Scientists at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), the Helmholtz-Zentrum Dresden-Rossendorf (HZDR), and the École Polytechnique Fédérale de Lausanne (EPFL) have developed new tools to get mechanistic insights into ether lipid biology. 

The research team used chemically modified ether lipids with two distinct reactive groups. Those so called bifunctional lipids allow to visualize ether lipid localization and study their interaction with proteins for the first time. 

A combination of fluorescence imaging, machine learning-assisted image analysis, and mathematical modelling revealed unique transport mechanisms of individual ether lipids.

“Using our new tools, we discovered that non-vesicular transport is the main mechanism for ether lipid transport,” explains Kristin Böhlig, who led the study. She continues, “However, some ether lipid types are transported faster than others, suggesting the presence of specific, so far undiscovered lipid transport proteins that can distinguish between ether lipid types.”

These results imply that the cellular lipid handling machinery is capable of identifying even small structural differences in ether lipids, adding to the evidence supporting the biological significance of lipid diversity.

“Our bifunctional ether lipid probes provide a flexible toolkit for studying ether lipid biology in detail. This will have significant benefits for understanding the functions of ether lipids in fundamental cell biology and their role in human diseases,” says André Nadler, who oversaw the study. “Studying ether lipids in mechanistic detail may in the future help to develop new treatments for diseases that are caused by imbalances in lipid metabolism.”

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“I knew that Heather Harrington, a director here at MPI-CBG, is building a community to connect math with biology. Since I deeply enjoy working with applications, I thought Dresden could be a good place to continue this work. And here I am, and I am excited to be here.” says Daniela Egas Santander.

Daniela did her bachelor's degrees in chemical engineering and mathematics at the Universidad San Francisco de Quito in Quito, Ecuador. She went to the University of Copenhagen afterwards for a master's and PhD in algebraic topology. She went to the École polytechnique fédérale de Lausanne (EPFL) in Switzerland for a postdoctoral fellowship in applied mathematics, focusing on applications to neuroscience at the laboratory of topology and neuroscience.  Afterwards, she continued working at the Blue Brain Project, which aimed to build biologically detailed brain simulations to deepen our understanding of brain function. As of October 1st, Daniela is a research group leader at the MPI-CBG and the CSBD.

Metabolism constantly maintains a flux of energy and matter that is vital to cells, so scientists speculated that thermodynamics imposes fundamental constraints on life's ability to sustain itself. Thermodynamics states that, first, energy can only change form, not be created or destroyed. Second, whenever energy is utilized, part of it must be wasted—degraded to a form that cannot be used anymore. This means that organisms must be careful: they need to expend energy to grow, but if they waste too much, they may be left without it. However, how organisms utilize energy to grow and how growth is constrained by thermodynamics remain largely unknown.

Researchers in the group of Jonathan Rodenfels at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany, and in the group of Pablo Sartori at the Gulbenkian Institute for Molecular Medicine in Oeiras, Portugal, sought to understand how the laws of thermodynamics influence cellular growth. The team realized that a black-box type of approach might be the key to solving this problem. This approach—common in bioengineering—allows researchers to work with minimal information. It cannot describe how energy is processed inside the cell, but it enables us to calculate how much energy is wasted.

Tommaso Cossetto, the lead author of the study and a former postdoctoral researcher in the Rodenfels and Sartori groups, explains, “We applied this method to a large set of data from many different published studies and used it to quantify how much energy is dissipated or wasted by microbes as they grow. We then used nonequilibrium thermodynamics—a theory from physics—to analyze this data.”

Their study, published in Nature Communications, identifies two thermodynamic rules governing the growth and energy utilization of single-celled organisms, including archaea, bacteria, and yeast. Different types of microorganisms waste about the same amount of energy to grow a unit of biomass. This is the case whether they use oxygen, inorganic molecules, or fermentation as a metabolic strategy to grow. As a second rule, however, the team found that the use of oxygen requires more energy to produce biomass. This makes aerobic respiration, the process by which a cell uses oxygen to grow, a more efficient way for cells to grow than anaerobic respiration or fermentation, as the energy wasted is a smaller proportion of the energy required.

“Our two empirical rules constitute a long-sought-after connection between metabolism and thermodynamics,” say Jonathan Rodenfels and Pablo Sartori, who oversaw the study. “We found that there are fundamental limits to how cells can grow and function. Our findings are based on observations and data, but we don't yet understand the molecular and mechanistic reasons behind these limits. Further research will help us understand how cells work and how they can be improved or optimized.”

“Dresden has a very tight connection of experiments and theory, which made it a really attractive place for me,” says Fridtjof. “The Max Planck Society is a wonderful place to focus on science, and I think it's a real privilege to have that freedom. There are many research groups here that I would love to collaborate with in the future, and I'm really looking forward to exploring new research directions here.”

