With their collaborative project, Nadler, Huch and Honigmann are aiming to apply a technology they developed to visualize fats in cells using a fluorescence microscopy. Our bodies are built on fats and their molecular cousins, collectively known as lipids. These slippery molecules construct our cell walls and store 90% of our energy, and their dysregulation is associated with diseases like diabetes and fatty liver disease. Lipids cannot easily be visualized in cells, which complicates analyses of their biological functions. The researchers address this issue head-on in their project and will use their technology to study the turnover and transport of lipids in laboratory models of the intestine and the liver, two organs essential for metabolism.

The eight awarded projects were selected from open calls for proposals in two fields: protein lifespan and nutrient sensing. To choose research areas that they recommend for funding, the Frontiers Group looks for emerging fields where an investment could be catalytic to advance scientific progress — not just for awardees, but for all in that particular field. 

Congratulations!

About The Paul G. Allen Frontiers Group 
The Paul G. Allen Frontiers Group, a division of the Allen Institute, is dedicated to exploring the landscape of bioscience to identify and foster ideas that will change the world. The Frontiers Group recommends funding through award mechanisms to accelerate our understanding of biology, including: Allen Discovery Centers at partner institutions for leadership-driven, compass-guided research; and Allen Distinguished Investigators for frontier explorations with exceptional creativity and potential impact. The Paul G. Allen Frontiers Group was founded in 2016 by the late philanthropist and visionary Paul G. Allen. For more information, visit allenfrontiersgroup.org.  

An international research team from the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), the Center for Systems Biology (CSBD), both located in Dresden, Germany, the University of Lausanne in Switzerland, the Tokyo Institute of Technology in Japan, and the Human Technopole in Milan, Italy investigated several transcription machinery components and how they come together to activate the transcription process. The researchers looked at the early development of a zebrafish embryo, because this is a fitting model to study transcription bodies. They knew already that the transcription factor Nanog is involved in the transcription process of the zebrafish. “We observed several proteins and found that Nanog was the first one that clusters, then others follow, to form transcription bodies,” explains Ksenia Kuznetsova, the first author from the research group of Nadine Vastenhouw, former research group leader at the MPI-CBG and now located at the University of Lausanne. “When we removed Nanog, we could see that the other proteins were not recruited and the transcription bodies did not form.”

This study shows for the first time a sequential recruitment of proteins that form transcription bodies, which are needed for the transcription process, and that transcription factors can organize transcription bodies. Since transcription is a fundamental process in biology, this study provides an important step towards understanding how factors that activate this process are organized so that the appropriate products are made, cells take up the right fate and collectively become the right tissue, and the organism can develop normally.

The upcoming lectures will be held from 14:30–15:30 in the MPI-CBG Auditorium in German on the dates listed below. Everybody is welcome!

10. January 2023
Kristin Böhlig
Let it glow! Wie Chemiker Fette in der Zelle zum Leuchten bringen und warum
Let it glow! How chemists can make fats in the cell glow and why

07. February 2023
Justina Stark
Auf dem Weg zum “Computer Embryo”
On the way to the “computer embryo”

The INSA in New Delhi is one of three national academies for Indian scientists in all branches of science and technology. Established in 1935, it promotes science and scientific knowledge in India for the cause of humanity and national welfare. Currently, there are a total of 968 Fellows and 96 Foreign Fellows.

Elisabeth Knust has had contacts and collaborations with Indian scientists for many years, mainly at the National Centre for Biological Sciences (NCBS) in Bangalore and the Tata Institute of Fundamental Research (TIFR) in Mumbai. These collaborations were funded by the Max Planck Society, the Max Planck-NCBS Center on Lipid Research, and the German Academic Exchange Service (DAAD). She recruited the first postdoc funded by the joint NCBS/inStem/MPI-CBG Joint Postdoctoral Program, a structured exchange program to encourage scientific collaborations between MPI-CBG and NCBS/inStem. Furthermore, Knust served in various scientific committees in India.  

When asked what this recognition meant to her, Knust said, “I have been involved with Indian research institutes since more than 25 years. The election to the Indian National Science Academy is an honor for me and I hope it will enable me to strengthen the ties between German and Indian research institutes further.”

Knust is also a member of the German National Academy of Sciences Leopoldina since 2015 and received the Gottfried Wilhelm Leibniz Prize in 1997.

Congratulations, Eli!
 

