News

Research / 10.07.2024
The Imaging Innovation Center hits a milestone

Photo: Karsten Hönig
Photo: Karsten Hönig

The Max Delbrück Center, Berlin, celebrates its new, innovative research building with a “topping-out ceremony.” The Imaging Innovation Center, designed by the architectural firm heinlewischer, will host researchers specializing in imaging and analysis alongside data experts under one roof starting in 2026.

A state-of-the-art facility for leading researchers in imaging and AI is almost complete: After nearly a year and a half of construction, the architects, builders and scientists is celebrating the new Imaging Innovation Center (IIC) of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association with a “topping out ceremony” on July 11, 2024, on the Campus Buch in Berlin. In the new building, research teams and technology experts from the Max Delbrück Center, including the platforms for Advanced Light Microscopy and Electron Microscopy, as well as new working groups, will cooperate closely to develop imaging technologies starting in 2026. The new IIC will integrate imaging with data analyses and include AI-supported methods. Physicists, biophysicists, life scientists, and bioinformaticians will work closely together. Additionally, companies will have the opportunity to test and make available the latest developments in a "Demonstrator Space for Microscopy."

Imaging as a driving force in biomedicine

"Imaging techniques significantly advance biomedical research and have led to revolutionary discoveries. Any innovation in microscopy that allows us to observe biological phenomena between molecules in cells, organs, and the organism with higher temporal and spatial resolution can dramatically change our understanding of diseases," said Professor Holger Gerhardt, Deputy Scientific Director of the Max Delbrück Center, at the topping-out ceremony. He further added: "Investing in the use and development of imaging techniques and image data analysis in our new IIC is an important strategic positioning. It is essential to fulfill our mission: Discovery for Tomorrow's Medicine."

Heike Graßmann, Administrative Director of the Max Delbrück Center, expressed gratitude to the federal and state governments as well as all the companies and craftsmen involved in the construction: "If you want to enable world-leading research in Berlin in the coming decades, you have to invest wisely today. Thanks to the strategically forward-looking decision by the federal and state governments, we are able to invest nearly 32 million euros in the construction of this new life sciences research building on our campus. I am particularly pleased that we have managed to advance the construction so significantly in just one and a half years by working together diligently."

Highly sensitive microscopy on almost 3000 square meters

The three-and-a-half-story building with a total usable area of 2.675 square meters was planned by the architects at heinlewischer, which has already realized several buildings on the campus. The construction costs of the publically funded building, originally to be named Optical Imaging Center, amount to €31,873 million. The building is located directly next to the Isolde-Diedrich House for Cryo-Electron Microscopy and integrates ideally into the ensemble of research buildings on the campus. Like the Cryo-EM, the IIC rests on a massive base plate that compensates for shifts in the building’s structure. This low-vibration construction, ensures that the highly sensitive light and electron microscopes are not affected by any movement. A highly precise air conditioning system will ensure stable temperature and constant humidity in the laboratories. The building will be built to the highest energy conservation standards, i.e., prepared for the transition to future energy sources and is equipped with photovoltaics and geothermal collectors; it is expected to receive the silver certificate of the sustainable building rating system BNB.

The architect Dr. Alexander Gyalokay from heinlewischer said: "It is always a challenge to meet the specific requirements of science on the one hand and the demands for flexibility and cost-effectiveness on the other. Optical imaging requires vibration-resistant buildings with temperature-stable rooms, which we will construct here in a rare concentration. We are proud to be involved in such a project."

Further Information

 

Research / 08.07.2024
Giant with a Ceramic Heart

Proudly presenting the new NMR spectrometer at the institute. From left to right: Dr. Peter Schmieder, Prof. Dr. Han Sun, Prof. Dr. Adam Lange, Dr. Sigrid Milles, Prof. Dr. Hartmut Oschkinat. (Foto: Silke Oßwald)
Proudly presenting the new NMR spectrometer at the institute. From left to right: Dr. Peter Schmieder, Prof. Dr. Han Sun, Prof. Dr. Adam Lange, Dr. Sigrid Milles, Prof. Dr. Hartmut Oschkinat. (Foto: Silke Oßwald)

A new NMR spectrometer has been in operation at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) since the end of May. What makes it special is that it is based on a new type of ceramic high-temperature superconductor. Peter Schmieder, head of the NMR technology platform at the FMP, explains the technology behind it and the capabilities of the new device.

The first NMR spectrometer was to be installed in the basement, says Peter Schmieder. However, magnets of this magnitude have a very strong magnetic field, and it would have been impractical to clear the ground floor to prevent anyone from working in the field's vicinity. "So, we constructed a separate building for the spectrometer. Later, other devices found a place there, and soon a second building was added," reports the head of the NMR technology platform.

Now, there is no more space in the second building either, and a third one had to be built for the new NMR spectrometer. The device is the eleventh of its kind since researchers at the FMP began conducting studies using nuclear magnetic resonance (NMR) spectroscopy in 1995. Peter Schmieder has been involved from the beginning. He has supervised the construction of each of the devices, all of which are still in operation.

The new device is special because it employs a technology recognized with the Nobel Prize in Physics in 1987: the high-temperature superconductor. "High-temperature means the material develops superconducting properties at a temperature above minus 200 degrees Celsius," explains Peter Schmieder. In this state, the inside of the magnet is free from electrical resistance and provides a stable field after charging without further power supply for many years (persistent magnet). The oldest magnet at the FMP, still with conventional superconductors, has maintained its field for a quarter of a century. This allows for highly precise analyses of increasingly complex biological systems, such as protein structures. "The quality of the measurement, meaning its sensitivity and the resolution in the spectra, depends on the field strength of the magnet – the stronger, the better," says Peter Schmieder.

The magnet in the new device achieves the currently highest possible stable magnetic field of 28 Tesla, which corresponds to a resonance frequency of 1.2 gigahertz (GHz), a 20 percent higher resonance frequency than what could be achieved with conventional superconductors. This is due to the material used: the innermost part of the coil was made with ceramic superconductors, a tricky task because the material is more brittle than metal. The manufacturer worked on this development for over a decade. However, the operating temperature of the new superconductors remains at -271 °C to ensure the material can support the strong magnetic field. The new NMR device on the Buch campus is one of only ten that have been put into operation worldwide so far.

The 28-Tesla field is a million times stronger than Earth's magnetic field. Since the magnets in the NMR devices are shielded and the generated magnetic fields are static and not fluctuating, they pose no problems for healthy people without pacemakers. However, Peter Schmieder and his team leave mobile phones and watches at the door before entering one of the rooms with the NMR spectrometers.

The setup of the new NMR device is now complete. The 8-ton magnet was moved into the building on an air cushion and then positioned vertically. After the setup was completed, it had to be cooled down. "That alone took three weeks. You do it very slowly to avoid mechanical stresses in the coil," reports Peter Schmieder. When the coil reaches a temperature of two Kelvin (-271.15 degrees Celsius or two degrees Celsius above absolute zero), the magnet is charged. This is the tricky part: if something goes wrong, the coil loses its superconductivity, the cooling medium helium warms up and evaporates into the atmosphere, and the entire – expensive and lengthy – process has to be restarted. "But everything went according to plan, the magnet is on field, meaning it has reached its field of 28 Tesla," Peter Schmieder is pleased to report. Afterwards, the hardware was tested to check if the device's specifications regarding electronics and measuring equipment were met.

Since the end of May, the test operation with the first scientific measurements has been running.
"The primary challenge in protein NMR spectroscopy lies in the numerous signals that exhibit only minor differences from one another. This is why achieving high resolution is crucial," says Peter Schmieder. Additionally, this technology is particularly suitable for determining the mobility of proteins. The experimental setup for measurements in solutions or in solids is different, which is why the old NMR devices at the FMP are used for one measurement type each – currently five for solid-state measurements and five for solution measurements. However, the new device is designed to be used for both measurement types. This allows for a wide variety of investigations to be carried out with the new state-of-the-art magnet. The main users of the new device will be the NMR groups working at the FMP. Adam Lange's group uses solid-state NMR to investigate the structure and dynamics of pharmacologically relevant membrane proteins, while in Sigrid Milles' group solution NMR is used to characterize intrinsically disordered proteins (IDPs). Han Sun's group utilizes anisotropic NMR to determine the structure and stereochemistry of small molecules and peptides, while Hartmut Oschkinat's group characterizes biofilm proteins using solution and solid-state NMR.

Source: Press Release LEIBNIZ-FORSCHUNGSINSTITUT FÜR MOLEKULARE PHARMAKOLOGIE (FMP)
Giant with a Ceramic Heart

Research / 05.07.2024
Holger Gerhardt new member of the DZHK Board of Directors

Professor Holger Gerhard (Photo: Pablo Castagnola/Max Delbrück Center)
Professor Holger Gerhard (Photo: Pablo Castagnola/Max Delbrück Center)

Professor Holger Gerhardt from the DZHK partner site Berlin was newly elected to the Board of Directors by the General Assembly: He will take office on 1 July 2024.

Holger Gerhardt succeeds Thomas Sommer and represents the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (Max Delbrück Center) on the DZHK Board of Directors. Together with Stefanie Dimmeler (Wolfgang Goethe University Frankfurt), chairwoman, and Steffen Massberg (Klinikum der Universität München) as member of the board, Holger Gerhardt will remain on the three-member board until the end of 2026. The statutes of the Deutschen Zentrum für Herz-Kreislauf-Forschung (DZHK) stipulate that the Max Delbrück Center and a university or university hospital must be represented on the board. The Max Delbrück Centre is a founding member of the DZHK.

Holger Gerhardt has held a DZHK professorship for Experimental Cardiovascular Research at the Charité in Berlin since 2014 and heads the "Integrative Vascular Biology" working group at the Max Delbrück Centre in Berlin-Buch. He is also Vice-Chairman of the Max Delbrück Center. At the DZHK, the 55-year-old was most recently the spokesperson for the Berlin partner site.

"The DZHK is a globally unique interdisciplinary research network with the task of jointly tackling the growing challenges in the diagnosis, treatment and prevention of cardiovascular diseases. In addition to my research, it is a great pleasure to support the strategic development of the DZHK as a member of the Executive Board.

The biologist investigates how blood vessels form during the development of organisms and looks for ways to stop pathological vessel growth. The aim of his research is to gain a better understanding of blood vessel formation and its dysfunction in diseases, particularly cardiovascular diseases and tumours.

The DZHK board is looking forward to working with Holger Gerhardt and would like to thank Thomas Sommer for his excellent and longstanding cooperation. Sommer, an expert in cellular biochemistry, served as Acting Scientific Director of the Max Delbrück Center from 2014 to 2022, with a three-year break.

Further information

Research / 04.07.2024
New center of excellence for single cell omics

Photo: Max Delbrück Center
Photo: Max Delbrück Center

On July 8, the Max Delbrück Center and Bruker will kick off a strategic partnership to build a first-of-its-kind innovation hub for systems medicine. The new center will focus on the development and application of mass spectrometry based single-cell and multi-omics technologies.

The Max Delbrück Center and Bruker have launched a strategic collaboration that aims to capitalize on the expertise of both partners to accelerate innovations in systems medicine. The partnership will allow Max Delbrück Center scientists and Bruker to work side-by-side on co-creating tools and solutions for precision medicine.

The new “MDC-Bruker Center of Excellence for Single Cell Omics” will be located at the Berlin Institute for Medical Systems Biology of the Max Delbrück Center (MDC-BIMSB) in Berlin-Mitte. The “industry-on-campus” approach will provide scientists at the Max Delbrück Center easy access to the latest mass spectrometry technologies, as well as Bruker’s expertise in single-cell and spatial proteomics. At the same time, Bruker will gain valuable opportunities for clinical applications based on close collaborations with the Max Delbrück Center and its research partners, such as the Charité – Universitätsmedizin Berlin, including within the Einstein Center for Early Disease Interception.

The opening event on July 8 will include a symposium featuring two world-renowned keynote speakers: Professor Matthias Mann, Director of the Max Planck Institute of Biochemistry and a pioneer in mass spectrometry-based proteomics, and Professor Amos Tanay from the Weizmann Institute of Science, who is trailblazing the combination of single-cell work and analysis of massive electronic health records.

Complementary technologies

The Max Delbrück Center has developed innovative single-cell sequencing and spatial technologies that enable scientists to map cells within tissues in 2D and 3D. Additionally, it has established single-cell and spatial proteomics platforms broadly applicable to patient archival samples in various disease contexts. However, understanding health and disease requires the ability to analyze biological information at the genomic, transcriptomic, proteomic and metabolomic level. But so far, most existing methods focus on a single modality.

The proteomic technologies were developed based on Bruker’s timsTOF Ultra system – a highly sensitive mass spectrometer capable of profiling proteins from single cells from cell culture and archived tissue. While this technology provides unprecedented insight into cell-to-cell proteome heterogeneity, it doesn’t provide transcriptomic or metabolomic information, nor does it reveal the dynamics of cellular processes.