Fridtjof Brauns studied physics and theoretical and mathematical physics at the Ludwig Maximilian University (LMU) in Munich. He also pursued his PhD at the LMU and went from there to the Kavli Institute for Theoretical Physics at the University of California-Santa Barbara for a postdoc with Boris Shraiman and Cristina Marchetti, where he focused on questions in development, cell- and tissue mechanics as well as active matter.

Proteins are the central molecules of life. Although the human genome codes for approx. 20,000 different proteins, there are countless variants of them. How this diversity comes about, how proteins take on their specific functions in the body – and what happens when errors occur during protein production – is investigated by Agnes Toth-Petroczy, using a novel interdisciplinary approach.

A particular focus of her research is on intrinsically disordered proteins, proteins that lack a fixed structure and therefore are difficult to analyze in conventional biochemistry. They account for up to 30 percent of the human proteome, and their function has been little understood. Moreover, she studies phenotypic mutations – errors during protein production in the cell (transcription and translation errors), which are not part of the genome. This is a broad field that has been little researched so far, but is of great importance for understanding the evolution of proteins and their role in various disease patterns.

Her current projects also analyze the collective organization of proteins into biomolecular condensates, little droplets within the cell where proteins interact with other proteins. Her research shows how such “meeting points” emerge, how they have changed in the process of evolution, and what role erroneous proteins could play in this process.

By developing innovative computer-based models and tools, she enables systems-biological investigations into previously difficult-to-access phenomena, with applications for both academic basic research to understand protein evolution and clinical applications.

“Agnes Toth-Petroczy is an exceptionally creative scientist who breaks new ground by using in-depth and innovative methodologies to reveal previously hidden dimensions of life at the molecular level,” said Max Löhning, Chairman of the Foundation Council of the Schering Stiftung, in recognition of the prize winner’s achievement.

By launching the Schering Young Investigator Award, the Schering Stiftung upgrades its tradition of promoting young talents for the 21st century. The award succeeds the Friedmund Neumann Prize and acknowledges the global nature of science. The 10,000-euro Young Investigator Award will be awarded on November 24, 2025, during a festive award ceremony at the Berlin-Brandenburg Academy of Sciences and Humanities.

About the Award Winner

Agnes Toth-Petroczy studied chemistry at Eötvös Loránd University in Budapest, Hungary, specializing in theory and computation and developing a special interest in intrinsically disordered proteins. She completed her PhD in life sciences in the lab of Prof. Dan Tawfik at the Weizmann Institute in Israel, where she studied the principles of protein evolution. As recipient of an EMBO postdoctoral research fellowship, she joined the lab of Debora Marks at Harvard Medical School (USA) where she developed computer-based methods to predict the structures of disordered proteins. She subsequently switched to translational research and worked as instructor in medicine at the Division of Genetics of the Brigham and Women’s Hospital in Boston, contributing to several novel gene-disease relationships. Since 2018, she has headed the “Protein plasticity and evolution” research group at the MPI-CBG and the CSBD. She is a member of the DFG-funded “Physics of Life” Cluster of Excellence at TU Dresden, an EMBO Young Investigator, and a recipient of an ERC Starting Grant.

Press Release of the Schering Stiftung

Lin, currently working on developing mathematical and machine-learning methods to understand complex biological datasets, came across the program through social media and was immediately intrigued. Particularly interested in the works of local mathematicians Heather Harrington and Ivo Sbalzarini, Lin has also had fruitful discussions with Anne Grapin-Botton and Michael Weber. Thomas had already visited the MPIPKS for the Fluid Physics of Life workshop in 2019 and realized the immense potential of the Dresden scientific community. He is currently developing theoretical models to determine how cellular geometry and intracellular transport are controlled and has had inspiring discussions with Pierre Haas, Christina Kurtzhaler, Heather Harrington, and Stephan Grill.

While both agree that the three months of this program may be quite short, Lin and Thomas are looking forward to building productive collaborations. “I think it is a good opportunity to extend my research field, especially since there is a great biology program here,” says Lin. Thomas adds, “I would encourage anyone with a biological problem involving geometry or mechanics to come and talk to me.”

The ELBE Visiting Faculty Program provides funded opportunities for researchers at different career stages. Visiting scientists closely interact with the CSBD and both Max Planck Institutes (MPI-CBG and MPIPKS). Through this program, the CSBD promotes networking between scientists and thereby fosters the community’s sharing of its research mission.

Anthony Hyman, a director at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany, is one of the 2025 Laureates in the field of chemistry, together with Clifford Brangwynne, director at the Omenn-Darling Bioengineering Institute and professor of Chemical and Biological Engineering at Princeton University and the Howard Hughes Medical Institute, and Michael Rosen, chair of the Biophysics Department and a Howard Hughes Medical Institute investigator at the University of Texas Southwestern Medical Center, Dallas, Texas, USA. They are selected as Citation Laureates 2025 for their discoveries on the role of phase-separated biomolecular condensates in biochemical organization of the cell.