List of all newly elected Foreign Fellows 2022:
https://insaindia.res.in/fef.php
 

The collective interaction of cells leads to the shaping of an organism during development. The different organs feature various geometries and differently connected three-dimensional structures that determine the function of fluid-filled tubes and loops in organs. An example is the branched network architecture of the kidney, which supports the efficient filtration of blood. Observing embryonic development in a living system is hard, which is why there are so few concepts that describe how the networks of fluid-filled tubes and loops develop. While past studies have shown how cell mechanics induce local shape changes during the development of an organism, it is not clear how the connectivity of tissues emerges. By combining imaging and theory, the researcher Keisuke Ishihara started to work on this question first in the group of Jan Brugues at the MPI-CBG and MPI-PKS. He later continued his work in the group of Elly Tanaka at the IMP. Together with his colleague Arghyadip Mukherjee, formerly a researcher in the group of Frank Jülicher at MPI-PKS, and Jan Brugués, Keisuke used organoids derived from mouse embryonic stem cells that form a complex network of epithelia, which line organs and function as a barrier. “I still remember the exciting moment when I found that some organoids had transformed into tissues with multiple buds that looked like a bunch of grapes. Describing the change in the three-dimensional architecture during development proved to be challenging, though,” remembers Keisuke and adds, “I found that this organoid system generates astonishing internal structures with many loops or passages, resembling a toy ball with holes.”

Studying the development of tissues in organoids has several advantages: they can be observed with advanced microscopy methods, making it possible to see dynamic changes deep inside the tissue. They can be generated in large numbers and the environment can be controlled to influence development. The researchers were able to study the shape, number, and connectivity of the epithelium. They tracked the changes in the internal structure of organoids over time. Keisuke continues, “We discovered that tissue connectivity emerges from two different processes: either two separate epithelia fuse or a single epithelium self-fuses by fusing its two ends, and thereby creating a doughnut shaped loop.” The researchers suggest, based on theory of epithelial surfaces, that the inflexibility of epithelia is a key parameter that controls epithelial fusion and in turn the development of tissue connectivity.

The supervisors of the study, Jan Brugues, Frank Jülicher, and Elly Tanaka conclude, “We hope that our findings will lead to a fresh view of complex tissue architectures and the interplay between shape and network connectivity in organ development. Our experimental and analysis framework will help the organoid community to characterise and engineer self-organising tissues that mimic human organs. By revealing how cellular factors influence organ development, these results may also be useful for developmental cell biologists who are interested in organisational principles.”

A lecture on treatment options for advanced age-related macular degeneration (PD Dr. med. Boris Stanzel, Augenklinik Sulzbach and Knappschaftsklinikum Saar GmbH) opened the day, followed by a presentation of the naviBelt (feelSpace GmbH). After a coffee break,  Dr. med. Dierk Wittig from the University Hospital Dresden presented an overview of the therapy options for age-related macular degeneration and Prof. Dr. Marius Ader from the CRTD discussed his latest research on the photoreceptor replacement by cell transplantation. The highlight of the event was the official closing of the summer rowing challenge in which Ms. Anne Kinski (PRO RETINA Deutschland e.V.) collected over 12 thousand euros for Prof. Ader’s research at the CRTD. The event was finished with an open discussion forum where the speakers of the day answered questions from the audience. During the coffee and lunch break, several partners presented their work at six information booths.

These diverse contributions bridge basic research with therapeutic applications and integrate the valuable work of self-help groups. Many of the research approaches aim to facilitate therapies for the treatment of visual impairment and thus improve the quality of life of those affected. Recent years have also shown that many people with visual impairments and their relatives come to Retina Day not only to hear about the latest research but also to talk to other people affected and build a network.

At birth, a baby starts to eat food and turns it into energy. Many nutrients can be converted to sugar (glucose) and be released into the bloodstream. Higher blood sugar levels signal the beta cells in the pancreas to release insulin, which lets the blood sugar into the cells to use or store it as energy. However, at different stages of life, the food-sensing beta cells need to adapt to different foods and needs. In a recent study in Nature Communications, Anne Grapin-Botton, director at MPI-CBG, and her team in Dresden and at the Novo Nordisk Foundation Center for Stem Cell Biology in Copenhagen, Denmark, together with colleagues from the Faculty of Medicine Carl Gustav Carus of the Technische Universität Dresden found that the gene Wnt4 becomes active in food-sensing beta cells as they mature in early postnatal life.