Scientific and economic connectivity

Now, the Max Delbrück Center and Bruker plan to expand their cooperation. Their first joint R&D project will create a broadly applicable platform to simultaneously profile proteins and metabolites, as well as lipids to understand disease processes at the level of single or a few cells. Ultimately, the aim is to develop a multi-omics workflow that could be applied in diverse clinical settings. The co-creation project totaling €1.2 million is supported by the Helmholtz Association in the framework of its Transfer campaign. Bruker is co-financing 20 %.

Collaboration between the two partners could lead to a long-term partnership and new joint R&D projects that include external partners to explore new applications of the co-developed single-cell multi-omics platform.

“Projects like this one – and the Center of Excellence as a whole – align perfectly with our strategic goal to adapt emerging technologies for medical innovation,” says Professor Maike Sander, Scientific Director of the Max Delbrück Center. “Our ‘industry-on-campus’ model with Bruker aims to sustainably develop an innovation ecosystem that attracts international talent. Academic and industry partners are already interested in collaborating.”

Dr. Severin Fischer, State Secretary in the Berlin Senate Department for Economics, Energy and Public Enterprises, says: “When science and industry work together, the whole of Berlin wins. We specifically support this and want to develop our city into the number one innovation location in Europe. The pioneering cooperation between the Max Delbrück Center and Bruker is a further step in this direction and shows how we can leverage our great potential for medical progress and economic strength.”

A vibrant environment for biomedical research

“We are very excited to be working with the world-class researchers in proteomics, metabolomics as well as genomics and transcriptomics at the Max Delbrück Center to realize our joint vision of using a multi-omics approach to understanding biology and disease at the single-cell level,” says Dr. Rohan Thakur, President of the Life Science Mass Spectrometry business at Bruker Switzerland AG. “We are also pleased to be making this investment to increase our presence in Berlin, where initiatives supported by the Berlin Senate like the Einstein Center for Early Disease Interception are creating a vibrant and collaborative environment for biomedical research.”

“This unique partnership with Bruker allows us to jointly develop solutions for cell-based interceptive medicine,“ says Professor Nikolaus Rajewsky, Scientific Director of the MDC-BIMSB and co-spokesperson of the Einstein Center. “Our society is aging and chronic and severe diseases such as cancer, neurodegeneration and cardio-vascular diseases are on the rise. To tackle these grand medical challenges, strong interdisciplinary teams of scientists from academia and industry are essential.”

“Through innovations in ultrasensitive mass spectrometry, the proteomics research field has made a significant leap forward in recent years to measure single-cell proteomes at unprecedented biological resolution,” says Dr. Fabian Coscia, head of the Spatial Proteomics Group at the Max Delbrück Center and member of the MDC-Bruker core team. “This is an excellent foundation for our planned activities to further develop this technology for multi-omics approaches and to gain deeper insights into health and disease states.”

Further information

https://www.mdc-berlin.de/news/press/new-center-excellence-single-cell-omics

Research / 03.07.2024
Award for excellent communication on animal research

Through various initiatives, the Max Delbrück Center contributes to an objective debate on animal testing. For the second time, the “Understanding Animal Research” initiative has awarded the center the seal of approval for exemplary communication in experimental animal research.

New immunotherapies against cancer, experiments that can pave the way for new pain medications, hearts that do not scar after a heart attack but renew muscle cells – it would be easy to skip a crucial aspect of scientific successes: animal research. The Max Delbrück Center consciously takes a different path. It communicates openly and transparently when new knowledge is based on experiments involving animals, explaining why these experiments are necessary, what the 3R principles (Replace, Reduce, Refine) entail, and what limitations current alternative methods have.

For this proactive approach, the German initiative “Understanding Animal Research” has awarded the Max Delbrück Center the quality seal of “Quality approval for exemplary communication of experimental animal research” for the second time. For more than ten years, “the center has consistently set standards in educating about animal research, with a clear focus on active dialogue with the public,” the judges stated.

Facilitating direct exchange

In addition to the comprehensive information available on the website, the initiative praises the Max Delbrück Center's events that facilitate direct exchange and encourage scientists to speak openly about animal research: “By actively interacting with the public and supporting educational events, the center contributes to building a productive dialogue on animal research.”

The seal was awarded to five institutions nationwide during the initiative's anniversary event on July 1, 2024. “Understanding Animal Research” was founded by the Alliance of Science Organizations and the German Research Foundation (DFG). The Max Delbrück Center is one of the 53 initial signatories of the Transparency Agreement Initiative, launched in 2021.

Further Information

Innovation / 03.07.2024
Pentixapharm Acquires Target Discovery Business of Glycotope

Würzburg and Berlin, Germany, 3 July 2024 – Pentixapharm AG, a clinical-stage biotech company discovering and developing novel targeted radiopharmaceuticals against a range of malignancies, has announced the execution of an agreement, effective July 1st, to acquire the target discovery business of Berlin-based Glycotope GmbH.

The deal encompasses a portfolio of preclinical antibodies against multiple oncology targets that can be developed into radiopharmaceuticals. It also includes Glycotope’s laboratories, cell banks, tumor target data base, and the equipment needed to exploit the discovery platform, along with a range of patents, licenses, and other tangible assets. In total, Pentixapharm will be able to add an integrated team of 40 seasoned executives, R&D specialists, and administrators to its staff.

“The acquisition will broaden Pentixapharm’s Intellectual Property portfolio beyond the one built around the CXCR4 receptor. This will immediately double the development pipeline and significantly expand the associated business and clinical development opportunities,” explained Hakim Bouterfa, CEO of Pentixapharm AG. “Glycotope’s pipeline comprises several candidates that can be used immediately for proof-of-concept studies as next generation radiopharmaceuticals. We look forward to maximizing the synergy of Pentixapharm’s know-how and Glycotope’s target discovery for the benefit of patients in both diagnostics and therapeutic applications.”

“The transaction provides Pentixapharm not just with a chance to build a clinical pipeline beyond the company’s current CXCR4-ligand based programs, but also substantially strengthens its administrative and managerial capacities,” noted Andreas Eckert, Chairman of the Supervisory Board of both Pentixapharm and mother company Eckert & Ziegler SE (EZAG). “It adds a critical number of talents to the planned secession of Pentixapharm to Frankfurt Stock Exchange, thereby facilitating a seamless separation from EZAG. The offices and laboratories included in the deal are large enough to allow a consolidation of all Berlin-based activities into one loaction."

The transaction will also affect the composition of the Pentixapharm Management Board once the company becomes listed on the Frankfurt Stock Exchange. Hakim Bouterfa, current CEO of Pentixapharm, is designated to move to the Company’s Supervisory Board. He will be succeeded by Dirk Pleimes, currently Pentixapharm’s Chief Medical Officer. Patrik Kehler, former Chief Scientific Officer (CSO) of Glycotope, will assume the CSO position at Pentixapharm, while Glycotope’s former CEO, Henner Kollenberg, will take over the responsibility for administrative and business development issues as Chief Business Officer.

Patrik Kehler, newly appointed Chief Scientific Officer of Pentixapharm, explained: “The target discovery unit’s development activities focus on tumor-associated carbohydrate structures, so-called GlycoTargets. Their major advantage ist the reduced normal tissue binding compared to conventional antibodies. Based on their superior tumor-specificity, they are suitable for development in an array of different modes of action. In the radiopharmaceuticals field, they have the potential to close the treatment gap that exists for the majority of solid tumors.”

About the Glycotope Target Discovery Unit

The target discovery unit utilizes a proprietary technology platform to develop uniquely tumor-specific monoclonal antibodies or fragments thereof. They target specific tumor-associated carbohydrate structures or protein/carbohydrate combined glycoepitopes (GlycoTargets). The unit has to date discovered in excess of 200 GlycoTargets (www.glycotope.com). Many of these have been outlicensed to major pharmaceutical companies around the world, where they are currently in pre-clinical and clinical development.

About Pentixapharm AG

Pentixapharm is a radiopharmaceutical development company founded in 2019 with its headquarters in Würzburg, Germany. It is currently wholly owned by the Eckert & Ziegler Group but bound to be spun-off to the Frankfort Stock Exchange soon. Pentixapharm is committed to developing CXCR4 ligand-based first-in-class radiopharmaceutical approaches with a clear commercial pathway for diagnostic and therapeutic programs in a number of hematological and solid cancers, as well as cardiovascular, endocrine and inflammatory diseases.

Pentixapharm’s clinical pipeline encompasses PENTIXATHER, am Yttrium-90 based therapeutic against CNS lymphoma, and PENTIXAFOR, a Gallium-68 based companion diagnostic. Clinical studies for both compounds have already commenced in Europe, with a dose-finding study for PENTIXATHER and a Phase III registration study for PENTIXAFOR. Additionally, PENTIXAFOR is being developed as a diagnostic tool for primary aldosteronism (PA), a significant cause of hypertension. Pentixapharm is currently preparing a US centric Phase III registration study in PA that will start in 2025.

Innovation / 01.07.2024
Pentixapharm Announces Expansion of Supervisory Board with the Appointment of Distinguished Endocrinologist Marcus Quinkler

Pentixapharm AG, a clinical-stage biotech company discovering and developing novel targeted radiopharmaceuticals against a broad range of malignancies, announced today that the General Shareholder Meeting of Pentixapharm resolved the appointment of the distinguished endocrinologist Prof. Dr. med. Marcus Quinkler to the Company's Supervisory Board. The assignment will become effective with the registration of the split-off of Pentixapharm AG from Eckert & Ziegler SE in the commercial register.

“We welcome Marcus Quinkler as a valuable addition to our Board. He is a recognized expert among others in primary aldosteronism, the focus area of our Phase III lead program PENTIXAFOR (PTF-302). He will also help Pentixapharm to advance its ongoing clinical assessments of the Company’s novel, CXCR4-based radiopharmaceutical therapeutic and diagnostic programs.” explained Dr. Hakim Bouterfa, Founder and Chief Executive Officer of the Pentixapharm Holding AG.

Marcus Quinkler is a specialist of internal medicine and endocrinology, diabetology and andrology. Formerly at the endocrinology department at the Charité-Universitätsmedizin, Campus Mitte, Berlin, currently leading a specialized endocrine practice in Berlin, Dr. Quinkler has significantly contributed to the field, serving as an adjunct professor at Charité.

His academic training includes a medical degree and doctorate from the Free University of Berlin, a research fellowship at the University of Birmingham, U.K., funded by the DFG, and a postdoctoral thesis at the Charité to qualify as a professor. Dr. Quinkler has led significant clinical guideline developments and held editorial roles in prominent journals. His accolades include the Schoeller-Junkmann Prize and the Arthur-Jores Honorary Prize from the German Society for Endocrinology (DGE). From 1996 to 2024, Dr. Quinkler has authored over 270 peer-reviewed publications.

Dr. Marcus Quinkler added: “Pentixapharm’s CXCR4-ligand technologies are being evaluated not only in hematological indications but also for a range of other applications beyond cancer. Notably, their advanced diagnostic program in Primary Aldosteronism holds significant promise as a meaningful alternative to the current gold standard, potentially improving patient outcomes and enhancing cardiovascular health. I am pleased to join the Board at this pivotal moment and support the Company in their future growth.”
Dr. Quinkler will strengthen the Supervisory Board of Pentixapharm AG next to Chairman Dr. Andreas Eckert, Jens Giltsch and Dr. Harald Hasselmann, who also serves as CEO of Eckert & Ziegler SE.

About Pentixapharm AG

Pentixapharm is a radiopharmaceutical development company founded in 2019 with its headquarters in Würzburg, Germany. It is currently wholly owned by the Eckert & Ziegler Group but bound to be spun-off to the Frankfort Stock Exchange soon. Pentixapharm is committed to developing CXCR4 ligand-based first-in-class radiopharmaceutical approaches with a clear commercial pathway for diagnostic and therapeutic programs in a number of hematological and solid cancers, as well as cardiovascular and endocrine diseases.

Pentixapharm’s clinical program encompasses PENTIXATHER, am Yttrium-90 based therapeutic against CNS lymphoma, and PENTIXAFOR, a Gallium-68 based companion diagnostic. Clinical studies for both compounds have already commenced in Europe, with a dose-finding study for PENTIXATHER and a Phase III registration study for PENTIXAFOR.  Additionally, PENTIXAFOR is being developed as a diagnostic tool for primary aldosteronism, a significant cause of hypertension. Pentixapharm aims to initiate an advanced clinical trial in the United States in 2025.

Research / 28.06.2024
Multiple myeloma: Early detection of aggressive tumors

Photo: Pablo Castagnola l Max Delbrück Center
Photo: Pablo Castagnola l Max Delbrück Center

Berlin researchers and their partners describe how aggressive variants of multiple myeloma can be detected early. Their comprehensive study in “Nature Cancer” shows how changes in genetic material affect the protein profile of the tumor cells, and thus the mechanisms involved in the disease.

Multiple myeloma is one of the most common forms of cancer of the immune cells in the bone marrow. Despite advances in treatment and the introduction of new cellular immunotherapies, there is no cure at present. Even when patients respond to treatment at first, the cancer comes back. To be able to intervene faster and on a more targeted basis, a researchers led by Professor Jan Krönke from the Department of Hematology, Oncology and Cancer Immunology at Charité – Universitätsmedizin Berlin, and Dr. Philipp Mertins, head of the Proteomics technology platform of the Max Delbrück Center and the Berlin Institute of Health at Charité (BIH), teamed up with other partners for a comprehensive study of this disease at the molecular level. They now describe how highly aggressive types of tumors can be detected early on in an article published in the journal “Nature Cancer.” They show how changes in genetic material affect the protein profile of the tumor cells, and thus the mechanisms involved in the disease.