Since 2002, ISI analysts have used publication and citation data from the Web of Science Core Collection to identify potential Nobel Prize recipients. Out of 64 million articles and proceedings indexed since 1970, less than 0.02% have been cited more than 2,000 times. Citation Laureates are selected from this elite group through rigorous citation analysis and expert insight. Since the program’s inception, 83 Citation Laureates have gone on to receive Nobel Prizes, often years after their initial recognition by Clarivate.

Citation Laureates’ foundational research papers rank among the most highly cited in their fields, reflecting exceptional influence across disciplines and borders. This year’s Laureates have advanced knowledge in fields of urgent global relevance, including:

• Physiology or Medicine: Leukemia, appetite regulation, and immune system research
• Physics: Signal processing, quantum computing, interstellar chemistry, and image compression
• Chemistry: Energy storage, green chemistry, sustainable energy, and cell engineering
• Economics: Remote work, automation, inequality, poverty, and the economic impact of culture and discrimination

Congratulations to all 2025 Citation Laureates!

Press Release from Clarivate: https://clarivate.com/news/clarivate-unveils-citation-laureates-2025/

Light sheet microscopy opens new avenues to study biological processes with unprecedented imaging speed or full coverage of entire organs and organisms. However, researchers require advanced training to meet the technological and computational challenges of light sheet microscopy. The highly interdisciplinary course covered diverse aspects of light sheet microscopy, including sample preparation, microscope assembly, physics of the light sheet, long-term live imaging, image processing, high-performance computing, and IT challenges of big image data.

Commercial as well as homemade setups were made available for the students to get familiar with the various flavors of light sheet technology. The highlight of this year’s light sheet hardware line-up was the Flamingo Light Sheet system developed by a former MPI-CBG group leader, Jan Huisken.

From model species like zebrafish to Arabidopsis plants, the students unleashed the available light sheet systems on a wide range of samples. Throughout the course, all samples were imaged using light sheet technology, producing more than 80 terabytes of raw image data. Processing, visualizing, and analyzing this data was a large part of the course and often lasted until the early morning hours.

Shiheng Zhao and Pierre Haas from the Max Planck Institute for the Physics of Complex Systems (MPIPKS) and the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), together with their experimental collaborators at Princeton University, USA, and the Flatiron Institute in New York, USA, have now developed a minimal mechanical model that explains the development of the hindgut of the fruit fly Drosophila melanogaster as an example of this passive morphogenesis.

Through their combined experimental and theoretical approaches, they found that the complex shape changes of the hindgut primordium—a group of cells that gives rise to the hindgut of the fly—can arise from mechanical forces applied by the surrounding tissues.

Daniel Alber from Princeton University and one of the lead authors of the study says, “The tissue is deformed by the surrounding tissues through a process called ‘mechanical coupling,’ whereby the mechanical forces applied by the surrounding tissues are transmitted to the hindgut primordium, causing it to change shape. Our findings suggest that  its complex shape can be explained by simple mechanical principles, rather than complex genetic mechanisms.”

Shiheng Zhao, the other lead author, adds, “Pierre Haas and I created the minimal model that could calculate the mechanical forces and hence reproduce the deformation of the tissue not only in normal fly embryos, but also in different genetic perturbations.”

Pierre Haas and Stas Shvartsman summarize, “Our study has significant implications for understanding tissue morphogenesis and the development of organs and tissues in different organisms, by highlighting the role of inter-tissue mechanical couplings for the emergence of shape in development.  Future studies will aim to uncover the molecular and cellular mechanisms that control this passive morphogenesis and its implications for tissue development and disease.”

Prof. Dr. Kai Simons (born 1938) has made groundbreaking contributions to biochemistry and cell biology, with a focus on the structure and function of cell membranes. His work has revolutionized our understanding of viral mechanisms, membrane organization, and lipid metabolism. Simons is a Finnish physician and biochemist. He began his career in Helsinki, where he used the Semliki Forest virus (SFV) as a model for studying cell membranes. This virus, with its simple lipid bilayer and single spike protein, enabled him to elucidate how detergents make membranes soluble—a breakthrough that supported the development of efficient protein subunit vaccines. His team was the first to demonstrate how SFV enters host cells, a mechanism that remains relevant for understanding enveloped viruses such as coronaviruses.

At the European Molecular Biology Laboratory (EMBL) in Heidelberg (1975–2000), Simons shifted his focus to cell surface polarity and lipid sorting in epithelial cells, which led to the discovery of the concept of lipid rafts. Lipid rafts, dynamic microdomains, organize the bioactivity of the membrane and play a crucial role in signal transduction and disease processes. In 1998, he also became founding director of the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden. He became emeritus in 2006. Simons also pioneered the field of lipidomics by using advanced mass spectrometry techniques to study lipid diversity and function. His work identified lipid biomarkers for metabolic disorders, cardiovascular disease, and diabetes, thereby supporting early detection and personalized interventions. These applications have filled an important gap in healthcare by providing tools for targeted therapies.