How it all began
The discovery of the role of Wnt4 in the development of a pancreas started in the 1990s at Harvard University, when Anne Grapin-Botton, a postdoctoral researcher at that time, discussed with Seppo Vainio, now a research unit leader at the University of Oulu. “I remember that when I worked with Wnt4 in kidney development, we speculated that this signal would have a role in the development of the pancreas too,” says Seppo Vainio. But the researchers were lacking the right tools at that time. Over 20 years later, postdoctoral researcher Keiichi Katsumoto in the lab of Anne Grapin-Botton was keen on finding out what function the gene Wnt4 has in pancreas development. In the meantime, the lab of Vainio at Oulu had further developed their mouse models: “With all these tools, we could target Wnt4 function in pancreas development and physiology with Anne Grapin-Botton’s research lab,” says Seppo Vainio.

Exciting communication between beta cells
Keiichi Katsumoto describes what he observed, “We found that the gene Wnt4 is expressed in beta cells during the maturation of the cell. The cells that start expressing Wnt4 stop proliferating and become more functional. We saw that with less Wnt4, the beta cell secretes less insulin.” The team found that even though the beta cells were able to detect sugar in the blood, they secreted less insulin in response to glucose.

“When we saw that mice without the gene Wnt4 were becoming diabetic, we knew we had found something important, but we did not understand how it was acting,” says Anne Grapin-Botton, who supervised this study. “We understood from work in other organs, notably our collaborator Seppo Vainio and his colleagues, that this gene is a signal sent by cells to others. It was exciting to find communication between beta cells in the pancreas, its conservation across several animal species and the mechanisms by which it operates, notably the profound metabolic changes it provokes in beta cells. However, we do not understand yet if beta cells release Wnt4 constantly or under special circumstances. This will be something, we want to explore in the future.”

“The results also suggest that the increase of Wnt4 shortly after birth enables beta cells to mature," says Katsumoto. Our next step is to understand why Wnt4 becomes expressed as the cells mature.” Those results could support the development replacement beta cells for diabetes therapy with added Wnt4 to promote maturation.

Press release from the University of Oulu in Finnish

Congratulations!

Together with DNA and proteins, lipids comprise an important class of biomolecules. However, lipids composition and how it is affected by diverse pathophysiological processes remains poorly understood. The human lipidome, a full constellation of lipids in the human body, may comprise over 100,000 unique lipid species. Kai Simons and Andrej Shevchenko worked together to develop the quantitative shotgun lipidomics platform. Shotgun methodology does not use front-end separation of total lipid extracts and relies on high-resolution mass spectrometry to identify the molecular species of lipids and determine their absolute (molar) quantities. Hence, shotgun lipidomics excels and enables molecular diagnostics of a wide spectrum of metabolic disorders.

Andreas Greinacher and his research team discovered the cause of “VITT syndrome-vaccine-induced immunogenic thrombotic thrombocytopenia (VITT),” which occurs after a vaccination with adenovirus vector-based COVID-19 vaccines. The discovery of “VITT syndrome,” the development of a detection method, the clarification of the mechanism, and the identification of effective treatment drugs meant that severe complication rates could be reduced by more than 90 percent.

Professor Harald Renz, President of the German Society for Clinical Chemistry and Laboratory Medicine, said: “We are once again pleased to be able to honour three outstanding scientists this year from around the world, who absolutely fulfil the award’s demanding criteria. Their scientific contribution is setting the standard for chemical analysis and is helping to improve the healthcare of millions of people.”

About the Biochemical Analytics Prize
The Biochemical Analytics Prize has been conferred every two years since 1970 by the German Society for Clinical Chemistry and Laboratory Medicine e. V. (DGKL) for outstanding scientific achievements in the field of biochemical and molecular analytics. The award recognises methodological advances as well as important discoveries that has been gained using modern analytical methods in the field of biological sciences, especially clinical chemistry and clinical biochemistry. The award is sponsored by the globally active company SARSTEDT Group.

Six Nobel prize laureates and several scientists of Max Planck Society, such as Nobel Laureates Emmanuelle Charpentier, Svante Pääbo and Georges J.F. Köhler, as well as Franz-Ulrich Hartl, Wolfgang Baumeister and Matthias Mann, have already been honoured with this award.

The course was led by Rob Phillips, the Fred and Nancy Morris Professor of Biophysics, Biology, and Physics at the California Institute of Technology, USA. Rob’s partner was Tom Röschinger, a graduate student in his lab. DRESDEN-concept supported the course generously.