In multiple myeloma, the immune cells in the bone marrow, known as plasma cells, mutate and become cancerous. Plasma cells are responsible for producing antibodies. All humans have many different kinds of plasma cells that form large numbers of different antibodies. This allows the body to recognize and fight various pathogens. In multiple myeloma, a single plasma cell mutates into a tumor cell. That cell reproduces unchecked, forming a monoclonal cell population. This means many cells are formed, all of them exactly the same and genetically identical at first. The mutated cells often also produce large volumes of antibodies or fragments of them – but they do not function properly. Over the course of the disease, most patients develop tumors at various locations in the bone marrow, hence the “multiple” in the disease’s name. Immunodeficiency, kidney failure, bone loss, and bone fractures are just some of the consequences of this uncontrolled cell growth.

What path does the tumor take?

No two cases of cancer are alike, and multiple myeloma is no exception. Tumors develop differently in different individuals, including at different rates. This makes it more difficult to predict how the disease will progress and choose the optimum treatment. While the mutated plasma cells do not spread much in some cases, in others they are extremely aggressive, leading to a poor prognosis.

But what causes so much divergence in the course of multiple myeloma? In cooperation with protein analysis experts from the Max Delbrück Center and BIH, the researchers conducted a detailed study of genetic and molecular changes occurring in the tumor cells in a group of more than one hundred patients. The study included data from patients in the German Multiple Myeloma Study Group (DSMM), which is coordinated by the University Hospital of Würzburg. This allowed the researchers to include clinical data on patients who had received standardized treatment over a period of eight years or more following initial diagnosis.

Systems medicine and big data

While changes in the genome and their effects on the proteome are already well described for other types of cancer, this is the first detailed proteo-genomic study of multiple myeloma. “Genetic data alone is insufficient to explain the mechanisms involved in this disease,” Mertins says. “We wanted to know the consequences of genetic changes at the protein level and compare this molecular biology data against the actual course of the disease in patients.” The team was supported in collecting and analyzing the large volumes of data by experts at Charité, BIH, and the German Cancer Consortium (DKTK).

Cutting-edge mass spectrometry methods made it possible to map the protein profile of mutated plasma cells and compare it against that of healthy plasma cells in people without the disease. The researchers found that both genetic changes and changes in signaling pathways lead to uncontrolled activation of cancer cells. Regulatory processes at the protein level had the stronger influence. The researchers identified a protein constellation that suggests the disease will take a particularly aggressive course, regardless of other known risk factors.

Unlocking new therapies

“Our findings will help subcategorize patients more effectively going forward, personalizing their treatment,” Krönke concludes. “We’ve identified key proteins and signaling pathways that can serve as the basis for even more effective, better tolerated treatments for multiple myeloma, for example for immune therapies such as CAR T-cell therapy.” In further steps, the researchers plan to study which of the target structures they have identified are in fact good candidates for new therapeutic approaches.

The study is a crucial resource for research and applied development, says Dr. Evelyn Ramberger, first author of the study: “To make the complex data set manageable, we programmed an interactive, freely available online tool.” This has given cancer researchers easy access to the results, so they can use the information to develop new therapies and tests to help guide treatment. For example, it may be possible to treat patients with an especially aggressive form of multiple myeloma with more intensive therapies right at the outset.

Text: Charité

Source: Joint press release of Charité, BIH at Charité, and the Max Delbrück Center
Multiple myeloma: Early detection of aggressive tumors

Innovation / 27.06.2024
Annual General Meeting of Eckert & Ziegler SE Approves Split-Off of Pentixapharm AG

The Annual General Meeting of Eckert & Ziegler SE (ISIN DE0005659700) today resolved to split-off Pentixapharm AG from Eckert & Ziegler SE and to distribute a dividend of EUR 0.05 per share for the 2023 financial year.

As in the previous year, the Annual General Meeting was held as an in-person event at Eckert & Ziegler SE's headquarters in Berlin. A total of 57.6% of the company's share capital was represented.

The detailed voting results of the Annual General Meeting and the presentation by the Chairman of the Executive Board are published on the Eckert & Ziegler SE website:

About Eckert & Ziegler
Eckert & Ziegler SE with more than 1.000 employees is a leading specialist for isotope-related components in nuclear medicine and radiation therapy. The company offers a broad range of services and products for the radiopharmaceutical industry, from early development work to contract manufacturing and distribution. Eckert & Ziegler shares (ISIN DE0005659700) are listed in the TecDAX index of Deutsche Börse.
 

Source: Press Release Eckert & Ziegler
Annual General Meeting of Eckert & Ziegler SE Approves Split-Off of Pentixapharm AG

Research / 26.06.2024
3D maps of diseased tissues at subcellular precision

2D map of gene expression in the metastatic lymph node Photo: AG N. Rajewsky, Max Delbrück Cente
2D map of gene expression in the metastatic lymph node Photo: AG N. Rajewsky, Max Delbrück Cente

An open-source platform developed by researchers in Nikolaus Rajewsky’s lab at the Max Delbrück Center creates molecular maps from patient tissue samples with subcellular precision, enabling detailed study and potentially enhancing routine clinical pathology. The study was published in “Cell.”

Researchers in the Systems Biology Lab of Professor Nikolaus Rajewsky have developed a spatial transcriptomics platform, called Open-ST, that enables scientists to reconstruct gene expression in cells within a tissue in three dimensions. The platform produces these maps with such high resolution, that researchers are able to see molecular and (sub)cellular structures that are often lost in traditional 2D representations. The paper was published in the journal “Cell.” 

In tissues from the brains of mice, Open-ST was able to reconstruct cell types at subcellular resolution. In tumor tissue and a healthy and metastatic lymph node from a patient with head and neck cancer, the platform captured the diversity of immune, stromal, and tumor cell populations. It also showed that these cell populations were organized around communication hotspots within the primary tumor, but this organization was disrupted in the metastasis.

Such insights can help researchers understand how cancer cells interact with their surroundings and, potentially begin exploring how they evade the immune system. Data can also be used to predict potential drug targets for individual patients. The platform is not restricted to cancer and can be used to study any type of tissue and organism.

“We think these types of technologies will help researchers discover drug targets and new therapies,” says Dr. Nikos Karaiskos, a senior scientist in the Rajewsky lab at the Berlin Institute for Medical Systems Biology of the Max Delbrück Center (MDC-BIMSB) and a corresponding author on the paper.

Unveiling the spatial complexity of tissues

Transcriptomics is the study of gene expression in a cell or a population of cells, but it usually does not include spatial information. Spatial transcriptomics, however, measures RNA expression in space, within a given tissue sample. Open-ST offers a cost-effective, high-resolution, easy-to-use method that captures both tissue morphology and spatial transcriptomics of a tissue section. Serial 2D maps can be aligned, reconstructing the tissue as 3D “virtual tissue blocks.”

“Understanding the spatial relationships among cells in diseased tissues is crucial for deciphering the complex interactions that drive disease progression,” says Rajewsky, who is also Director of MDC-BIMSB. “Open-ST data allow to systematically screen cell-cell interactions to discover mechanisms of health and disease and potential ways to reprogram tissues.”

Open-ST images from cancer tissues also highlighted potential biomarkers at the 3D tumor/lymph node boundary that might serve as new drug targets. “These structures were not visible in 2D analyses and could only be seen in such an unbiased reconstruction of the tissue in 3D,” says Daniel León-Periñán, co-first author on the paper.

“We have achieved a completely different level of precision,” adds Rajewsky. “One can virtually navigate to any location in the 3D reconstruction to identify molecular mechanisms in individual cells, or the boundary between healthy and cancerous cells, for example, which is crucial for understanding how to target disease.”

Cost-effective and accessible technology

One significant advantage of Open-ST is cost. Commercially available spatial transcriptomics tools can be prohibitively expensive. Open-ST, however, uses only standard lab equipment and captures RNA efficiently, reducing costs significantly. Lower costs also mean that researchers can scale up their studies to include large sample sizes, to study patient cohorts, for example.

The researchers have made the entire experimental and computational workflow freely available to enable widespread use. Importantly, the platform is modular, says León-Periñán, so Open-ST can be adapted to suit specific needs. “All the tools are flexible enough that anything can be tweaked or changed.”

“A key goal was to create a method that is not only powerful but also accessible,” says Marie Schott, a technician in the Rajewsky lab and co-first author on the paper. “By reducing the cost and complexity, we hope to democratize the technology and accelerate discovery.”

Text: Gunjan Sinha

 

Source: Press Release Max Delbrück Center
3D maps of diseased tissues at subcellular precision

Innovation / 25.06.2024
Eckert & Ziegler Subsidiary Pentixapharm Receives Encouraging FDA Feedback to Initiate Phase III Trial with PentixaFor as Radiopharmaceutical Diagnostic in Primary Aldosteronism

Pentixapharm AG, a radiopharmaceutical development company wholly owned by Eckert & Ziegler SE, today announced that it has received encouraging feedback from the U.S. Food and Drug Administration (FDA) following a recent Type C meeting with the Agency to directly proceed into a pivotal phase III registration study with its radiopharmaceutical diagnostic Ga68-PentixaFor in Primary Aldosteronism (PA). PA is an adrenal gland disorder also known as Conn’s syndrome and the most frequent cause of secondary hypertension (high blood pressure).

While the FDA minutes from the Type C meeting do not constitute a formal approval of a particular development plan, they indicate that the clinical data compiled by various academic groups independently from Pentixapharm might serve as confirmatory evidence, relieving the Company of the requirement to conduct a second well-controlled clinical investigation. The minutes also confirm that Ga68-PentixaFor addresses an unmet medical need for a serious condition and therefore meets two essential criteria for fast track and breakthrough designation, which Pentixapharm can request with its Investigational New Drug (IND) submission to initiate the phase III trial.


Ga68-PentixaFor is a novel tracer used in the positron emission tomography (PET) imaging of aldosterone-hypersecreting adenomas in patients diagnosed with PA. The estimated prevalence of this disease has increased considerably over the years, exceeding 20% in some populations of resistant hypertension1. The disorder is characterized by either a unilateral aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia (BAH). The current gold standard for differentiating these conditions is adrenal venous sampling (AVS), a complex and invasive procedure. The vast majority of patients with unilateral PA who undergo adrenalectomy after successful AVS experience complete biochemical normalization2. However, there is a risk of misdiagnosing a bilateral case, in which a patient would not benefit from the removal of the gland.


Dr. Dirk Pleimes, Chief Scientific & Medical Officer at Pentixapharm AG, commented: “The FDA feedback represents a major milestone for our Company in the development of our lead diagnostic. We aim to evaluate Ga68-PentixaFor as a first-in-class, non-invasive and accurate alternative to adrenal venous sampling, offering the potential to transform diagnostic subtyping in Primary Aldosteronism and improve patient outcomes. This discussion with US regulatory authorities provided important feedback, enabling us to proceed to a US-centric registrational Phase III trial to support global authorization applications.”

 

About Pentixapharm AG

Pentixapharm is a radiopharmaceutical development company founded in 2019, with its headquarters in Würzburg, Germany. It is wholly owned by the Eckert & Ziegler Group, one of the world's largest providers of isotope technology for medical, scientific and industrial use.  Pentixapharm is committed to developing CXCR4 ligand-based first-in-class radiopharmaceutical approaches with a clear commercial pathway for diagnostic and therapeutic programs in a number of hematological and solid cancers, as well as cardiovascular and endocrine diseases.

[1] Yozamp N, Vaidya A. The Prevalence of Primary Aldosteronism and Evolving Approaches for Treatment. Curr Opin Endocr Metab Res. 2019 Oct;8:30-39. doi: 10.1016/j.coemr.2019.07.001. Epub 2019 Jul 9. PMID: 32832727; PMCID: PMC7442120.

[2] Zhou, Y., Zhang, M., Ke, S., & Liu, L. (2017). Hypertension outcomes of adrenalectomy in patients with primary aldosteronism: a systematic review and meta-analysis. BMC endocrine disorders, 17(1), 1-9.

Source: Press Release Eckert & Ziegler
Eckert & Ziegler Subsidiary Pentixapharm Receives Encouraging FDA Feedback to Initiate Phase III Trial with PentixaFor as Radiopharmaceutical Diagnostic in Primary Aldosteronism

 

Innovation / 20.06.2024
Eckert & Ziegler and UJF Open State-of-the-Art Actinium-225 Production Facility

Eckert & Ziegler Radiopharma GmbH (Eckert & Ziegler), in collaboration with the Nuclear Physics Institute of the Czech Academy of Sciences (Ústav jaderné fyziky, “UJF”), announces the grand opening of a pioneering Actinium-225 (Ac-225) production facility. This milestone, celebrated yesterday with an official ceremony featuring Czech Prime Minister Petr Fiala, marks the culmination of a longstanding partnership between Eckert & Ziegler and UJF. The facility is now close to operational readiness, and after additional testing, commercial production is slated to commence at the beginning of Q3/2024.

