069) 798-29507;
vmueller@bio.uni-frankfurt.de

FRANKFURT. The Institute of Medical Virology at Goethe-University, Frankfurt am Main, Germany, and the University of Kent’s School of Biosciences (UK) have identified that a glycoprotein known as transferrin may critically contribute to severe forms of COVID-19.

SARS-CoV-2 is the coronavirus that causes COVID-19. It is currently not known why some individuals develop only mild or no symptoms when infected, whilst others experience severe, life-threatening forms of the disease. However, it is known that the risk of COVID-19 becoming severe increases with age and is higher in males than in females. Many severe COVID-19 cases are characterised by increased blood clotting and thrombosis formation.

The team combined existing data on gene expression in humans with cell culture research of SARS-CoV-2-infected cells to search for molecules involved in blood coagulation that differ between females and males, change with age, and are regulated in response to SARS-CoV-2 infection.

Out of more than 200 candidate factors, researchers identified a glycoprotein called transferrin to be a procoagulant (a cause of blood clotting) that increases with age, is higher in males than in females, and is higher in SARS-CoV-2-infected cells. Hence, transferrin may have potential as a biomarker for the early identification of COVID-19 patients at high risk of severe disease.

Publication: Katie-May McLaughlin, Marco Bechtel, Denisa Bojkova, Christian Münch, Sandra Ciesek, Mark N. Wass, Martin Michaelis, Jindrich Cinatl, Jr.: COVID-19-Related Coagulopathy - Is Transferrin a Missing Link? Diagnostics 2020, 10(8), 539; https://doi.org/10.3390/diagnostics10080539

Further information:
Prof. Dr. rer. nat. Jindrich Cinatl
Institute for Medical Virology
University Hospital Frankfurt
Tel.: +49 69 6301-6409
E-mail: cinatl@em.uni-frankfurt.de

FRANKFURT. When the SARS-CoV-2 virus penetrates human cells, it lets the human host cell produce proteins for it. One of these viral proteins, called PLpro, is essential for the replication and rapid spread of the virus. An international team of researchers led by Goethe University and University Hospital Frankfurt has now discovered that the pharmacological inhibition of this viral enzyme not only blocks virus replication but also strengthens the anti-viral immune response at the same time (Nature, DOI 10.1038/s41586-020-2601-5).

In the case of an infection, the SARS-CoV-2 virus must overcome various defense mechanisms of the human body, including its non-specific or innate immune defense. During this process, infected body cells release messenger substances known as type 1 interferons. These attract natural killer cells, which kill the infected cells.

One of the reasons the SARS-CoV-2 virus is so successful – and thus dangerous – is that it can suppress the non-specific immune response. In addition, it lets the human cell produce the viral protein PLpro (papain-like protease). PLpro has two functions: It plays a role in the maturation and release of new viral particles, and it suppresses the development of type 1 interferons. The German and Dutch researchers have now been able to monitor these processes in cell culture experiments. Moreover, if they blocked PLpro, virus production was inhibited and the innate immune response of the human cells was strengthened at the same time.
 
Professor Ivan Đikić, Director of the Institute of Biochemistry II at University Hospital Frankfurt and last author of the paper, explains: “We used the compound GRL-0617, a non-covalent inhibitor of PLpro, and examined its mode of action very closely in terms of biochemistry, structure and function. We concluded that inhibiting PLpro is a very promising double-hit therapeutic strategy against COVID-19. The further development of PLpro-inhibiting substance classes for use in clinical trials is now a key challenge for this therapeutic approach."

Another important finding from this work is that the viral protein PLpro of SARS-CoV-2 cleaves off ISG-15 (interferon-stimulated gene 15) from cellular proteins with a higher level of activity than the SARS equivalent, which leads to greater inhibition of type I interferon production. This is concordant with recent clinical observations which show that COVID-19 exhibits a reduced interferon response in comparison to other respiratory viruses such as influenza and SARS.

To understand in detail how inhibiting PLpro stops the virus, researchers in Frankfurt, Munich, Mainz, Freiburg and Leiden have worked closely together and pooled their biochemical, structural, IT and virological expertise.
Donghyuk Shin, postdoctoral researcher and first author of the paper, says: “Personally, I would like to underline the significance of science and research and in particular emphasize the potential generated by a culture of collaboration. When I saw our joint results, I was immensely grateful for being a researcher."

Professor Sandra Ciesek, Director of the Institute of Medical Virology at University Hospital Frankfurt, explains that the papain-like protease is an extremely attractive anti-viral goal for her as a physician because its inhibition would be a “double strike" against SARS-CoV-2. She highlights the excellent collaboration between the two institutes: “Especially when investigating a new clinical picture, everyone profits from interdisciplinary collaboration as well as different experiences and viewpoints."