Until recently, it was thought that organelles—specialized subunits surrounded by membranes—performed the majority of the work in a cell. But Anthony Hyman and Clifford Brangwynne discovered an entirely new physical principle that concentrates cellular interactions between proteins and other biomolecules in the absence of membranes. They described dynamic liquid-like droplets that form rapidly by phase separation—similar to oil droplets forming in water —producing temporary structures protected from the molecular turmoil of the watery cell interior. Since their discovery, they and others have shown that these membraneless liquid condensates play a role in numerous cellular processes, including cellular signalling, cell division, the nested structure of nucleoli in the cell nucleus, and the regulation of DNA. Their discovery is a fundamental advance in our understanding of cellular organization and is likely to lead to clinical applications in the future, including for neurodegenerative diseases such as ALS.

“Neurodegenerative disease breakthroughs, quantum computing, AI solving protein structure, and more…” said Sergey Brin, “These are incredible advances that deserve to be celebrated.” 

“Congratulations to all of the Breakthrough Prize winners, whose incredible discoveries will pave the way for scientific discovery and spur innovation,” said CZI Co-Founders and Co-CEOs Priscilla Chan and Mark Zuckerberg. “These laureates and early-career scientists are pushing the boundaries of what’s possible in research and science, and we’re thrilled to honor their accomplishments.”

“The laureates honored today embody the remarkable power of fundamental science,” said Yuri Milner, “both to reveal deep truths about the Universe, and to improve human lives.”

 “The 2023 laureates have produced absolutely stellar science,” said Anne Wojcicki. “The creativity, ingenuity and sheer perseverance that went into this work is awe-inspiring.”

Launched in 2013 by a group of Internet and technology entrepreneurs, the Breakthrough Prize in Life Sciences recognizes “transformative advances toward understanding living systems and extending human life.” A $3-million cash award accompanies the Breakthrough Prize, making it the richest prize in the life sciences. In addition, up to three New Horizons in Physics Prizes, up to three New Horizons in Mathematics Prizes, and up to three Maryam Mirzakhani New Frontiers Prizes are given out to early-career researchers each year. The Breakthrough Prizes were founded by Sergey Brin, Priscilla Chan and Mark Zuckerberg, Yuri and Julia Milner, and Anne Wojcicki. Laureates attend a gala award ceremony designed to celebrate their achievements and inspire the next generation of scientists. The Prizes have been sponsored by the personal foundations established by Sergey Brin, Priscilla Chan and Mark Zuckerberg, Ma Huateng, Jack Ma, Yuri and Julia Milner and Anne Wojcicki.

Anthony Hyman, 60, was born in the Israeli city of Haifa. After studying zoology at University College, London, he earned his doctorate at King's College, Cambridge, in 1987 on embryonic cell divisions of the nematode Caenorhabditis elegans. As a postdoctoral fellow, he went to the University of California, San Francisco. In 1993, Hyman became a group leader at the European Molecular Biology Laboratory in Heidelberg. In 1999, he was one of the founding members of the Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, which he still heads together with a team of directors. He has been a Fellow of the British Royal Society since 2007, an international member of the American National Academy of Sciences since 2020, and a member of the German National Academy of Sciences Leopoldina since 2021. In 2022, he received the Körber Prize for European Science.

Information on the Breakthrough Prize is available at breakthroughprize.org
Press Release on the 2023 Breakthrough Prize
Press Release of the University of Princeton

Meritxell Huch, director at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, received the GSCN 2022 Hilde Mangold Award for her pioneering research on organoids from several organs including stomach, liver and pancreas, both from animal models and human tissues. Currently, Meritxell and her research group are developing human organoid models to study the molecular and cellular basis of adult human tissue regeneration. The goal is to understand in detail how human tissue regenerates and how these mechanisms are disrupted in disease. The GSCN Hilde Mangold Award recognizes Meritxell Huch for her pioneering work and sustained outstanding research at the fore front of the organoid field.

The GSCN 2022 Young Investigator Award was awarded to Simon Haas from the Berlin Institute of Health (BIH), the Charité and the Max Delbrück Center for Molecular Medicine (MDC) in Berlin and the GSCN 2022 Publication of the Year Award went to Adam C. O’Neill, Fatma Uzbas, Giulia Antognolli, Florencia Merino, and Magdalena Götz from Helmholtz Zentrum München and Ludwig-Maximilians-University Munich (LMU).