Currently, Ac-225-based radiopharmaceuticals are under clinical investigation for various cancers, including prostate tumors, colorectal cancer, and leukemia. A substantial increase in the demand for Ac-225 is projected over the next decade, driven by its expanding clinical applications and the promising results seen in ongoing trials. Despite its therapeutic promise, sufficient quantities of Ac-225 remain scarce.

"Eckert & Ziegler, in conjunction with UJF, has explored one of the most promising cyclotron-based production pathways for Ac-225," said Dr. Lutz Helmke, Managing Director of Eckert & Ziegler Radiopharma GmbH. "Our collaboration signifies a major leap forward in isotope production, addressing the critical shortage of this isotope poised to revolutionize modern oncology."

The newly inaugurated laboratory will leverage cutting-edge technologies, including a customized production line provided by Isotope Technologies Dresden GmbH, which represents the Plant Engineering business of Eckert & Ziegler. Radium-226, necessary for irradiation processes, will also be supplied by Eckert & Ziegler.

"Today's opening marks a significant achievement in our collaboration with Eckert & Ziegler," commented Prof. Ondřej Lebeda, Head of Department of Radiopharmaceuticals at UJF. "This new facility is a testament to our joint dedication to innovation in the therapeutic landscape for many cancer patients."

Actinium-225 has emerged as a highly promising agent in the targeted therapy of small tumors and metastases. Its high-energy cascade of alpha particles with short penetration depths allows for precise targeting of tumor cells, including difficult-to-reach micro metastases, while minimizing impact on surrounding healthy tissue.

About Eckert & Ziegler
Eckert & Ziegler SE, with more than 1,000 employees, is a leading specialist in isotope-related components for nuclear medicine and radiation therapy. The company offers a broad range of services and products for the radiopharmaceutical industry, from early development work to contract manufacturing and distribution. Eckert & Ziegler shares (ISIN DE0005659700) are listed in the TecDAX index of Deutsche Börse.
Contributing to saving lives.

About UJF
The Nuclear Physics Institute of the Czech Academy of Sciences is a public research institution that conducts research in a broad field of nuclear physics, both experimental and theoretical. Its Department of radiopharmaceuticals focuses on the investigation and production of novel medical radionuclides as well as radionuclides important for physical research.
 

Source: Press Release Eckert & Ziegler
Eckert & Ziegler and UJF Open State-of-the-Art Actinium-225 Production Facility

Innovation / 24.05.2024
Eckert & Ziegler receives “Best Managed Companies Award”

Eckert & Ziegler SE (ISIN DE0005659700) was honored with the “Best Managed Companies Award” at an award ceremony in Frankfurt am Main on May 23, 2024. With this award, Deloitte Private, UBS, Frankfurter Allgemeine Zeitung and the Federation of German Industries (Bundesverband der Deutschen Industrie e.V.) recognize outstandingly managed medium-sized companies.

Following a multi-level application process, the participating companies were assessed for their excellence in the following core areas: strategy, productivity and innovation, culture and commitment as well as finance and governance. High performance in all four areas is a prerequisite for the award. The award winners were then selected by a jury consisting of renowned representatives from business, science and the media.

“We are delighted to receive the Best Managed Companies award and consider this to be confirmation of our long-term corporate strategy. The award is also an acknowledgement of our employees, who contribute significantly to the success of our company every day with great dedication,” says Dr. Harald Hasselmann, CEO of Eckert & Ziegler SE. “This is a fantastic team achievement, which we are very excited about.”

“Eckert & Ziegler is an outstanding example of a Best Managed Company that impresses with its powerful mix of vision, productivity, innovative spirit and strong, value-oriented leadership. In addition, the company has the remarkable ability to harmonize attractive work and economic growth. It is an example of how companies can make a big difference in their region,” emphasizes Dr. Christine Wolter, Partner and Lead of Deloitte Private.

About Eckert & Ziegler
Eckert & Ziegler SE with more than 1.000 employees is a leading specialist for isotope-related components in nuclear medicine and radiation therapy. The company offers a broad range of services and products for the radiopharmaceutical industry, from early development work to contract manufacturing and distribution. Eckert & Ziegler shares (ISIN DE0005659700) are listed in the TecDAX index of Deutsche Börse.
Contributing to saving lives.

About Best Managed Companies Program
The Best Managed Companies Program is a competition and seal of quality for successful medium-sized companies. It was launched by Deloitte in Canada in the 1990s and has since been successfully introduced in more than 45 countries. Companies with an annual turnover of at least 150 million € and headquarters in Germany can apply. In addition, the companies must be medium-sized or family-owned and show successful economic development in recent years.

Press Release:
Eckert & Ziegler receives “Best Managed Companies Award”

Research, Innovation, Patient care / 22.05.2024
Captain T Cell secures seed financing round

© Captain T Cell
© Captain T Cell

Captain T Cell, a spin-off from the Max Delbrück Center, raised €8.5 million in startup funding. The startup focuses on developing T cells to target solid tumors. The funds are intended to move a new generation of T cell therapies towards the clinic.

Captain T Cell GmbH announced the successful closing of a seed financing round totaling €8.5 million. The company announced this on May 22, 2024. A syndicate of experienced life science investors including i&i Biotech Fund I SCSp, Brandenburg Kapital GmbH, and HIL-INVENT Ges.m.b.H participated in the round. In addition, the German Federal Ministry of Education and Research (BMBF), is supporting the Company, which is based in Berlin-Schoenefeld, as part of its GO-Bio program. Biotech expert Jörn Aldag has been appointed as the Chairman of the Board of Directors.

Captain T Cell is a spin-off from the Max Delbrück Center for Molecular Medicine in the Helmholtz Association. The startup builds on years of research and innovations conducted in the labs on Campus Buch and utilizes technologies developed there. Furthermore, the Max Delbrück Center provided significant financial and infrastructural support throughout the pre-seed phase and remains a close partner of the company, along with technology transfer consultancy Ascenion. Ascenion had supported the Captain T Cell team for several years before its foundation and negotiated the license agreement with Captain T Cell for the Max Delbrück Center.

The funds will be used to accelerate a new generation of T cell therapies against solid tumors towards the clinic. Captain T Cell develops first-in-class efficacy-enhanced TCR-T cells for solid tumors that are not addressed by existing therapies. In preclinical in vivo models, the Company has been able to completely eradicate aggressive tumors using these efficacy-enhanced T cells. A key technology established by the Captain T Cell team is its proprietary TCR-ALLO platform for off-the-shelf treatment of solid tumors. The tool can be expanded to a variety of cancer indications.

Dr. Felix Lorenz, CEO of Captain T Cell, said: “This successful financing round allows us to accelerate our high-potential therapies and brings us closer to providing life-saving options for patients underserved by current treatments. We are steadfast in our mission to progress our lead candidate towards the clinic and to establish our TCR-ALLO platform as a leader in off-the-shelf solid tumor therapeutics.”

Further information

www.mdc-berlin.de

Research, economic development, Patient care / 17.05.2024
Berlin-Buch goes BIO International Convention

See you in San Diego!
See you in San Diego!

The BIO International Convention attracts 15,000+ biotechnology and pharma leaders for one week of intensive networking to discover new opportunities and promising partnerships. Campus Berlin-Buch GmbH is attending this year's event, June 3-6, in San Diego.

Meet our Managing Director, Dr. Christina Quensel, at the German Pavilion at BIO 2024 and learn more about Berlin-Buch – the location of future innovation. Excellent biomedical research and one of the largest biotech parks in Germany define the Science and Technology Campus Berlin-Buch. It offers start-ups and companies in the fields of biotech and medtech state-of-the-art laboratory and office space on a gross floor area (GFA) of around 45,000 m². Recently, 14,000 m² GFA of our newly opened start-up center for biotech and medtech start-ups, the BerlinBioCube, was added to this. The inspiring life science community on-site facilitates direct exchange and joint projects.

We look forward to presenting our life science ecosystem and its opportunities to shape the future of medicine in Berlin. You can find us at booth 4217, see you there!

#BIO2024

Photo: Peter Himsel / Campus Berlin-Buch GmbH

https://bio2024.mapyourshow.com/

Research, Innovation, Patient care, Education / 15.04.2024
From cell biology to CRISPR/Cas – new knowledge for schools

Photo: Peter Himsel / Campus Berlin-Buch GmbH
Photo: Peter Himsel / Campus Berlin-Buch GmbH

The Life Science Learning Lab at the Berlin-Buch research campus offers both school students and teachers the opportunity to immerse themselves in science. This year, the facility celebrates its 25th anniversary

A white coat is more than just a protective garment. It is a symbol. Claudia Jacob, who heads the Life Science Learning Lab at the Berlin-Buch research campus, has often observed this phenomenon. Each year, some 14,000 school students and teachers visit the learning laboratory in the green setting in the north of Berlin. “They take on a different role when they put on their lab coats,” remarked Claudia Jacob. “Their curiosity seems to be awakened in an instant.” In the late 1990s, the founding director of the Max Delbrück Center, Professor Detlev Ganten, had the idea of establishing an information center to keep citizens abreast of developments in genetic engineering and biotechnology. The aim was for visitors to be able to look over the shoulders of scientists working in the lab. But Dr. Ulrich Scheller, then head of the public relations team at Campus Berlin-Buch GmbH (CBB) and now one of its managing directors, knew that just watching was not enough. The biochemist is convinced that “if you want to get people excited about research, you have to give them a chance to work with pipettes and test tubes.” And so the concept was revised.

In April 1999, after three years of renovation, the Life Science Learning Lab opened its doors as a student lab in the listed carriage house on the research campus.

More than 20 different courses

It all began with four molecular genetics experiments. Today, 25 years later, there are six laboratories in all, making it one of the largest facilities of its kind in Germany. The CBB runs the Life Science Learning Lab together with the Max Delbrück Center and the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP); they are supported by numerous sponsors and partners, including the campus-based company Eckert & Ziegler, a provider of isotope technology for medical, scientific and industrial use. Together, they offer more than 20 experimental courses covering topics such as molecular biology, cell biology, neurobiology, chemistry, radioactivity and ecology. “We are one of the few student labs in Germany where young people can even conduct experiments with CRISPR-Cas9 gene scissors,” remarked Ulrike Mittmann, scientific leader of the Molecular Biology Laboratory. Since molecular biology involves working with cells and pathogens or genetically modifying organisms, strict safety regulations apply. Schools, unlike the Life Science Learning Lab, cannot adhere to such strict regulations. As a result, the facility is a vehicle for exposing young people to current research topics.

Something for everyone

The Forschergarten at the Life Science Learning Lab also caters to young children of elementary school and kindergarten age. Moreover, there are working groups for school students, vacation courses, lectures and laboratory courses to prepare students for college. Teachers attend professional development sessions to learn about newly designed courses in the Life Science Learning Lab. In the “Lab meets Teacher” format, the Max Delbrück Center also offers teachers insights into current research topics and methods, such as single-cell analysis and Artificial Intelligence in biomedicine. Together with the Max Delbrück Center, the FMP and the Experimental and Clinical Research Center, the Life Science Learning Lab organizes the regional competition “Jugend forscht” Berlin-Brandenburg – most recently in February of this year. A total of 95 school students presented their projects at the Max Delbrück Communications Center and were given an insight into the research facilities and the Student Lab on the campus during the supporting program. “Fostering young talent is the primary goal of the Life Science Learning Lab,” commented Ulrich Scheller. “In addition to providing basic knowledge for all, we also support high-achieving school students to prepare them for a career in science or the life sciences sector.” After all, young talent is in short supply everywhere, including research labs. That is why it is important to encourage young people to train or study in this field, said Scheller. His co-managing director Dr. Christina Quensel added: “We want to show young people that researchers do not focus on abstract issues that no one else understands, but that their work affects society as a whole.” That is why ethical issues are on the agenda alongside the school curriculum. For example, why are animal experiments necessary, why should we be particularly cautious about stem cell therapies, and what does a genetic fingerprint reveal about a person? Both researchers and students benefit from this face-to-face interaction. “It is important that scientists occasionally come down from the ivory tower of basic research and explain their work in a way that is easy to understand,” stated Christina Quensel. “Many a scientist has chosen to change careers to teaching after such an experience.”

Parallels to soccer

To develop the course content, the Life Science Learning Lab team works closely with teachers from four partner schools in Berlin. They help the lab staff prepare cutting-edge research topics to fit the framework curriculum. “It takes a lot of effort for teachers to come to us with a class,” Ulrich Scheller explained. “They have to inform the parents, collect money and take the suburban train to Berlin-Buch. That means we have to give them something they can use for their classes.”

Anyone who has seen Claudia Jacob welcoming new students to her neurobiology class has no doubt that she manages to do just that. She has the youngsters put on special glasses and lets them play with various balls in the foyer of the Max Delbrück Communications Center. Ripples of laughter fill the room. The glasses change the angle of vision, making throwing and catching virtually impossible – this is what it feels like when our brains and nervous systems are misled. “Starting the class in this way sparks curiosity in the subject,” stated Claudia Jacob. It is much easier to understand when you experience firsthand what is about to be tested in various experiments. Biology is then no longer just a school subject, but the science that teaches us how an organism works. “It’s like soccer”, said Ulrike Mittmann, putting it in a nutshell. “Even if you can recite all the rules and know in theory that the ball has to go into the net, that doesn’t make you a world champion. The only way to become a world champion is to actually sprint across the field.”