Simons is a member of numerous professional societies and academies such as EMBO, the National Academy of Sciences (USA), and Academia Europaea. In 1999, he was elected to the Leopoldina. He has also been honored with numerous awards and medals, including the Leopoldina's Schleiden Medal in 2001 and the Robert Koch Foundation's Robert Koch Medal in Gold in 2016.

The Cothenius Medal dates back to a foundation established by Leopoldina member and personal physician to Prussian King Frederick II, Christian Andreas von Cothenius (1708–1789). It was awarded for the first time in 1792. Initially, the award winners were honored for their work on medical research issues. Since 1954, the Leopoldina has awarded the Cothenius Medals for outstanding scientific lifetime achievement. As a rule, the awards are presented to members of the academy. Recipients include the physician and zoologist Ernst Haeckel (1864) and Konrad Zuse (1985), the developer of the first computer.

About the German National Academy of Sciences Leopoldina 

As the national academy of sciences, the Leopoldina provides independent, science-based policy advice on socially relevant issues. For this purpose, the academy develops interdisciplinary statements based on scientific findings. These publications outline options for action, leaving the decision-making to democratically legitimized politicians. The experts who draft the statements work on a voluntary basis and are open to any outcome. The Leopoldina represents German science in international committees, including providing science-based advice to the annual G7 and G20 summits. It has around 1,700 members from more than 30 countries and brings together expertise from almost all areas of research. It was founded in 1652 and designated the National Academy of Sciences of Germany in 2008. As an independent science academy, the Leopoldina is committed to the common good.

Press Release of the Leopoldina:
https://www.leopoldina.org/presse-1/pressemitteilungen/pressemitteilung/press/3160/

Small fold – big role: A tissue fold known as the cephalic furrow, an evolutionary novelty that forms between the head and the trunk of fly embryos, plays a mechanical role in stabilizing embryonic tissues during the development of the fruit fly Drosophila melanogaster.

Combining theory and experiment: Researchers integrated computer simulations with their experiments and showed that the timing and position of cephalic furrow formation are crucial for its function, preventing mechanical instabilities in the embryonic tissues.

Evolutionary response to mechanical stress: The increased mechanical instability caused by embryonic tissue movements may have contributed to the origin and evolution of the cephalic furrow genetic program. This shows that mechanical forces can shape the evolution of new developmental features.

Mechanical forces shape tissues and organs during the development of an embryo through a process called morphogenesis. These forces cause tissues to push and pull on each other, providing essential information to cells and determining the shape of organs. Despite the importance of these forces, their role in the evolution of development is still not well understood.

Animal embryos undergo tissue flows and folding processes, involving mechanical forces, that transform a single-layered blastula (a hollow sphere of cells) into a complex multi-layered structure known as the gastrula. During early gastrulation, some flies of the order Diptera form a tissue fold at the head-trunk boundary called the cephalic furrow. This fold is a specific feature of a subgroup of Diptera and is therefore an evolutionary novelty of flies.

The research groups of Pavel Tomancak and Carl Modes, both group leaders at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, looked into the function of the cephalic furrow during the development of the fruit fly Drosophila melanogaster and the potential connection with its evolution. The results of their investigation are published in the journal Nature.

A genetically patterned fold with unknown function

The researchers knew that several genes are involved in the formation of the cephalic furrow. The cephalic furrow is especially interesting because it is a prominent embryonic invagination whose formation is controlled by genes, but that has no obvious function during development. The fold does not give rise to specific structures and, later in development, it simply unfolds, leaving no trace. Bruno C. Vellutini, a postdoctoral researcher in the group of Pavel Tomancak, who led the study together with Tomancak, explains, “Our original question was to uncover the genes involved in cephalic furrow formation and the developmental role of the invagination. Later on, we broadened our investigations to other fly species and found that changes in the expression of the gene buttonhead are associated with the evolution of the cephalic furrow.”

Gene expression in the cephalic furrow of a Drosophila melanogaster embryo. Nuclei are shown in gray, and the colors represent where the genes slp1 (cyan), btd (magenta), and eve (yellow) are expressed. © Bruno C. Vellutini / MPI-CBG / Nature (2025)

With their experiments, the researchers show that the absence of the cephalic furrow leads to an increase in the mechanical instability of embryonic tissues and that the primary sources of mechanical stress are cell divisions and tissue movements typical of gastrulation. They demonstrate that the formation of the cephalic furrow absorbs these compressive stresses. Without a cephalic furrow, these stresses build up, and outward forces caused by cell divisions in the single-layered blastula cause mechanical instability and tissue buckling. This intriguing physical role gave the researchers the idea that the cephalic furrow may have evolved in response to the mechanical challenges of dipteran gastrulation, with mechanical instability acting as a potential selective pressure.