Awarded annually, the GSCN Female Scientist Award has now been rebranded as the GSCN Hilde Mangold Award. The new name is in recognition of German embryologist Hilde Mangold (1898 -1924). Mangold performed key experiments which paved the way for the discovery of the embryonic organizer, thereby playing a seminal role in the development of embryology. Her early death in a tragic accident prevented her from being honored together with Hans Spemann when the latter was awarded the Nobel Prize for the discovery of the organizer effect in 1935. The annual GSCN science prize is bestowed to outstanding female stem cell researchers. In addition to scientific achievement, the jury also aims to recognize the award winner’s lifetime achievement as a role model for young female scientists. As before, women continue to be underrepresented in stem cell research leadership positions at universities and research institutes.

The GSCN has been networking stem cell researchers working in Germany nationally and internationally since 2013 and communicates their results and research to a broad public. The promotion of young scientists and the presentation of outstanding female scientists receive special attention at the GSCN with the GSCN Hilde Mangold Award. Since 2021, the GSCN closely cooperates with the Berlin Institutes of Health (BIH) in the jointly
founded “Dialogue Platform Stem Cell Research.”

Press release of the German Stem Cell Network

GSCN Awardees 2022

At this year’s ISTT conference, the prize was awarded to Ronald on September 18th, where he gave a talk about his newly developed technique. Ronald received free 2023 membership, free registration for the TT2023 meeting, and a cash prize of 500 euros, all sponsored by Janvier Labs.

The generation of mutant mouse models for biomedical research still plays a major role in understanding processes in the organism. Mutations are still first integrated into mouse embryonic stem cells (mES-cells). A large number of matings has to be performed in order to firmly establish the mutation of a newly generated mouse line in the first generation. In this way, a large number of offspring have no scientific value. Through collaboration with Peter Dobrowolski, Ronald succeeded in developing a forensic analysis system that detects an exact guarantee of a mutation already in the sperm. Thus, it is predictable that the mutation will be passed down to the following generation. This reduces the need for a substantial number of test animals, as well as time and money.

Ronald Naumann says, “I have been working in research with laboratory animals for over 25 years. Very often we have been able to reduce animal numbers through technical or biotechnical developments in the sense of the 3Rs. The STR-IVF technique now developed will be of great benefit to many laboratories worldwide. It also shows that scientists take the 4th R, “Responsibility”, very seriously and exert positive influence on the development of better systems themselves.”

Right after an egg cell is fertilized, the formation of the cell cortex begins, and it takes about ten minutes until it is fully formed. The cortex consists of actin filaments and motor proteins, which are organized into a dense crosslinked network. The dynamics of the cortex stem from motor proteins pulling on actin filaments, generating stresses that result in cortical tension. This cortical tension drives, for example, the shape of cells, their ability to sense their environment and their ability to perform their functions in our bodies. The dynamics of the cell cortex has been intensely studied in the past, but the mechanism by which the cell cortex is first activated right after fertilization is unknown. It is crucial to understand the principles behind the cell cortex formation since it is involved in almost every function of the cell, and improper cortical organization leads to an impairment of key cellular and developmental processes.

Protein condensates have a short life and ensure proper development.
To investigate how the cell cortex gets activated, an interdisciplinary team of researchers at MPI-CBG, MPI-PKS, and PoL studied this process in the roundworm C. elegans. “We were able to observe how actin and the actin-nucleating proteins WSP-1 and ARP2/3 came together to assemble into condensates that lasted only seconds, just to disassemble right thereafter. These condensates ensure that there is the right amount of actin filaments and that they are connected in just the right way. To me, the beauty of these structures, made of highly branched actin filaments, like a snowflake, lies in what their dynamics teach us about the unconventional chemistry of living matter,” explains Arjun Narayanan, one of the lead authors of the study and researcher in the group of Stephan Grill, director at MPI-CBG. Victoria Tianjing Yan, the other lead author, continues, “We developed our own imaging and image analysis method, called mass balance imaging, to study how the structure of the short-lived condensates grows and evolves.” During their studies, the researchers found that internal chemical reactions control how fast a condensate grows and when it shrinks away. Thus, cortical condensates robustly organize their own life cycle, largely independent of their external environment.

Stephan Grill summarizes, “We conclude that the condensates in the cell cortex represent a new type of biomolecular condensate driven by specific chemical reactions to assemble and disassemble within seconds.” He adds, “We suggest that these short-lived condensates control the activation of the cell cortex and the delicate precision of its growing architecture after fertilization of the C. elegans oocyte. Frank Jülicher, director at MPI-PKS and another supervising author, adds, “This study is yet another example of bridging physics and biology here in Dresden. Our interactive environment with biologists and theoretical physicists together ensures new interdisciplinary approaches to unravel the physics of biological processes.”