For this reason, hands-on experience is a top priority in the Life Science Learning Lab. How much caffeine is in cola, how scented oils are extracted from plants, how long it takes for a nerve impulse to travel from the brain to the big toe – these are just some of the things students learn under the guidance of Claudia Jacob and her colleagues. At the end, they present their results to the class. The content of the course is not set in stone, and new things are being added all the time. Dr. Bärbel Görhardt, scientific leader of the Chemistry Laboratory, is currently designing two new courses: one on dyes in algae and how they can be extracted, and another on enzymes, which act as catalysts to initiate or accelerate various chemical reactions in the body.

Digitization in the laboratory

“In the future, we would like to link the activities of the Life Science Learning Lab more closely to current research on campus,” said Professor Maike Sander, Scientific Director and Chair of the Board of the Max Delbrück Center. One of the goals is to introduce students to innovative technologies such as single-cell sequencing and new imaging techniques. In addition, budding researchers are always guaranteed a place in the courses – perhaps not always in person, but in the form of short videos. In these videos, students explain their own experiments, which are not so dissimilar to those in the Life Science Learning Lab. “This allows the young people to see that their experiments are close to real research,” remarked Maike Sander. New media is also being used more extensively: for example, students can wear virtual reality goggles to see inside a human heart. “When they see a misfolded protein with their own eyes and observe the chain reaction that occurs, they can better understand how this affects the function of the heart,” explained Sander. As part of its graduate program, the Max Delbrück Center has launched a communications course in which doctoral students produce explainer videos and animations for the Life Science Learning Lab. In addition, the Max Delbrück Center plans to provide digital workbooks and teaching materials for schools. The FMP is also keen to focus more on current scientific and technological developments. “One exciting area is Artificial Intelligence, where we want to develop projects that allow students to understand the basics of AI and where we see areas of application in our research areas,” explained Professor Dorothea Fiedler, Director of the FMP. And the lab leaders of the Life Science Learning Lab would like to see more digitization of their work: for example, students could receive work instructions on tablets and store and share their results in the cloud. New media also offer great opportunities for microscopy, commented Ulrike Mittmann: “Looking at your own blood cells not just through an eyepiece, but on a large screen – and then taking the image home as a screensaver on your smartphone – that would be awesome!”

A truly worthwhile contribution

Inspiring a passion for research is important to everyone involved, including Paola Eckert-Palvarini, member of the Supervisory Board of Eckert & Ziegler SE. She initiated not only the Forschergarten, but also the Radioactivity Laboratory. “Radioactivity has a bad reputation in Germany,” remarked the radiation physicist, “out of ignorance.” She wants to put an end to that. In addition to experiments, she also passes on practical knowledge. Natural radiation is everywhere: “There is cosmic radiation from space, radioactive elements and rocks in the ground emit radiation, as do certain foods and even we humans.” This natural background radiation is not a health hazard. It is a different matter for radiation generated and used in industry and medicine, such as measuring the thickness of paper or treating cancer. But there is no reason to be afraid, the scientist explained: “Because we can measure radioactivity, we can use it wisely and protect ourselves from it.” Eckert-Palvarini also wants to explain how research works and what it takes to keep research results from disappearing into a drawer. The scientist is also an entrepreneur. “Research is not just about standing in a lab and chasing your own dream,” she stated. “It is also about putting discoveries and inventions to work for people.” That includes patents and licenses, as well as starting up companies. The students sometimes ask her lots of questions about these issues. “Of all the things I do, the student courses are the most rewarding,” remarked Eckert-Palvarini. “Afterwards, I go home feeling like I’ve really done something worthwhile.”

Future euphoria at Berlin-Buch

After 25 years in existence, the Life Science Learning Lab is now poised to grow beyond the boundaries of the research campus. In the new Education and Integration Center, to be built on the open space at Groscurthstraße 21-33 in the center of Berlin-Buch, it will operate three laboratories – “not quite as technically sophisticated as the laboratories on campus, but more suitable for families, where children can be introduced to scientific topics in a playful way,” explained Ulrich Scheller. This development places the Life Science Learning Lab in the heart of Berlin-Buch – the location of future innovation, where it will take on another task for society as a whole: Teaching people of all ages how science works. This includes showing them that it is part of normal scientific discourse for researchers to hold different views. “In research, many different paths lead to the goal,” noted Christina Quensel. “And it can happen that new knowledge turns everything we thought we knew upside down. We want to share this future euphoria with the public.” Dorothea Fiedler is of the same opinion: “We do not just want to communicate knowledge, but also to stimulate curiosity and foster the ability to apply and question scientific methods.” Claudia Jacob also considers this important – “especially in this day and age when so many skeptics of science are coming on the scene and spreading their alternative truths.” Putting on a lab coat and assuming the role of researcher can help us all to form an informed opinion.

Text: Jana Ehrhardt-Joswig / Campus Berlin-Buch GmbH

https://glaesernes-labor.de/

Research / 11.04.2024
ERC grants Berlin scientists € 2.5 million each

(From left) Gary Lewin © Pablo Castagnola / MDC; James Poulet © Felix Petermann, Max Delbrück Center
(From left) Gary Lewin © Pablo Castagnola / MDC; James Poulet © Felix Petermann, Max Delbrück Center

Neuroscientists Gary Lewin and James Poulet at the Max Delbrück Center for Molecular Medicine have won highly coveted and competitive ERC Advanced Grants to study pain and the neural mechanisms that underlie temperature perception.

The European Research Council (ERC) has awarded Max Delbrück Center neuroscientist Professor Gary Lewin his third prestigious Advanced Grant of €2.5 million over five years to study how nerves in the skin become overly sensitive to mechanical stimuli and cause chronic pain. “The research could lead to new pain medicines, which are sorely needed,” says Lewin.

The ERC has also awarded Max Delbrück Center neuroscientist Professor James Poulet a €2.5 million Advanced Grant to study the relationship between core body temperature in mammals and their perceptions of external temperature. Poulet’s research is basic in nature and focuses on understanding how the healthy brain functions.

Perception of mechanical pain

Gary Lewin, Group Leader of the Molecular Physiology of Somatic Sensation lab, has been researching the perception of touch and pain for over 25 years. He is a pioneer in the study of the molecular mechanisms responsible for sensing mechanical pressure on the skin – a stroke or pinch for example – in mammals.

Earlier this year, Lewin and his team reported discovering a new ion channel – pores in cellular membranes through which charged biomolecules pass through to generate the electrical activity of cells. The ion channel, called Elkin1, is present in sensory endings in the skin. It plays an essential role in transmitting the sense of touch via nerve fibers to the brain. The study was published last month in the journal “Science.”

With his new Advanced Grant, Lewin now aims to use proteomic techniques that quantify all proteins in single cells to identify ion channels in skin involved in transmitting the sense of pain. “One of the approaches we want to take is to compare the proteomes of cells that transduce these persistent mechanical stimuli to cells that don't,” Lewin explains.

Hypersensitive nerves cause many types of chronic pain syndromes, says Lewin. For example, pressure sensitive nerve fibers may become hypersensitive to mechanical stimuli causing painful sensations to the slightest touch. “We want to find the distinctive molecules that are exclusively involved in the transduction of persistent mechanical painful stimuli,” he adds.

The research could lead to new types of pain treatments. It has been decades since a new pain medication has been introduced to the market, says Lewin, who developed an antibody-based pain treatment 28 years ago. The antibody was never marketed for use in humans but is now the basis of a medication given to dogs and cats suffering from chronic arthritis pain. Moreover, many existing pain medications do not provide sufficient relief for people suffering from chronic pain, he adds.

Lewin is thrilled to be among the selected awardees: “I’m very happy. It's so gratifying that the ERC felt that our project was both interesting and new, to fund me for a third time.”

Maintaining a healthy body temperature

How the brain perceives different types of sensory stimuli is a fundamental, but unsolved, problem in neuroscience. It has long been thought that the brain regulates internal body temperature and senses external temperatures via separate networks of neuronal cells, explains James Poulet, Group Leader of the Neural Circuits and Behavior lab. But Poulet’s research suggests this view is too simplistic.

In a research paper published in the journal “Nature” last year, Poulet and his colleagues identified the primary cortical representation of temperature, a “thermal cortex,” in a posterior region of the insular cortex. This region not only responds to external temperature, but may also compare core temperature with skin temperature to create a signal by which the brain perceives the difference between the two.

“Rather than being completely separate systems, we think that brain networks that control our core physiology and those that sense the environment communicate closely with each other,” Poulet says.

With his Advanced Grant, Poulet and his colleagues will compare human and mouse, which are warm-blooded, to naked mole-rats, which are cold-blooded, to identify the cellular networks that integrate sensory and core body-state information. The researchers plan to use a combination of techniques that include neural recordings and anatomical tracing, which identifies connections between brain areas.

Poulet’s lab also plans to study individual differences in core body temperature and how they contribute to differences in perception of external temperature – a phenomenon that may explain why one person might feel the need to wear a jacket when the outside temperature is 15 degrees Celsius, while another is comfortable in a T-shirt.

Although the research will have implications for diseases that involve disrupted physiology, Poulet is more focused on studying how the brain works. “Understanding the healthy brain is how we're going to solve brain diseases in the long term,” he says.

Poulet is “happily surprised and excited,” at having won an Advanced Grant. “It's a real honor.”

www.mdc-berlin.de

Research / 09.04.2024
The Protein Expert

Fan Liu (on right side) received the Mattauch-Herzog Sponsorship Award in March 2024, presented by the German Society for Mass Spectrometry (DGMS). © Jürgen Gross
Fan Liu (on right side) received the Mattauch-Herzog Sponsorship Award in March 2024, presented by the German Society for Mass Spectrometry (DGMS). © Jürgen Gross

Prof. Dr. Fan Liu from the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) has recently received several awards for her contributions to the field of cross-linking mass spectrometry. The scientist is dedicated to better understanding the interactions between proteins at the cellular level. Additionally, she is developing methods and standards to refine this complex and indispensable technology for many research questions, making it more broadly applicable.

A lot is already known about the processes in human cells, but this knowledge is insufficient to understand, for example, how neurodegenerative diseases originate and can be cured. "To counteract diseases, we first need to know exactly how the cell functions in its normal state," says FMP researcher Prof. Dr. Fan Liu.

The biologist specializes in analyzing the interactions of proteins in cells. Such protein-protein interactions (PPI) underlie nearly all cellular processes. Deciphering them is crucial to understand the regulatory mechanisms of the cell under physiological and pathological conditions. Fan Liu and other researchers worldwide use cross-linking mass spectrometry (XL-MS) for this purpose. It is the only technology currently available that can both reveal the identities of interacting proteins and localize their binding interfaces. Additionally, XL-MS provides information about the three-dimensional structures of proteins.

Since 2017, Fan Liu has been the head of the "Structural Interactomics" research group and the Mass Spectrometry technology platform at FMP, and she also holds a professorship for Structural Interactomics at the Charité. She is working on developing new XL-MS methods and applying them to highly complex biological samples. Her goal is to gain more comprehensive insights into the naturally occurring three-dimensional structures and interactions of proteins in a cell, to better understand its general biological state and the cellular processes that are currently active.

Until a few years ago, XL-MS experiments were limited to simple mixtures of purified proteins, but they can now provide deep insights into the cellular proteome and interactome – the totality of proteins and PPI within a cell. Fan Liu has made significant contributions to this dramatic improvement: "I have developed several key methods for proteome-wide XL-MS studies and new applications that enable unprecedented insights into various complex biological systems," she says. This includes a workflow that significantly accelerates the identification of thousands of cross-links in intact human cells, with a much larger number of proven PPIs. Fan Liu and her team have also developed approaches for standardization and quality assurance in XL-MS, as well as software solutions for automatic analysis and visualization of XL-MS data.

For these diverse achievements, Fan Liu received together with Dr. Jonas Warneke from the University of Leipzig the Mattauch-Herzog Sponsorship Award in March 2024, presented by the German Society for Mass Spectrometry (DGMS) and endowed with 12,500 euros. "I am very pleased that my work in the field of XL-MS has been recognized. My goal is to provide better access to cellular data across numerous biological fields and to translate this information into useful applications," says Fan Liu about the award.

Back in January, the FMP researcher had already been named one of the "2024 Rising Stars in Proteomics and Metabolomics" by the Journal of Proteome Research (JPR) of the American Chemical Society. A few weeks later, she and Patrik Verstreken from the Leuven Brain Institute received a Collaborative Pairs Pilot Project Award from the Neurodegeneration Challenge Network (NDCN) of the Chan Zuckerberg Initiative. The researchers aim to study the interactions between synaptic proteins of hibernating animals to better understand how hibernators counteract the permanent loss of synapses. Through this, Fan Liu and Patrik Verstreken hope to gain insights into how synapse loss in human neurodegenerative diseases can be mitigated.