Physical model of folding dynamics

To determine the contribution of individual sources of mechanical stress, the experimentalists in the Tomancak group teamed up with the group of Carl Modes to create a theoretical physical model that behaves like the fly embryos. Carl Modes says, “Our model can simulate the behavior of embryonic tissues in fly embryos with very few free parameters. The model was fed with the data from the experiments. First, we wanted to see how the strength of the fold affects the function of the cephalic furrow. We assumed that a strong pull inside the fold is a good buffer to counteract mechanical forces. However, we discovered that the position and timing are what really matter. The earlier the cephalic furrow forms, the better of a buffer it is, and when it forms around the middle of the embryo, it proved to have the strongest buffering effect.” This physical model provides a theoretical basis that the cephalic furrow can absorb compressive stresses and prevent mechanical instabilities in embryonic tissues during gastrulation.

A related study reveals two cellular mechanisms to prevent stress

Another study, also focusing on mechanisms of how flies counteract mechanical stresses, is published at the same time in the journal Nature. The team led by Steffen Lemke from the University of Hohenheim, Germany, and Yu-Chiun Wang from the RIKEN Center for Biosystems Dynamics Research in Kobe, Japan, found two different ways how flies deal with compressive stress during embryonic development. Flies either feature a cephalic furrow or, if they lack one, display widespread out-of-plane division, meaning the cells divide downwards to reduce the surface area. Both mechanisms act as mechanical sinks to prevent tissue collision and distortion. The authors of the study worked together with the MPI-CBG researchers during the course of their studies.

Evolution of a small fold

Pavel Tomancak summarizes the results, “Our findings uncover empirical evidence for how mechanical forces can influence the evolution of innovations in early development. The cephalic furrow may have evolved through the genetic changes in response to the mechanical challenges of the dipteran gastrulation. We show that mechanical forces are not just important for the development of the embryo but also for the evolution of its development.”

Our cells are bustling with tens of thousands of types of molecules at any given time. Within this complex environment, proteins often come together with RNA or DNA and, through a process called phase separation, form ‘droplets’ known as biomolecular condensates. Numerous cellular processes are governed by condensates, yet understanding their makeup is still an active area of research. “When you want to build something, it’s not just a question of which ingredients to use, but also of how much. The ratios are essential,” says Patrick McCall, an independent research associate at the Leibniz Institute of Polymer Research Dresden (IPF) and the lead author of the study. “With condensates, the very same principle applies. We often know which components are present, but not the specific proportions inside a condensate that ultimately define its composition”. The mix of components inside a condensate are key in determining how it behaves and what it does. An analogy can be made to baking; both cake and cookies can be made with similar ingredients, but the specific ratios in the mixture are key in determining which comes out of the oven.

But how can these ratios be studied? Scientists have traditionally ‘tagged’ the individual components of a condensate, using fluorescent labels to measure their concentration. However, recent research has revealed that tagging and quantification can introduce significant errors. Commonly used tags are large enough to substantially alter the target molecule’s properties, behaviour, and even its tendency to phase separate. To complicate things further, their apparent brightness in the condensate can be unreliable. While existing “label-free” methods avoid the problems with fluorescent tags entirely, they typically struggle to distinguish between different components in a condensate. As a result, reliable measurements have been limited to simplified condensates reconstituted in a test tube from only one or two components. To understand the complex makeup of more realistic condensates, a new label-free approach to measure the components was needed. Recognising this gap, McCall initially began exploring new ways to measure condensate composition during his postdoctoral work, carried out jointly in the labs of Jan Brugués (now at the Cluster of Excellence Physics of Life) and Anthony Hyman at the MPI-CBG. Building on this lengthy collaboration with colleagues at both PoL and MPI-CBG, seminal findings have now been published in Nature Chemistry, highlighting a novel, label-free method to measure the composition of multi-component condensates. This is an essential step towards understanding the physical properties and function of these droplets.

Their new method, Analysis of Tie-lines and Refractive Index (ATRI), combines two physical concepts – the refractive index and tie-line – to determine the composition of a condensate. The refractive index of a medium describes how much light bends when passing through it. Using quantitative phase imaging (QPI), a powerful label-free microscopy tool, the authors could measure the refractive index difference between micron-sized condensates and the surrounding medium, the “dilute phase”, to determine the concentration. When a condensate is made of just a single protein, the QPI measurement immediately provides an estimate of concentration inside the condensate. However, certainty turns to ambiguity when more than one component is present, as different combinations of molecules can produce the same refractive index. This makes it difficult to determine the exact ratios of each component inside multi-component condensates. To resolve this confusion, ATRI uses a tie-line. The tie-line is a fundamental concept in physical chemistry that relates the compositions of two phases following phase separation – the condensate and the surrounding dilute phase – to the composition of the overall system. The key realization behind ATRI is that combining refractive index measurements with the tie-line graphically results in two lines that meet at one specific point: the point representing condensate composition. Using the refractive index and tie-line as inputs, ATRI generates a set of equations to pinpoint the concentration of multiple different components in a condensate, thereby determining its composition. This technique can be applied even in mixtures with many different molecules, and even when only tiny quantities are available.