Publication: Donghyuk Shin, Rukmini Mukherjee, Diana Grewe, Denisa Bojkova, Kheewoong Baek, Anshu Bhattacharya, Laura Schulz, Marek Widera, Ahmad Reza Mehdipour, Georg Tascher, Klaus-Peter Knobeloch, Krishnaraj Rajalingam, Huib Ovaa, Brenda Schulman, Jindrich Cinatl, Gerhard Hummer, Sandra Ciesek, Ivan Dikic. Inhibition of papain-like protease PLpro blocks 1 SARS-CoV-2 spread and 2 promotes anti-viral immunity. Nature, DOI 10.1038/s41586-020-2601-5, https://www.nature.com/articles/s41586-020-2601-5

Further information:
Professor Ivan Đikić
Director of the Institute of Biochemistry II of University Hospital Frankfurt
Group Leader at the Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt
Max Planck Fellow at Max Planck Institute of Biophysics, Frankfurt
Tel.: +49 (0)69 6301-5964, email: dikic@biochem2.uni-frankfurt.de, Twitter: @iDikic2

FRANKFURT. The hurricanes in the Caribbean became more frequent and their force varied noticeably around the same time that classical Mayan culture in Central America suffered its final demise: We can gain these and other insights by looking at the climate archive created under the leadership of geoscientists from Goethe University and now presented in an article in “Nature" journal's “Scientific Reports" on 16 July.

Tropical cyclones in the Atlantic (hurricanes) are a substantial threat for the lives and property of the local population in the Caribbean and neighboring regions, such as the south-east of the USA. The storms' increasing force, described in Chapter 15 of the report by the Intergovernmental Panel on Climate Change (IPCC Report), raises the probability of ecological and social catastrophes, as the occurrence of such cyclones over the past 20 years, which caused devastating damage, has shown. The climate models used to date, which could help to estimate the danger better, are, however, based on data that are lacking in spatial and temporal depth. Instrumental climate data, such as regular measurement of sea surface temperatures and reliable chronicling of hurricanes, date back only to the 19th century, at most.

In the framework of a research project (Gi 222/31) funded by the German Research Foundation, the Biosedimentology Working Group at the Department of Geosciences of the Faculty of Geosciences and Geography (Professor Eberhard Gischler) of Goethe University has now been able to build up and analyze a sedimentary “storm archive" that covers almost the entire Common Era (2,000 years) with annual resolution. The archive comprises fine-grained annual layers of sediments from the 125-meter-deep bottom of the Blue Hole, a flooded karst sinkhole on the Lighthouse Reef Atoll off the coast of Belize (Central America). There, 2.5 mm of lime mud, composed of shell debris from organisms in the reef lagoon along with changing amounts of organic matter, collect year after year. Coarser layers up to several centimeters thick that constitute tempestites (storm sediments) are intercalated in these fine-grained sediments. They mostly consist of shell debris from reef organisms living on the edge of the atoll. The almost 9-metre-long drill core from the bottom of the Blue Hole, which was recovered with the help of an electrical vibracorer, spans the last 1,885 years with a total of 157 storm layers.

In the framework of extensive studies conducted by doctoral researcher Dominik Schmitt and collaboration between the Biosedimentology Working Group and colleagues at the University of Bern (Switzerland), it has become apparent that both short-term and long-term climate phenomena, such as the El Niño Southern Oscillation (ENSO), the North Atlantic Oscillation (NAO) and the Atlantic Multidecadal Oscillation (AMO), have influenced storm activity over the last 2,000 years and are mirrored in the new climate archive. The beginning of the Medieval Warm Period (approx. AD 900-1100) constitutes an important transition period when the activity of tropical cyclones changed substantially, presumably in conjunction with the shift of the Intertropical Convergence Zone (the low-pressure zone where northern and southern trade winds converge) towards the south: From AD 100-900, storm activity in the region tended to be more stable and weaker, while since AD 900 up until today it has been more variable and more vigorous. Interestingly, this change in the increase of cyclone frequency goes hand in hand with the occurrence of a few, very thick, coarse-grained storm layers and coincides with the final demise of the classical Mayan culture in Central America. It is possible that the increased impact of hurricanes on the Central American mainland, combined with extensive flooding of cultivated land in the Mayan lowlands and rainfall-induced erosion in the backlands of the Mayan Mountains of Belize – apart from the recurring periods of drought already known – was another environmental factor that influenced the end of the Maya's high culture.


Publication: https://www.nature.com

Images are available for download under the following link: www.uni-frankfurt.de/90131465

Captions:
Picture 1: Aerial photograph of the Blue Hole, a flooded karst sinkhole on Lighthouse Reef, Belize, where the research team from Frankfurt was able to tap into 2,000-year-old sediment layers. (Photo: Gischler)

Picture 2: This drill core section from the Blue Hole shows the annual layering (green-beige) and storm events (light-colored). (Photo: Schmitt)

Further information: Professor Eberhard Gischler, Department of Geosciences, Riedberg Campus, Tel.: +49(0)69-798 40183, email: gischler@em.uni-frankfurt.de