Source: Press Release at the website of the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP): The Protein Expert

Innovation / 21.03.2024
Eckert & Ziegler Receives MDR Certification for Prostate Seeds, Paving the Way for Long-term Supply

Eckert & Ziegler BEBIG GmbH, subsidiary of Eckert & Ziegler SE with focus on brachytherapy solutions for the treatment of prostate cancer as well as eye and brain tumors, obtained the MDR certificate for its proprietary prostate seeds from DEKRA Certification B.V. as one of the first companies in its market. This important milestone guarantees a high level of patient safety and the long-term availability of the seeds within the EU.

The Medical Device Regulation (MDR) is a European Union directive (EU 2017/745) with the aim of improving the quality of medical devices and increasing patient safety. Prostate seeds have been manufactured and internationally marketed by Eckert & Ziegler since 1999 and contribute several million euros in annual sales to the Eckert & Ziegler Group's earnings.

"We are very pleased about the first successful MDR certification. It confirms that our quality management system and the prostate seeds comply with the stringent requirements and that we can continue to provide them to our users as a safe medical device. This is not only a significant achievement for the distribution of our brachytherapy products, but for the entire Eckert & Ziegler Group," explained Katrin Antonenko, Managing Director of Eckert & Ziegler BEBIG GmbH. "We are already working intensively on the certification of our other medical products in order to ensure patient care for further applications in the long term. We will benefit from the experience gained from the successful approval process."

In prostate seed brachytherapy, pinhead-sized implants are inserted directly in the prostate. Due to the proximity of the radiation source to the tumor, the surrounding healthy tissue is spared as much as possible in this minimally invasive radiation procedure.

About Eckert & Ziegler.
Eckert & Ziegler SE with more than 1.000 employees is a leading specialist for isotope-related components in nuclear medicine and radiation therapy. The company offers a broad range of services and products for the radiopharmaceutical industry, from early development work to contract manufacturing and distribution. Eckert & Ziegler shares (ISIN DE0005659700) are listed in the TecDAX index of Deutsche Börse

Source: Press Release
Eckert & Ziegler Receives MDR Certification for Prostate Seeds, Paving the Way for Long-term Supply

Innovation / 19.03.2024
Eckert & Ziegler Completes Change of Legal Form to SE

Eckert & Ziegler Strahlen- und Medizintechnik AG (ISIN DE0005659700) today completed its change of legal form to a Societas Europaea (SE) with entry in the company's commercial register and will in future operate as Eckert & Ziegler SE.

Eckert & Ziegler SE has a dualistic management system consisting of a management body (Executive Board) and a supervisory body (Supervisory Board). The corporate bodies of Eckert & Ziegler SE are therefore, as at Eckert & Ziegler Strahlen- und Medizintechnik AG, the Executive Board, the Supervisory Board, and the General Meeting.

All shareholders hold the same number of shares in Eckert & Ziegler SE as they did in Eckert & Ziegler Strahlen- und Medizintechnik AG before the change of legal form. The number of no-par value shares issued remains unchanged. Trading will continue seamlessly. The conversion in the shareholders' securities accounts will take place automatically. The previous ISIN DE0005659700, WKN 565970 and the ticker symbol EUZ will remain unchanged.

 

About Eckert & Ziegler.
Eckert & Ziegler SE with more than 1.000 employees is a leading specialist for isotope-related components in nuclear medicine and radiation therapy. The company offers a broad range of services and products for the radiopharmaceutical industry, from early development work to contract manufacturing and distribution. Eckert & Ziegler shares (ISIN DE0005659700) are listed in the TecDAX index of Deutsche Börse.

Source: Press Release Eckert & Ziegler AG
Eckert & Ziegler Completes Change of Legal Form to SE

Research / 01.03.2024
A new channel for touch

Sampurna Chakrabarti, Research Group of Gary Lewin, at the mikrocope. Katharina Bohm, Max Delbrück Center
Sampurna Chakrabarti, Research Group of Gary Lewin, at the mikrocope. Katharina Bohm, Max Delbrück Center

Touch is a fundamental, yet scarcely understood, sense. Now, the team led by Gary Lewin at the Max Delbrück Center has discovered a second ion channel associated with touch perception. Elkin1 could be a target for pain therapy, the team writes in “Science”.

Every hug, every handshake, every dexterous act engages and requires touch perception. Therefore, it is essential to understand the molecular basis of touch. “Until now, we had known that the ion channel – Piezo2 – is required for touch perception, but it was clear that this protein alone cannot explain the entirety of touch sensation,” says Professor Gary Lewin, head of the Molecular Physiology of Somatic Sensation Lab at the Max Delbrück Center.

For over 20 years Lewin has been studying the molecular basis of the sensation of touch. He and his team have now discovered a new ion channel, named Elkin1, that plays a vital role in touch perception. This is only the second ion channel implicated in the touch perception. It is likely that the protein is directly involved in converting a mechanical stimulus, such as light touch, into an electrical signal. When Elkin1 is present, the receptors in the skin can transmit the touch signals via nerve fibers, to the central nervous system and brain. The researchers have published their findings in the journal “Science.”

Lewin’s team came across Elkin1 a few years ago while investigating a malignant melanoma cell line. The researchers had found that the protein is required for sensing mechanical forces by these highly motile cancer cells. “Now we wanted to determine whether the same protein also plays a role in touch sensation” says Lewin.

Lack of Elkin1 reduces touch sensitivity

The researchers bred genetically modified mice that lacked the Elkin1 gene. They then conducted simple behavioral experiments that involved lightly brushing a cotton swab against the rodents’ hind paws. “Usually, normal mice react to the cotton swab 90% of the time,” says Lewin. “In contrast, mice lacking Elkin1 only reacted half of the time, indicating touch insensitivity”. Importantly, the rodents’ reaction to non-mechanical stimuli like temperature was not affected.

At the neuronal level, Dr. Sampurna Chakrabarti, a scientist in Lewin’s team, used the patch clamp method to record the electrical activity of sensory neurons in response to poking of the neuronal membrane. “Around half of the neurons in genetically modified mice lacking Elkin1 didn’t respond to mechanical stimuli, and no signal transmission occurred,” says Chakrabarti. Further experiments confirmed that there were no signals relayed from the neuron’s receptor ending in the skin, on the first leg of the signals journey from skin to the spinal cord and brain. Furthermore, their Australian collaborators in the lab of Professor Mirella Dottori in the University of Wollongong tested whether Elkin1 in necessary for touch transduction in human sensory neurons grown in a petri dish from stem cells. Their findings also strongly suggest that Elkin1 could play a major role in human touch perception.

The researchers assume that during normal signal transmission, Elkin1 and Piezo2 share roles in touch perception. They have also found evidence that Elkin1 may play a part in the transmission of painful mechanical stimuli. “If this is confirmed to be the case, we will have not only identified a second ion channel with an indispensable role in normal touch perception, but also a new potential target for treating chronic pain,” says Lewin.

Text: Stefanie Reinberger

Source: Press Release Max Delbrück Center
A new channel for touch

Innovation / 08.02.2024
FyoniBio, Alder Therapeutics, and BioLamina enter Consortium Grant Agreement to Propel Recombinant Human Laminin Development for Clinical Applications

Berlin, Germany, and Stockholm, Sweden, February 07, 2024 — FyoniBio, a contract development organization (CDO) specializing in customized cell line and process development has partnered with BioLamina, a biotech company renowned for its expertise in extracellular laminin-based cell biology and development of laminins as tools for cell culture, and Alder Therapeutics, a virtual preclinical allogeneic stem cell therapy development company. The consortium will advance the development of laminins for clinical applications.

As part of the grant-funded consortium, BioLamina and FyoniBio have executed a Master Service Agreement under which FyoniBio will use its long-standing expertise in cell line development in a variety of different mammalian cell systems, including human cell lines, to develop production clones for a couple of BioLamina’s full-length human recombinant laminins.

"FyoniBio is honored to collaborate with BioLamina and Alder Therapeutics in this transformative project. The synergy between FyoniBio's advanced human cell line development capabilities, BioLamina's legacy and significant impact on cell culture standardization and quality by their laminins as substrates, and Alder’s innovative cell therapy development platform will make for a fruitful collaboration. This is the latest step in our collective commitment to help advancing cell therapies”, commented Dr. Lars Stöckl, Managing Director at FyoniBio. “

“The collaboration between BioLamina, FyoniBio and Alder Therapeutics, supported by the secured grant funding, will enable us to combine the specific expertise of all three parties, which we expect will result in a further pushing of the boundaries of cell therapy”, says Veronica Byfield Sköld, CEO of BioLamina

“Both FyoniBio and BioLamina are renowned for their complex protein production expertise, so partnering with them is a fantastic opportunity,” commented Dr. Kristian Tryggvason, CEO at Alder therapeutics. “This collaboration will provide us with additional support for our manufacturing process, so we can help treat the Retinitis Pigmentosa patients”, commented Dr. Kristian Tryggvason, CEO at Alder therapeutics.

For more information about FyoniBio, please visit fyonibio.com. For more information about BioLamina, please visit biolamina.com. To find out more about Alder Therapeutics, please visit aldertx.com.

About FyoniBio GmbH

FyoniBio’s ISO-9001 certified service portfolio covers the development chain from cell line development, process development and in-depth analytical characterization, including bioassays and clinical sample monitoring under GCLP. FyoniBio’s expertise builds on the long-standing experience of their scientists who have developed various cell lines and processes which entered late-stage clinical trials. FyoniBio`s customized approaches enable rapid, high-titer cell line development in various mammalian host cell lines specialized in meeting individual product requirements. Besides the CHOnamite® platform, FyoniBio provides the human GEX® platform, which is particularly suited for recombinant proteins with complex glycan structures. Furthermore, FyoniBio is highly skilled in mass spectrometry based in-depth analytical characterization of biopharmaceuticals and offers the whole package of clinical sample analysis from assay establishment, validation and measurement of clinical samples under GCLP.

All services are established according to the internal quality management system to assure compliance with international ISO standard and meeting international GMP standards.

About BioLamina AB

BioLamina is a Swedish biotechnology company founded in 2009, built on a strong scientific foundation in cell biology and with a legacy in extracellular matrix biology. BioLamina develops, manufactures and commercializes human recombinant laminin substrates to better reflect a biorelevant environment for cultured cells in order to maintain control, gain protocol precision and create safe cells for therapy.

With its expansive portfolio of cell culture matrices, BioLamina has established itself as a key player in advancing cell therapy worldwide, recognized for its premium products, deep scientific competence and state-of-the-art service.

About Alder Therapeutics

Alder Therapeutics is a biotechnology company on a mission to cure the incurable by harnessing the potential of pluripotent stem cell-developed therapies. Through our unique cell therapy development philosophy, we overcome the challenges of traditional development approaches, embedding risk reduction and commercial-mindedness at the core of cell therapy programs.

We have two promising allogenic stem cell therapies in the pipeline, both with preclinical proof of concept data. Our flagship program is a retinal cell therapy aiming to revolutionize treatment of Retinitis Pigmentosa.

Quelle: FyoniBio GmbH

www.fyonibio.com

Innovation / 23.01.2024
Eckert & Ziegler and Full-Life Technologies Sign Actinium-225 Supply Agreement for Next Generation Radiopharmaceuticals

Eckert & Ziegler (ISIN DE0005659700, SDAX) and Full-Life Technologies (Full-Life), a clinical stage, fully integrated global radiotherapeutics company today announced they have entered into an agreement for the supply of Actinium-225 (Ac-225). The agreement provides Full-Life with access to Eckert & Ziegler's high-purity Actinium-225, a radionuclide for use in developing the next generation of therapeutic radiopharmaceuticals.

Ac-225 has emerged as a highly promising active agent for the treatment of cancer. The radioisotope releases potent alpha particles with high energy and short penetration depths, allowing for precise targeting of tumor cells, including hard-to-reach micro-metastases, while minimizing impact on surrounding healthy tissue. Based on its potential, clinical and industry experts expect a substantial increase in Ac-225 demand in the coming decade.

“We are delighted to have forged a supply collaboration with Full-Life Technologies, dedicating ourselves to facilitating their journey in clinical development,” said Dr Harald Hasselmann, CEO of Eckert & Ziegler. “Historically, limited Ac-225 supply has impeded progress in both clinical research and commercial applications. With the establishment of our new Ac-225 production facility, we aim to significantly increase access to this important radionuclide, with ramp up at the new facility occurring in the second half of the year.”

Ac-225 constitutes an essential element within our portfolio of therapeutic compounds, including our lead candidate, Ac-FL-020 for the treatment of metastatic castration-resistant prostate cancer,” stated Philippe van Put, General Manager of Full-Life Technologies Europe. “Securing access is imperative for advancing our development and clinical research efforts. Eckert & Ziegler brings great expertise and more than three decades of experience as a radioisotope specialist in support of our ambitious development initiatives.”

About Eckert & Ziegler
Eckert & Ziegler Strahlen- und Medizintechnik AG with more than 1.000 employees is a leading specialist for isotope-related components in nuclear medicine and radiation therapy. The company offers a broad range of services and products for the radiopharmaceutical industry, from early development work to contract manufacturing and distribution. Eckert & Ziegler shares (ISIN DE0005659700) are listed in the SDAX index of Deutsche Börse.
Contributing to saving lives.