Utilising their new approach, the authors successfully revealed the composition of complex condensates in unprecedented detail, resolving the concentrations of five molecules. At the time of publication, experiments capable of resolving more than two proteins in a condensate without using fluorescence have not been reported previously, highlighting the significance of this new method. By revealing the composition of condensates quantitatively, their behaviour and properties may be predicted with greater accuracy than ever before, paving the way for new insights. In addition, researchers can now use ATRI to study how condensates react to variation in the abundance of a particular component, mimicking changes in gene expression that normally happen in a cellular environment. Such experiments will help uncover the contribution of individual components to overall condensate behaviour and function. Beyond basic science, the new method has the potential to drive biomedical advances as well. Condensates play a role in numerous disorders and, by exposing how a condensate’s molecular makeup responds to promising compounds, ATRI may aid the development of potent therapeutics and treatments in future.

Funding: This study was supported by Volkswagen ‘Life’ grant number 96827 and the Deutsche Forschungsgemeinschaft (DFG) under Germany's Excellence Strategy, Cluster of Excellence Physics of Life of TU Dresden (EXC-2068–390729961). Researchers were additionally supported by an ELBE Postdoctoral Fellowship from the Center for Systems Biology Dresden and the Biocondensate Emerging Topic at the IPF.

New technique to image single lipids: Lipids are notoriously difficult to detect with light microscopy. Using a new chemical labeling strategy, the Dresden team has overcome this limitation, enabling novel insights into where specific lipids are located and how they are transported in cells.

Map of lipid flow: The researchers used the new lipid imaging method to answer the long-standing question how cells transport specific lipids to their target organelle membranes. The study revealed that non-vesicular lipid transport by proteins is the primary mechanism that maintains the membrane composition of specific organelles.

Understanding the role of lipids in diseases: Lipid imbalances play a role in several metabolic or neurodegenerative diseases. The new lipid-imaging technique will help understand the role of lipid transport in health and disease. The identification of the proteins involved in selective lipid transport can accelerate further discoveries of new drug targets for lipid-associated diseases.

Lipid molecules, or fats, are crucial to all forms of life. Cells need lipids to build membranes, separate and organize biochemical reactions, store energy, and transmit information. Every cell can create thousands of different lipids, and when they are out of balance, metabolic and neurodegenerative diseases can arise. It is still not well understood how cells sort different types of lipids between cell organelles to maintain the composition of each membrane. A major reason is that lipids are difficult to study, since microscopy techniques to precisely trace their location inside cells have so far been missing.

In a long-standing collaboration André Nadler, a chemical biologist at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany teamed up with Alf Honigmann, a bioimaging specialist at Biotechnology Center (BIOTEC) at the TUD Dresden University of Technology, to develop a method that enables visualizing lipids in cells using standard fluorescence microscopy. After the first successful proof of concept, the duo brought mass-spectrometry expert Andrej Shevchenko (MPI-CBG), Björn Drobot at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR), and the group of Martin Hof from the  J. Heyrovsky Institute of Physical Chemistry in Prague on board to study how lipids are transported between cellular organelles.

Artificial lipids under the sunbed

“We started our project with synthesizing a set of minimally modified lipids that represent the main lipids present in organelle membranes. These modified lipids are essentially the same as their native counterparts, with just a few different atoms that allowed us to track them under the microscope,” explains Kristin Böhlig, a PhD student in the Nadler group and chemist who was in charge of creating the modified lipids.

The modified lipids mimic natural lipids and are “bifunctional,” which means they can be activated by UV light, causing the lipid to bind or crosslink with nearby proteins. The modified lipids were loaded in the membrane of living cells and, over time, transported into the membranes of organelles. The researchers worked with human cells in cell culture, such as bone or intestinal cells, as they are ideal for imaging.

“After the treatment with UV light, we were able to monitor the lipids with fluorescence microscopy and capture their location over time. This gave us a comprehensive picture of lipid exchange between cell membrane and organelle membranes,” concludes Kristin.

In order to understand the microscopy data, the team needed a custom image analysis pipeline. “To address our specific needs, I developed an image analysis pipeline with automated image segmentation assisted by artificial intelligence to quantify the lipid flow through the cellular organelle system,” says Juan Iglesias-Artola, who did the image analysis.