Animal studies on great apes have long been banned in Europe for ethical reasons. An alternative are so-called organoids, i.e. three-dimensional cell structures a few millimeters in size that are grown in the laboratory. These organoids can be produced from so-called pluripotent stem cells, which then differentiate into specific cell types, such as nerve cells. In this way, the research team was able to produce both chimpanzee brain organoids and human brain organoids. "These brain organoids allowed us to investigate a central question concerning ARHGAP11B" says Wieland Huttner of the MPI-CBG, one of the three lead authors of the study. "In a previous study together with Michael Heide, we were able to show that ARHGAP11B can enlarge a primate brain. However, it was previously unclear whether ARHGAP11B had a major or minor role in the evolutionary enlargement of the human neocortex. "To clarify this, the ARGHAP11B gene was either introduced into brain ventricle-like structures of chimpanzee organoids, or it was knocked out in human brain organoids, or the function of the ARHGAP11B protein was blocked by a related inhibitory protein. Would the ARGHAP11B gene lead to the proliferation of those brain stem cells in the chimpanzee brain that are necessary for the enlargement of the neocortex? "Our study shows that the gene in chimpanzee organoids causes an increase in relevant brain stem cells and an increase in those neurons that play a crucial role in the extraordinary mental abilities of humans," says Michael Heide, the study's lead author, who is head of the Junior Research Group Brain Development and Evolution at the DPZ, in collaboration with the MPI-CBG. When the ARGHAP11B gene was knocked out in human brain organoids or the function of the ARHGAP11B protein was inhibited, the amount of these brain stem cells decreased to the level of a chimpanzee. "We were thus able to show that ARHGAP11B plays a crucial role in neocortex development during human evolution," says Michael Heide. Adds Julia Ladewig of HITBR, the third of the lead authors: "Given this important role of ARHGAP11B, it is furthermore conceivable that certain maldevelopments of the neocortex may be caused by mutations in this gene."

Press Release of the German Primate Center

Only a small number of proteins have differences in the sequence of their amino acids – the building blocks of proteins – between modern humans and our extinct relatives, the Neandertals and Denisovans. The biological significance of these differences for the development of the modern human brain is largely unknown. In fact, both, modern humans and Neandertals, feature a brain, and notably a neocortex, of similar size, but whether this similar neocortex size implies a similar number of neurons remains unclear. The latest study of the research group of Wieland Huttner, one of the founding directors of the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, carried out in collaboration with Svante Pääbo, director at the Max Planck Institute for Evolutionary Anthropology in Leipzig, and Pauline Wimberger of the University Hospital Dresden and their colleagues, addresses just this question. The researchers focus on one of these proteins that presents a single amino acid change in essentially all modern humans compared to Neandertals, the protein transketolase-like 1 (TKTL1). Specifically, in modern humans TKTL1 contains an arginine at the sequence position in question, whereas in Neandertal TKTL1 it is the related amino acid lysine. In the fetal human neocortex, TKTL1 is found in neocortical progenitor cells, the cells from which all cortical neurons derive. Notably, the level of TKTL1 is highest in the progenitor cells of the frontal lobe.

Modern human TKTL1, but not Neandertal TKTL1, leads to more neurons in embryonic mouse neocortex
Anneline Pinson, the lead author of the study and researcher in the group of Wieland Huttner, set out to investigate the significance of this one amino acid change for neocortex development. Anneline and her colleagues introduced either the modern human or the Neandertal variant of TKTL1 into the neocortex of mouse embryos. They observed that basal radial glial cells, the type of neocortical progenitors thought to be the driving force for a bigger brain, increased with the modern human variant of TKTL1 but not with the Neandertal variant. As a consequence, the brains of mouse embryos with the modern human TKTL1 contained more neurons.

More neurons in the frontal lobe of modern humans
After this, the researchers explored the relevance of these effects for human brain development. To this end, they replaced the arginine in modern human TKTL1 with the lysine characteristic of Neandertal TKTL1, using human brain organoids – miniature organ-like structures that can be grown from human stem cells in cell culture dishes in the lab and that mimic aspects of early human brain development. “We found that with the Neandertal-type of amino acid in TKTL1, fewer basal radial glial cells were produced than with the modern human-type and, as a consequence, also fewer neurons,” says Anneline Pinson. “This shows us that even though we do not know how many neurons the Neandertal brain had, we can assume that modern humans have more neurons in the frontal lobe of the brain, where TKTL1 activity is highest, than Neandertals." The researchers also found that modern human TKTL1 acts through changes in metabolism, specifically a stimulation of the pentose phosphate pathway followed by increased fatty acid synthesis. In this way, modern human TKTL1 is thought to increase the synthesis of certain membrane lipids needed to generate the long process of basal radial glial cells that stimulates their proliferation and, therefore, to increase neuron production.