About Full-Life Technologies
Full-Life Technologies Limited ("Full-Life") is a fully integrated global radiotherapeutics company with operations in Belgium, Germany, and China. We seek to own the entire value chain for radiopharmaceutical research & development, production & commercialization in order to deliver clinical impact for patients. The Company plans to attack core issues affecting radiopharmaceuticals today through innovative research that targets the treatments of tomorrow. We are comprised of a team of fast-moving entrepreneurs and scientists with a demonstrated track record in the life sciences, as well as radioisotope research and clinical development.

Source: Press Release EZAG
Eckert & Ziegler and Full-Life Technologies Sign Actinium-225 Supply Agreement for Next Generation Radiopharmaceuticals

Research / 18.01.2024
Third ERC Grant for Gaetano Gargiulo

Dr Gaetano Gargiulo (Photo: David Ausserhofer, Max Delbrück Center)
Dr Gaetano Gargiulo (Photo: David Ausserhofer, Max Delbrück Center)

Cell-based immunotherapies, particularly lab-produced immune cells known as CAR T cells, show promise in treating various cancers. But how do we produce effective ones? Gaetano Gargiulo from the Max Delbrück Center will develop a novel screening tool, supported by an ERC Proof of Concept Grant.

Dr Gaetano Gargiulo, head of the Molecular Oncology Lab at the Max Delbrück Center, and his team are working on a screening tool that distinguishes between cell states of CAR T cells when they are either very effective at killing cancer cells or exhausted. The European Research Council is supporting the initial steps toward commercialization with a Proof of Concept (PoC) Grant of €150,000. Gargiulo is among 240 researchers from across Europe who received such funding in last year’s three competition rounds. The ERC announced 102 PoC grants on January 18th, paving the way for the researchers to translate their pioneering findings into broadly applicable solutions.

After a Starting Grant in 2016 and a Proof of Concept Grant in 2022, this is his third ERC Grant. “I am privileged to be continuously supported by European Research Council,” says Gargiulo. “We were blessed with an ERC Starting Grant in the past and created a very flexible technology to study how cancer cells change their state to become worse. We realized that we can also use it to improve immune cells that we genetically engineer to combat cancer. This funding instrument gives us the momentum to tap into this lead.”

Some T cells fall short – for many reasons

CAR T-cell therapies are often a last resort for patients with certain types of leukemia and lymphoma who do not respond to standard treatments – and new versions of these cell-based immunotherapies are being developed for solid tumors as well. This technique involves taking immune cells (T cells) from the patient and equipping them with a chimeric antigen receptor (CAR) in the laboratory. The CAR acts like a tiny antenna, patrolling the body’s cells for specific features on the cancer cells (antigens). Once the CAR T cells are re-introduced back into the patient’s body, they begin to detect and destroy cancer cells with the antigen that fits their new receptors.

However, stumbling blocks such as the intricate manufacturing process, excessive exposure to antigens, the harsh environment within a tumor and in its immediate neighborhood can result in T cells that fall short, hampering their efficacy against both blood cancers and solid tumors. The manufacturing process itself is also very expensive, on the order of hundreds of thousands of Euros, so even minimal modifications to the process that might make it more efficient in producing effective CAR T cells could make this approach more sustainable and available to more patients.

Screening and reversing dysfunction

With the ERC Proof of Concept Grant, the Gargiulo Lab aims to create and validate a novel tool to improve the quality of T cell products in the lab. It's called SynT, a synthetic reporter system designed to indicate different cell states that either render T cells dysfunctional or that represent a potent “serial killer” mode. These cell states are detected by lab-engineered segments of DNA that switches a fluorescent protein on or off (named synthetic locus control region or sLCR). Depending on which sLCR is turned on, the cells glow in a different color when observed under a fluorescence microscope. With a fast microscope and robotic platform, the team can test hundreds of conditions in parallel, to find those that enhance the “serial killer” mode.

“This screening can help us to pinpoint signaling pathways or pharmacological agents that can boost functional CAR T cells and reverse dysfunction. SynT will help us better understand the process of cell bioengineering that underlies cell therapy for cancer, and potentially to improve the manufacturing to increase activity and reduce costs,” says Gargiulo. “Ultimately, these advances can make CAR T cell therapies even more effective.”

Engineered immune cells (shown as small round magenta dots) surrounding brain tumor cells with distinct identities as revealed by a dual synthetic DNA-driven fluorescent reporters (blue & yellow). Photo: Matthias Jürgen Schmitt, Gargiulo Lab, Max Delbrück Center

Source: Press Release Max Delbrück Center
Third ERC Grant for Gaetano Gargiulo

Research, Innovation, Patient care / 09.01.2024
"More Entrepreneurial Thinking in Research"

Photo: Peter Himsel / Max Delbrück Center
Photo: Peter Himsel / Max Delbrück Center

Interview with Professor Maike Sander, Scientific Director of the Max Delbrück Center

How does the Campus Berlin-Buch promote or nurture the successful commercialization of life science knowledge?

At Campus Buch, we do fundamental research in various disciplines, all related to biomedical discovery. This includes research at the Max Delbrück Center, the FMP, but also at the Charité – Universitätsmedizin and the Berlin Institute of Health (BIH). This ecosystem serves as an intellectual incubator for ideas, including medical applications. We have already seen numerous start-ups emerge from basic discoveries at Campus Buch. Much of this work has been collaborative and cross-institutional. The most prominent example is, of course, T-knife which originated as a joint project between the Max Delbrück Center and Charite. T-knife develops T-cell therapies for solid tumors using tailored T-cell receptors. The company started here on Campus Buch and now has a branch in San Francisco. But T-knife is not the only company that has been launched based on research at Campus Buch. Recent spin-offs include MyoPax and CARTemis Therapeutics, both deeply rooted in institutions such as the Max Delbrück Center and the Charité. MyoPax combines cell and gene technology to regenerate and restore muscle function after an accident, in cases of muscle atrophy, or in muscular dystrophy. CARTemis, on the other hand, is pioneering cell-based immunotherapies for cancers that were previously considered untreatable. Campus Buch provides the space and facilities to house these emerging companies in close proximity to the labs that initiated these innovations. This proximity is crucial, especially in the early phase of starting a company.

You are referring to the new BerlinBioCube start-up incubator on Campus Buch. How can it contribute to knowledge transfer and networking between science and business?

The BerlinBioCube enriches the campus in two significant ways. First, it provides space for emerging companies; the impact of having this space next to institutions like the Max Delbrück Center, FMP, Charité, BIH cannot be underestimated. Second, it brings an entrepreneurial mindset to our campus. Scientists are typically not trained to start companies, and there is little knowledge of what investors are looking for or what it will eventually take to bring a new diagnostic or therapy to market. By hosting joint networking events between the scientific institutes on the campus and budding companies in the BerlinBioCube, we can learn from each other and bring more business acumen to the scientists in our institutions.

How can we make spin-offs from research institutions even more attractive?

Researchers are often concerned that founding a company could distract them from their scientific pursuits. Examples in the US and Israel show that this does not need to be so. Often the students and postdocs launch the companies, while the PI moves on to work on the next innovation with the next generation of trainees. As institutions, we can support commercialization by providing additional resources to help PIs adapt their technologies and discoveries to launch a start-up. So, it doesn’t have to be a choice between launching a company or continuing the research.

What can we learn from startup hubs in the USA and Israel/Tel Aviv?

What these hubs have, and what we need to build more of in Berlin and Germany, is a close exchange between scientists, entrepreneurs, and investors. The successful hubs in the US and Israel have a functioning ecosystem where people from these different worlds meet regularly. In our science institutions, we need to bring more of an entrepreneurial mindset to science and scientists. In the U.S., many scientists now earn a dual PhD/MBA. The younger generation of scientists wants to create societal value from their discoveries through commercialization. We can build that here by offering training through our graduate school and other channels. Having BerlinBioCube on the campus will also be a huge asset, because it will nucleate the exchange. Another important component is, of course, investor money. We need to come together as institutions to show international investors how much we have to offer. Science in Berlin and Germany is very strong, so it’s most definitely not a matter of a lack of excellence at the beginning of the pipeline.

How can research benefit even more from proximity to biotech companies?

Networking events will be a huge amplifier. Ultimately, it’s all about people learning from each other and inspiring each other.

 

Research, Innovation, Patient care / 08.01.2024
Eckert & Ziegler and ARTBIO Announce Manufacturing and Supply Partnership for Lead-212 Conjugates

Berlin, Germany and Cambridge, Mass., – 8 January 2024 – Eckert & Ziegler (ISIN DE0005659700, SDAX) and ARTBIO, Inc. (ARTBIO), a clinical-stage biotechnology company specializing in the development of a new class of alpha radioligand therapies (ARTs), have entered into a strategic manufacturing and supply agreement. Under the collaboration Eckert & Ziegler will support ARTBIO to establish manufacturing and delivery of its pipeline therapies using its proprietary AlphaDirectTM Lead-212 (Pb-212) isolation technology.

The collaboration aims to expedite the development of Lead-212 based alpha radioligand therapies, starting with the clinical development of ARTBIO’s lead asset of AB001 in prostate cancer. Initially focussing on the US market and utilizing Eckert & Ziegler’s facilities in Boston, both companies plan to evaluate a global operations expansion at a later stage. Besides the US, Eckert & Ziegler’s global CMO service network includes manufacturing sites in Berlin, Germany and Jintan, China.

The radioisotope Lead-212 is an alpha precursor used as an active substance in cancer treatment. As part of a radiopharmaceutical product, the radioisotope enables precision treatment of tumor cells, while minimizing the damage to healthy adjacent tissue. With several studies ongoing, Pb-212-labeled compounds represent one of the most promising therapeutic approaches in nuclear medicine.

"We are excited to collaborate with ARTBIO in this transformative venture,” stated Dr. Harald Hasselmann, CEO of Eckert & Ziegler. ”By combining Eckert & Ziegler's expertise in radiopharmaceutical manufacturing with ARTBIO's innovative approach to therapeutic solutions, we are poised to make substantial progress in advancing Lead-212 based alpha therapies."

"We are pleased to partner with Eckert & Ziegler to expand our distributed manufacturing network in order to reliably and efficiently deliver alpha radioligand therapies to patients," said Conrad Wueller, Director, Strategy and Operations at ARTBIO. "Eckert & Ziegler's vast experience and global footprint in radiopharmaceutical manufacturing and distribution will be critical as we advance our pipeline and aim to get our therapeutic candidates to people who need them most."

About Eckert & Ziegler
Eckert & Ziegler Strahlen- und Medizintechnik AG with more than 1.000 employees is a leading specialist for isotope-related components in nuclear medicine and radiation therapy. The company offers a broad range of services and products for the radiopharmaceutical industry, from early development work to contract manufacturing and distribution. Eckert & Ziegler shares (ISIN DE0005659700) are listed in the SDAX index of Deutsche Börse.
Contributing to saving lives.

About ARTBIO
ARTBIO is a clinical-stage radiopharmaceutical company redefining cancer care by creating a new class of alpha radioligand therapies (ARTs). The unique ARTBIO approach selects the optimal alpha-precursor isotope (Pb-212) and tumor-specific targets to create therapeutics with the potential for highest efficacy and safety.  The company's AlphaDirectTM technology, a first-of-its-kind Pb-212 isolation method, enables a distributed manufacturing approach for the reliable production and delivery of ARTs. ARTBIO is advancing three pipeline programs with lead program AB001 currently in first in human trials. ARTBIO is shaped by a long-standing scientific legacy with nearly a century of pioneering work in radiation therapy conducted at the University of Oslo and Norway's Radium Hospital.

Research, Innovation, Patient care / 02.01.2024
New agent regulates serotonin production

Radoslaw Wesolowski (left), Michael Bader (center) and Dr. Edgar Specker have teamed up to develop a potential therapeutic agent that influences serotonin levels. © Peter Himsel, Campus Berlin-Buch GmbH
Radoslaw Wesolowski (left), Michael Bader (center) and Dr. Edgar Specker have teamed up to develop a potential therapeutic agent that influences serotonin levels. © Peter Himsel, Campus Berlin-Buch GmbH

Diseases can emerge when the body’s production of serotonin is out of whack. Researchers led by Michael Bader from the Max Delbrück Center have discovered a therapeutic agent that brings down high levels of this hormone. Their start-up, Trypto Therapeutics, aims to develop the drug for the market.

Serotonin makes you feel good. This neurotransmitter known as the “happiness hormone” regulates mood, sleep, and appetite. It also plays a key role in the gastrointestinal tract, where it is involved in regulating intestinal movement and the release of fluids that are important for the digestion and absorption of nutrients.

But too much serotonin causes health problems. An oversupply of the hormone can disrupt normal bodily functions and trigger various diseases. Professor Michael Bader and Dr. Edgar Specker have developed a drug that specifically lowers serotonin levels. Bader leads the Molecular Biology of Peptide Hormones Lab at the Max Delbrück Center, while Specker heads the Compound Management Core Facility at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP). “We have now founded Trypto Therapeutics to bring our new therapeutic agent to the market,” says Bader. Along with the two scientists, biotech entrepreneurs Dirk Pleimes and Dr. Radoslaw Wesolowski are also involved in the new company. Max Delbrück Center and the FMP have an equity stake in the spin-off.