Speedy lipid transport by proteins

By combining the image analysis with mathematical modeling, done by Björn Drobot at the HZDR, the research team discovered that between 85% and 95% of the lipid transport between the membranes of cell organelles is organized by carrier proteins that move the lipids, rather than by vesicles. This non-vesicular transport is much more specific with regard to individual lipid species and their sorting to the different organelles in the cell. The researchers also found that the lipid transport by proteins is ten times faster than by vesicles. These results imply that the lipid compositions of organelle membranes are primarily maintained through fast, species-specific, non-vesicular lipid transport.

In a parallel set of experiments, the group of Andrej Shevchenko at the MPI-CBG used ultra-high-resolution mass spectrometry to see how the different lipids change their structure during the transport from the cell membrane to the organelle membrane.

A boost for lipids in cell biology and disease

This new approach provides the first-ever quantitative map of how lipids move through the cell to different organelles. The results suggest that non-vesicular lipid transport has a key role in the maintenance of each organelle membrane composition.

Alf Honigmann, research group leader at the BIOTEC says, “Our lipid-imaging technique enables the mechanistic analysis of lipid transport and function directly in cells, which has been impossible before. We think that our work opens the door to a new era of studying the role of lipids within the cell.”

Imaging of lipids will allow further discoveries and help to reveal the underlying mechanisms in diseases caused by lipid imbalances. The new technique could potentially help to develop new druggable targets and therapeutic approaches for lipid-associated diseases, such as nonalcoholic fatty liver disease.

“We knew that we were onto something big”

André Nadler, research group leader at MPI-CBG, looks back at the start of the study, “Imaging lipids in cells has always been one of the most challenging aspects of microscopy. Our project was no different. Alf Honigmann and I started discussing about solving the lipid imaging problem as soon as we got hired in close succession at MPI-CBG in 2014/15 and we quickly decided to go for it. It still took us almost five years from the start of the project to the point in autumn 2019 when the two of us finally produced a sample with a beautiful plasma membrane stain. That’s when we knew that we were onto something big. As a reward, certain well known global events meant we were required to shut down our laboratories a few months later. In the end, the delay was for the best. Before the revolution in the use of artificial intelligence in image segmentation, we would not have been able to properly quantify the imaging data, so our conclusions would have been much more limited.”

Researchers still need to determine which lipid-transfer proteins drive the selective transport of different lipid species. They also need to identify the energy sources that power lipid transport and ensure that each organelle keeps its own unique membrane composition.

The research group of Pavel Tomancak at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), in collaboration with the groups of Carl Modes (MPI-CBG) and Christoph Zechner (MPI-CBG Alumni), took a closer look at this question. To study the self-organization abilities of cells without external environmental interference during the patterning process, the researchers worked with Hydra, a small freshwater invertebrate animal belonging to the phylum Cnidaria, which is known for its simple body plan and its regenerative capabilities.

“We mixed up 10,000 to 100,000 cells of Hydra into a clump of dissociated cells. Through the amazing regenerative abilities, the cell clump was able to form tissues and create a new pattern and shape and even a complete Hydra,” explains Anaïs Bailles, the leading author of the study together with Pavel Tomancak. “To understand the mechanisms behind this, we perturbed the tissue’s physical constraints. While a change in topology and geometry did not have a direct effect, a stretch on one side strongly biased the orientation of actin, a meshwork of hair-like filament structures that give the cell its mechanical properties. In the direction of where we stretched, the body axis of the Hydra aligned, and later the head appeared.”

Pavel Tomancak summarizes, “We show that tissue mechanics can trigger the mechanochemical self-organization toward a functional organism. These results provide new insights into the mechanisms of organism shape formation and have implications for our understanding of development and tissue engineering.”

HFSP Long-Term Fellowships are awarded to postdocs with a Ph.D. in Biology who want to embark on a novel and frontier project in the life sciences. Together with the HFSP Cross-Disciplinary Fellowships, they foster the next generation of life science research, last for three years, and on average provide $200,000 USD in total. Fellows work in a host laboratory located in a different country from where their Ph.D. was conferred.

Augusto received his doctoral degree in biology from the Graduate School of the Stowers Institute for Medical Research in Kansas City, USA. His funded project in Germany focuses on identifying the proteins responsible for generating, transducing, and changing osmotic pressure. He will use a new osmotic sensor developed in the Campàs group to directly measure osmolarity in pancreatic organoids and living tissues.

“In my project, we will investigate the interplay between physics and biology. We understand that biological systems are constrained by physics, and we believe that the evolution of proteins and their regulation led to clever leverage of these physical constraints,” explains Augusto. “We will focus on pancreas development in the mouse, where hollow lumens emerge in ten-day-old embryos and grow to become a complex tree-like structure that carries pancreatic enzymes into the gut. We want to understand how osmotic regulation contribute to this process, and more generally identify physical mechanisms deployed during embryonic development.”