“This study implies that the production of neurons in the neocortex during fetal development is greater in modern humans than it was in Neandertals, in particular in the frontal lobe,” summarizes Wieland Huttner, who supervised the study. "It is tempting to speculate that this promoted modern human cognitive abilities associated with the frontal lobe."

Prof. Wieland Huttner (right) and Dr. Anneline Pinson (left) in the lab. Photo: MPI-CBG

These “condensates” resemble tiny drops, which are subject to the laws of biophysics, amongst other things. Unlike other cell organelles, condensates are not surrounded by a membrane. The very high protein concentration inside them stimulates biochemical reactions that would not be possible outside. Condensates form dynamically, sometimes in a matter of seconds, and are usually also rapidly degraded. When degradation is disrupted -–often due to aging – toxic substances can be deposited in affected cells, triggering degenerative diseases such as ALS or Alzheimer's disease. Hyman is now looking for new drugs that could cure these diseases.

Peter Tschentscher, First Mayor of the Free and Hanseatic City of Hamburg, says, “The Körber Prize for European Science has an outstanding international reputation and is one of the most highly endowed science prizes in the world. This year it will be awarded to Professor Anthony Hyman, a scientist who researches at the interface between biology and medicine in Hamburg's partner city Dresden. His scientific work can help to understand the causes of neurodegenerative diseases such as Alzheimer's or amyotrophic lateral sclerosis and to develop effective treatment options for these diseases.”

 “This year's Körber Prize succeeds in providing a fascinating insight into our most valuable asset ¬– our health. How we can best maintain our health is one of the great challenges facing society, and science has a crucial key role to play in solving it,” said Katharina Fegebank, Hamburg Senator for Science, Research, Equality and Districts. Anthony Hyman's pioneering work in the field of cell biology is one of these scientific impulses that significantly changes entire fields of research and creates new paths. His work impressively demonstrates that research with a spirit of inquiry and interdisciplinary exchange can open up previously unthinkable possibilities.

Anthony Hyman expressed his delight at the prestigious award, saying, “Neurodegeneration remains one of the greatest challenges in human health. Much of the work from my laboratory is focused on using physical chemistry concepts to understand how cellular processes fail in disease. It's a great honor and a real pleasure to be awarded the Körber Prize 2022 to further support these directions.”

The awardee
Anthony Hyman, 60, was born in the Israeli city of Haifa. After studying zoology at University College, London, he earned his doctorate at King's College Cambridge in 1987 on embryonic cell divisions of the nematode Caenorhabditis elegans. As a postdoctoral fellow, he went to the University of California in San Francisco. In 1993, Hyman became a group leader at the European Molecular Biology Laboratory in Heidelberg. In 1999, he was one of the founding members of the Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, which he still heads together with a team of directors. He has been a Fellow of the British Royal Society since 2007, an international member of the American National Academy of Sciences since 2020, and a member of the German National Academy of Sciences Leopoldina since 2021.

The Körber European Science Prize has honored outstanding scientists and scholars working in Europe for their forward-looking research work every year since 1985. Following the award of the Körber Prize, seven laureates have already received the Nobel Prize.

Portrait of Anthony Hyman and his research on the website of the Körber Foundation
Press release on the announcement of the Körber Prize on June 30, 2022

For a printed collection, 15 articles were selected and edited in a journalistic manner, which seemed particularly suited for publication from a science communication perspective and especially interesting for non-experts. MPI-CBG director Meritxell Huch is featured in this printed 2021 Yearbook Highlights collection with her research on liver organoids, published in Cell Stem Cell. Her chapter “Contacts in the liver” is highlight number 10 on page 28.

The highlights of the 2021 Yearbook shine a spotlight, amongst others, on the extent to which computer technologies have found their way into research; swarming phagocytes; contacts in the liver; virtual fusion plants; and the surprising history of our oral bacteria – just to name a few.