Stopped by the blood-brain barrier

Scientists don’t know exactly why serotonin production gets out of whack. An exception is carcinoid syndrome, a tumor disease in which hormone-producing cells release inordinate amounts of serotonin. Carcinoid syndrome is often associated with diseases like pulmonary hypertension, intestinal diseases, and heart valve fibrosis. However, they can also occur in patients without carcinoid syndrome. As different as these diseases are, elevated serotonin is involved in the development of all of them.

This is where the molecule that Bader and Specker discovered and further developed in the FMP’s compound library comes into play. It is called TPT-004 and inhibits an enzyme found in gastrointestinal tract cells, called tryptophan hydroxylase (TPH), that plays a role in serotonin synthesis. Lower TPH activity means less serotonin circulating through the body. The researchers showed that the administration of TPT-004 improves the health of rats with pulmonary hypertension. They were also able to prove that this molecule cannot cross the blood-brain barrier in mice. This is important because serotonin is also produced in the neurons – a process that should not be blocked because the brain requires the neurotransmitter to function properly.

Venture capital needed to move forward

A great deal of funding has gone into developing the TPH inhibitor so far – through the Max Delbrück Center’s Pre-GoBio funding scheme, through various lines of funding from the German Federal Ministry of Education and Research (BMBF) and, most recently, through the Max Delbrück Center’s SPOT spin-off support program. “We’ve received around €4.5 million in total,” says Bader. “But public third-party funding is not enough to take the next step. We need venture capital to do this. That’s why we founded Trypto Therapeutics.”

The scientists first plan to develop a method for producing their therapeutic agent in pure form in sufficient quantities so that it can be used in human clinical trials. They will also carry out a toxicity study in order to investigate the risks and possible side effects of the compound. Only then will it be possible to conduct a phase I clinical trial on a small group of healthy volunteers. “If we successfully complete the phase I trial, we will then decide whether to conduct a subsequent phase II study or sell the whole thing,” says Bader. The researchers initially want to test the drug on patients with pulmonary hypertension. If this works, they want to examine whether TPT-004 helps treat other diseases associated with elevated serotonin levels. Their development pipeline also includes new inhibitors for other enzymes.

Text: Jana Ehrhardt-Joswig

Source: Joint press release of the Max Delbrück Center and the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP).
New agent regulates serotonin production

economic development / 14.12.2023
Charles River Finalizes Agreement with CELLphenomics, Expanding 3D In Vitro Services for Cancer Therapy Drug Screening

CELLphenomics’ PD3D® tumor model platform will expand Charles River’s portfolio of 3D in vitro testing services

WILMINGTON, Mass. & BERLIN--(BUSINESS WIRE)--Dec. 12, 2023-- Charles River Laboratories International, Inc. (NYSE: CRL) today announced that it has entered into an agreement with CELLphenomics, a service-based biotechnology company that is using 3D hydrogel technology to advance the understanding of the tumor microenvironment and predict therapeutic efficacy. This enhanced offering will provide Charles River clients with access to CELLphenomics’ proprietary 3D tumor model platform, PD3D®, expanding Charles River’s 3D in vitro testing services to further optimize oncological approaches for its clients.

CELLphenomics’ core competency is the establishment and cultivation of complex patient-derived 3D cell culture models (PD3D) from various solid tumor tissues. These highly reliable, well-annotated and predictive preclinical PD3D models robustly recapitulate the biological properties of the donor tissue, including key histopathological features and genomic makeup. They are a powerful tool for disease modeling, biomarker and drug discovery.

CELLphenomics’ continuously growing biobank comprises more than 500 complex in vitro models from more than 20 tumor entities, and offers the world’s largest collection of complex in vitro models of rare and ultra-rare tumors like sarcomas or thymomas.

CELLphenomics has developed a custom mid-throughput screening platform that blends complex cell culture models with advanced automation and a streamlined analysis pipeline. The proprietary, precision medicine PD3D platform offers mid-throughput efficacy testing, drug combination screening, toxicity profiling, target validation, drug sensitivity correlation with clinical response, and biomarker identification.

Charles River offers a range of cancer cell-based assays, including patient-derived xenograft (PDX) assays and assays representing the entire tumor microenvironment (TME), so therapies are not only tested for their effect on real patient materials, but also their interaction with the human immune systems. Leveraging CELLphenomics technology, Charles River will now have a novel in vitro option for identifying therapeutics for rare and ultra-rare disease types.

The agreement will also provide CELLphenomics access to Charles River’s genomically annotated and in vivo characterized cancer model database to develop PD3D models. The database is comprised of more than 700 tumor models, including PDX, cell lines and cell line-derived xenografts (CDX). These models have been extensively profiled for histological features, molecular data, and sensitivity to standard-of-care compounds, allowing a precise selection of suitable tumor models for preclinical anti-cancer agent testing. The biological advantages of PDX include the retention of histological and genetic characteristics of the donor tumor and the preservation of cell-autonomous heterogeneity. The merge of both biobanks will significantly increase the translational relevance of the in vitro and in vivo platforms offered by CELLphenomics and Charles River.

Approved Quotes

“The field of 3D in vitro services for oncology research is rapidly developing. We’re excited for the integration of CELLphenomics’ tumor model platform into our existing portfolio of products and services.” – Aidan Synnott, Corporate Vice President, Global Discovery Services, Charles River

“Our clients will benefit from this enhanced offering, but ultimately, our work will benefit patients who desperately need new treatments for cancer.” – Julia Schueler, PhD, Research Director and Therapeutic Area Lead, Oncology, Charles River

“This agreement allows us full access to Charles River’s impressive biobank and data. Now we can provide them with high quality models of the same genomic background through the entire preclinical development process – literally for any solid tumor type. From large high-throughput in vitro screens to selected PDX models, with Charles River as our partner, we can ensure an even more swiftly developmental process for novel anti-cancer drugs. Together, we make our customers’ compounds work.” –Dr. Christian Regenbrecht, CEO, CELLphenomics

About Charles River
Charles River provides essential products and services to help pharmaceutical and biotechnology companies, government agencies and leading academic institutions around the globe accelerate their research and drug development efforts. Our dedicated employees are focused on providing clients with exactly what they need to improve and expedite the discovery, early-stage development and safe manufacture of new therapies for the patients who need them. To learn more about our unique portfolio and breadth of services, visit www.criver.com.

About CELLphenomics
CELLphenomics establishes and cultivates complex patient-derived 3D cell culture models (PD3D®) from various solid tumor tissues. The company’s in vitro services combine wet-lab biology, automation and high throughput screening directly on patient samples to help predict responses to potential therapies, and ultimately determine which drugs or drug combinations will be most effective for specific types of cancers, visit:

www.cellphenomics.com

View source version on businesswire.com: https://www.businesswire.com/news/home/20231211345497/en/

Research, Education / 30.11.2023
What do scientists actually do in the lab?

© Marie Burns, Max Delbrück Center
© Marie Burns, Max Delbrück Center

Grizzly bears in hibernation or a pineapple in an MRI scanner – at the “Science Day” at the “Robert Havemann” high school in Berlin-Karow, researchers from the Max Delbrück Center presented students of grades 11 and 12 unusual facets of their research.

Marine, sports journalist or engineer – some students know exactly what they want to do after graduating from high school. Others still find it difficult to choose a career or field of study. To give them an insight into the world of science, researchers presented their career paths and work at the Robert Havemann high school at the end of November. Professor Thoralf Niendorf, head of the “Experimental Ultrahigh-Field MR” lab at the Max Delbrück Center, and Professor Michael Gotthardt, head of the “Translational Cardiology and Functional Genomics” lab, also participated.

Google Maps for health – only better” is how Thoralf Niendorf describes what modern imaging techniques can do for our health. A map of our body that integrates information from the anatomical to the molecular level. This data allows for conclusions regarding blood flow or metabolic processes in tissue, for example, and not only improves diagnostics, but also enables predictions about the health of the person being examined. Niendorf and his team aim to improve magnetic resonance technology and the analysis of complex data using artificial intelligence.

For testing purposes, they like to put unusual objects in the MRI scanner – such as a pineapple. But the researcher has also brought actual case studies on the heart, brain and eye and encourages the students to guess what they can see. They are fascinated by the sometimes moving images and have lots of questions. “We would like to inspire curiosity and provide information about the wide range of career opportunities in science,” says Thoralf Niendorf. Engineers, technical assistants, programmers, an efficient administration – cutting-edge research needs bright minds with different talents.

Finding reliable information

Down the hall, Michael Gotthardt shares with the students what his team is doing in the lab. The long-time mentor for young scientists analyzes cardiovascular and muscle diseases. He also works with unusual model organisms – pythons that can enlarge their hearts for a short time after devouring their prey, or grizzly bears that hardly lose any muscle mass despite hibernating for months. “If we understand which molecular processes grant these animals their characteristics, we could use the findings to improve human health,” he says.

The students are intrigued, want to know what day-to-day work in biomedical research looks like and how to become a professor. Gotthardt answers patiently and gives advice. Above all, he is interested in addressing the big questions: How does the scientific process work? How is a new drug developed? How do students find reliable information to make decisions about their own health? He wants to leave them with something that illustrates the importance of science for their own lives – as a career opportunity and beyond.

Text: Marie Burns

Research / 30.11.2023
Heart repair via neuroimmune crosstalk

© Onur Apaydin, Max Delbrück Center
© Onur Apaydin, Max Delbrück Center

Unlike humans, zebrafish can completely regenerate their hearts after injury. They owe this ability to the interaction between their nervous and immune systems, as researchers led by Suphansa Sawamiphak from the Max Delbrück Center now report in the journal “Developmental Cell.”

Each year, more than 300,000 people in Germany have a myocardial infarction – the technical term for heart attack. The number of people surviving a heart attack has increased significantly, but this severe cardiac event causes irreparable damage to their hearts. A heart attack occurs when blood vessels that supply blood and oxygen to the heart muscle become blocked, causing part of the heart muscle tissue to die. This damage is permanent because the human heart has no ability to grow new heart muscle cells. Instead, connective tissue cells known as fibroblasts migrate into the damaged area of the heart muscle. They form scar tissue that weakens the pumping power of the heart. Previous attempts to use stem cells to treat infarction-damaged hearts have not been very successful.

The team led by Dr. Suphansa Sawamiphak, head of the Cardiovascular-Hematopoietic Interaction Lab at the Max Delbrück Center, is looking at the process from a different angle. “We know that both signals from the autonomic nervous system and the immune system play a pivotal role in scarring and regeneration,” says Sawamiphak. “So it stands to reason that the communication between the autonomic nervous and immune systems determines whether heart muscle scarring will occur or whether the heart muscle can recover.” It is also known that macrophages play a role in both processes. But how is this decision made?

To address this question, the researchers are studying zebrafish larvae. The fish can be easily modified and are also optically transparent, making internal processes easy to observe in the living organism. “Plus, they can fully regenerate their heart after an injury,” says Onur Apaydin, first author of the study published in “Developmental Cell.”

Signaling for regeneration

The researchers used zebrafish larvae whose heart muscle cells produce a fluorescent substance, making it easy to detect them under a microscope. They then induced an injury similar to a myocardial infarction in the larval hearts and blocked several receptors on the surface of the macrophages. The result was that adrenergic signals from the autonomic nervous system determined whether the macrophages multiplied and migrated into the damaged site. These signals also played an important role in regenerating heart muscle tissue.

In the next step, the researchers engineered genetically modified zebrafish in which the adrenergic signal reached the macrophages but could not be transmitted from the receptor into the cell’s interior. “This showed that signal transmission is crucial for heart regeneration,” says Apaydin. If signaling is interrupted, the scarring process is triggered instead.

“Our findings indicate that this is a key regulator of crosstalk between the nervous and immune systems,” says Apaydin. When macrophages are activated by the adrenergic signals of the autonomic nervous system, they in turn communicate with fibroblasts. Fibroblasts that promote regeneration alter the extracellular matrix at the damaged site. This ultimately creates a microenvironment conducive to the growth of blood and lymph vessels and to the development of new heart vessels. If, on the other hand, the signal is blocked, fibroblasts infiltrate the site and cause scarring – similar to what occurs in the human heart after a heart attack.

“We next want to examine in detail how signaling differs between zebrafish and humans,” says Sawamiphak. “This will help us understand why heart muscle tissue is unable to regenerate in humans.” The team also hopes to identify potential targets for influencing the interaction between the nervous and immune systems in a way that promotes the regeneration of heart muscle tissue and the maintenance of heart function in heart attack patients.

Photo:
Cryoinjured section of a zebrafish heart: Immunofluorescence staining elucidates cellular and extracellular compositions pivotal for cardiac repair. All cell nuclei are seen in blue, while the red stain delineates cardiomyocytes. The extracellular matrix, crucial for structural integrity and signaling, is highlighted in green. Cyan staining reveals neurons, underscoring the neuro-cardiac interactions during regeneration.

© Onur Apaydin, Max Delbrück Center

Source: Press Release Max Delbrück Center
Heart repair via neuroimmune crosstalk