The project will use a challenging but innovative approach of directly measuring physical parameters. It will pair experiments with theoretical analyses to build a model that accounts for dynamic osmotic pressure and cellular feedback mechanisms that shape the organ during development. The goal of the project is to advance the fundamental understanding of embryology and tissue dynamics, and serve as the seed for therapeutic interventions for people who suffer from cystic fibrosis. These patients display increased osmotic pressure in lumen mucus secretions, and there is a need to understand the pathophysiological consequences of changes to osmolarity in the lumen.

HFSP news article: https://www.hfsp.org/hfsp-news/hfspawardees2025

A recent study, led by Theresia Gutmann in the research lab of Anthony Hyman at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany, published in PNAS, uncovers a novel mechanism that may explain why cGAS stays inactive at the onset of the disease.

To understand how SARS-CoV-2 might interfere with the immune system, the researchers focused on one of the virus’s key structural components: the nucleocapsid protein, which is produced in large quantities in the infected cell. Its primary function is to package the viral RNA genome (a molecule that carries the virus’s genetic code, similar to DNA) so that it can fit into the tiny virus particles. The team investigated the interplay between the SARS-CoV-2 nucleocapsid protein and the DNA immune sensor cGAS. Biochemical and biophysical experiments revealed that the nucleocapsid protein binds not only to RNA but also to DNA. “This strong binding to DNA was unexpected, as the nucleocapsid protein is a specialized RNA-binding protein that evolved to bind the viral RNA genome. Viral RNA is structurally very different from our DNA,” says David Kuster, joint first author of the study. The viral nucleocapsid protein masks the DNA from cGAS detection, preventing an immune response.  

This discovery adds a fresh twist to the repertoire of coronaviral immune evasion tricks. Future research will show whether this trick may be a common tactic used by other viruses to evade the immune system.

Researchers at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), the Max Planck Institute for the Physics of Complex Systems (MPIPKS), and the Center for Systems Biology Dresden (CSBD) have developed a new approach to address these questions, based on an exhaustive analysis of all small interaction networks (of up to five species). Yu Meng, Szabolcs Horvát, Carl Modes, and Pierre Haas analyzed hundreds of thousands of networks numerically and established a mathematical theorem relating the possibility of stability of coexistence in a community to its subcommunities. The authors discovered that even small changes to the network of ecological interactions hugely affect the possibility of stable coexistence.

“We also found that a very small fraction of networks are what we named ‘impossible ecologies’, in which coexistence is simply not possible,” says Carl Modes.

“Our study highlights that it is really the full structure of the network of interactions that determines the stability of ecosystems. Our results can therefore help us to better understand how ecosystems will respond to environmental changes,” summarizes Pierre Haas.

The authors are now collaborating with the mathematics research groups at the MPI-CBG and the CSBD to extend their numerical approaches and results to larger ecological communities using new mathematical tools.

The new research training group will focus on so-called biomolecular condensates – membrane-less structures within living cells that play a central role in the spatial and temporal organization of biological processes. This emerging field of research holds great promise for uncovering fundamental principles of life. In particular, the GRK 3120 aims to investigate how phase transitions and collective interactions among biopolymers contribute to the formation and function of biomolecular condensates. In the long term, these insights may also inspire advances in medicine — for example, by deepening our understanding of neurodegenerative diseases.

RTG 3120 will integrate a broad spectrum of experimental and theoretical approaches across the Dresden research landscape to understand, predict, and precisely control the physics and biological functions of condensates. Furthermore, their specific role in diseases will be investigated, and their potential for innovative therapeutic strategies explored. To achieve these goals, the research group brings together a consortium of outstanding partners: In addition to TUD, the Leibniz Institute for Polymer Research (IPF), the Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG), and the Helmholtz Center Dresden-Rossendorf (HZDR) are also involved.

A central question is: How do proteins and other biological macromolecules cooperate to carry out biological functions at the right time and in the right place? RTG 3120 supports doctoral researchers who are passionate about interdisciplinary science at the interface of biology, physics, and polymer research, and who are eager to push the boundaries of knowledge with curiosity and creativity. Dresden offers a uniquely fertile environment for this endeavor, since it was here that research on biomolecular condensates first emerged: Anthony Hyman (MPI-CBG), Clifford Brangwynne (Princeton University and Howard Hughes Medical Institute), and Frank Jülicher (MPI for the Physics of Complex Systems) discovered the completely new physical principle of biomolecular condensates, which condense cellular interactions between proteins and other biomolecules without the presence of membranes. As a result, Dresden developed a vibrant scientific network spanning cell biology, biochemistry, polymer science, and physics.

RTG spokesperson Jens-Uwe Sommer, Professor of Polymer Theory at TUD and Division Director at the Leibniz Institute for Polymer Research Dresden, explains: "By investigating collective phenomena at the interface of biology, biological physics and polymer physics, we aim to contribute to a new foundation for understanding living matter—and at the same time create an inspiring interdisciplinary environment for the next generation of excellent researchers."

Press release from the TU Dresden