2021 Yearbook Highlights
MPI-CBG press release on the study in Cell Stem Cell

Cells need to be able to sense different types of signals, such as chemical and mechanical signals, from the environment to properly function. Most eukaryotic cells perform these functions through a specialised hair-like organelle, the cilium, that extends from the cell body as a sort of antenna. We smell through olfactory sensory cilia in our nose, we see through the photoreceptor cilia in our eyes and we hear thanks to kinocilia in our ears. Other cilia move in a beating fashion that for example allow us to breathe by keeping the lungs clean, or they allow us to reproduce by propelling sperm cells, and even to properly reason, because they contribute to the flow of fluids in the brain. Not surprisingly, defects in the assembly and function of these tiny organelles result in serious diseases, which are collectively known as ciliopathies. Thus, proper function of cilia is fundamental for human health.

A method to interfere with IFT trains
A bidirectional molecular transport system known as intraflagellar transport (IFT) is required for the proper assembly and function of cilia. IFT trains are propelled from the cell to the ciliary tip (anterograde direction) by kinesin-II motor proteins, where they unload the cargo needed for the assembly of the cilium before turning around and moving back to the cell (retrograde direction) driven by dynein motor proteins. The mechanism that coordinates the disassembly and reassembly of the IFT trains, which allows them to turn around, is unknown. It is commonly assumed that large protein complexes observed at the ciliary tip are responsible for this conversion of the IFT trains. Adrian Nievergelt, a postdoctoral researcher in the Pigino group, who is located at the MPI-CBG, jointly with Ludek Stepaneck, a former postdoc in the same team, have now developed a method to mechanically manipulate and stall IFT trains inside the cilia of the green alga Chlamydomonas at defined positions along the cilium. By observing the behaviour of these trains in a fluorescence microscope, they showed that such trains can readily change direction even at distance from the ciliary tip.

The researchers noticed that the IFT trains which convert and turn around at the tip do so slightly faster than when they get artificially stalled at any other spot. This brought up the question: is there a mechanistic difference between the two situations? In search of an answer, the group turned to cryo electron microscopy, a Nobel prize winning technology that uses high energy electrons to capture greatly magnified images of biological structures and reconstruct three dimensional tomographic representations at atomic resolution. These reconstructions of the cilia are noisy and hard for human eyes to interpret. Tim-Oliver Buchholz, a former member of the group of Florian Jug, now at the Human Technopole Computational Biology Research Centre and formerly located at MPI-CBG and the Center for Systems Biology Dresden (CSBD), applied his method cryo-CARE, a specifically trained neural network, to remove noise from the cryo-tomographic data. In one of the reconstructions, the scientists observed an exciting rare event of an IFT train in the process of walking off its rail at the flagellar tip. Adrian Nievergelt elaborates: “It was a revealing experience: once the noise was removed from the tomographic data, we could easily see how the very regularly structured IFT train falls apart and dissolves right after it passes the end of the microtubule it was running on.”

“It is striking how we can never observe an IFT train that changes direction twice. An explanation for this in Chlamydomonas is that the kinesin motors are no longer present on retrograde trains.” elaborates Gaia Pigino and concludes: “This discovery is an important step to solving the molecular mechanisms of how IFT trains convert in the cilium.”

Article in Italian; Human Technopole website

Researchers from the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany and from the Max Planck Institute for Biology in Tübingen, Germany have studied the roundworm (nematode) Pristionchus pacificus to investigate their adaptation on the island of La Réunion in the Indian Ocean with a range of temperatures from coast to summit. “My colleagues from the lab of Ralf Sommer from the MPI in Tübingen and I gathered nematodes on the island from several locations with various temperatures. Throughout our research, we discovered that Pristionchus pacificus from warmer coastal regions have higher fertility at warmer temperatures.  In contrast, Pristionchus pacificus from colder mountain regions have higher fertility at cooler temperatures,” explains Mark Leaver, the first author of the study, published in the journal Evolution. He continues, “This is the first study that systematically examined hundreds of these roundworm strains to measure fertility.” In order to illustrate the evolutionary relationships between the various strains of Pristionchus pacificus, the researchers also created a phylogenetic tree, a type of branching diagram that shows how closely the strains are related.

This study demonstrates how the nematode Pristionchus pacificus evolved to adapt to temperature changes, however it is currently unknown whether the populations on La Réunion can quickly enough adapt to ongoing climate change to live in their current geographic distribution. According to Mark Leaver, the study's findings “give useful information for models that could predict if this is the case, but further work is needed to find out.”

Photograph of Cirque de Cilaos on La Réunion habitat of Pristionchus pacificus and location of the study. Photo: Mark Leaver