RSS feedhttps://mbg.au.dk/en/news-and-events/newsNews from the Department of Molecular Biology and Genetics, Aarhus University, Denmarken-gbFri, 29 Mar 2024 08:32:47 +0100Fri, 29 Mar 2024 08:32:47 +0100TYPO3 EXT:newsnews-76790Fri, 22 Mar 2024 07:20:00 +0100A new powerful toolbox may solve big questions in small synapseshttps://mbg.au.dk/en/news-and-events/news-item/artikel/a-new-powerful-toolbox-may-solve-big-questions-in-small-synapsesThe development of new cutting-edge techniques allows researchers to delve into the molecular architecture of one of the smallest structures in the brain – the synapses. This innovative approach is expected to yield important insights into the onset of several major brain disorders.Synapses between neurons are responsible for processing and storing information in the brain. Unlike many other organs in the body, synapses can change in shape and strength throughout life. As such they play a huge role in the homeostasis of the brain and proper brain function. 

For this reason, pathology at synapses can carry fatal consequences and it is well-known to be a common cause of major brain disorders such as Parkinson’s Disease and Schizophrenia.

Up until now, detailed investigation of the physiology of synapses using conventional light microscopy has been nearly impossible because of their sizes. With a measure of only a few hundred nanometers in diameter, they are comparable to the wavelength of light.

“Light cannot resolve objects that are below its wavelength. This is called the diffraction limit. Due to this diffraction limit, conventional microscopy cannot see clearly what’s inside synapses,” explains Associate Professor and DANDRITE Group Leader, Chao Sun.

In a new perspective just published in The Journal of Physical Chemistry, he describes a set of cutting-edge technologies that are so powerful they can visualize individual molecules at synapses.

“There is an increasing repertoire of techniques that allow us to resolve individual molecules in situ at synapses, such as super-resolution microscopy, cryogenic electron microscopy and tomography, and single-particle tracking.  These techniques make it possible for us to analyze the distribution, quantity, dynamics, structure, and function of individual molecules that reside inside synapses,” Sun states.

These in situ single-molecule techniques are beginning to transform our averaged knowledge of a synapse, promising exciting discoveries in subcellular biophysics of synapses and single-synapse proteomics.

In essence, these techniques serve as a crucial gateway to unlocking the inner workings of synapses, enabling a deeper understanding of their biological mechanisms in both health and disease contexts.

“With these techniques, many exciting new questions and challenges have emerged. This will undoubtedly lead to new findings in the coming years,” Chao Sun concludes.


SUPPLEMENTARY INFORMATION, INCLUDING CONTACT INFORMATION

We strive to ensure that all our articles live up to the Danish universities' principles for good research communication. Against this background, the article is supplemented with the following information:

Study type:

Experiment

External funding:

Lundbeckfonden grant no. R361-2020-2654 and the Novo Nordisk Foundation (NNF23OC0085864).

Conflicts of interest:

None

Link to the scientific article:

Single-Molecule-Resolution Approaches in Synaptic Biology

Chao Sun

Danish Research Institute of Translational Neuroscience - DANDRITE/
Department of Molecular Biology and Genetics, Aarhus University, Denmark;

The Journal of Physical Chemistry 

More information

Chao Sun
DANDRITE/Department of Molecular Biology and Genetics
Aarhus University, Denmark
chaosun@dandrite.au.dk

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ResearchRikke Skovgaard Lindhard17110884001711088400
news-76786Fri, 22 Mar 2024 06:01:00 +0100Esben Lorentzen appointed Professor in Computational Structural Biology https://mbg.au.dk/en/news-and-events/news-item/artikel/esben-lorentzen-appointed-professor-in-computational-structural-biologyEsben Lorentzen has been appointed Professor in Computational Structural Biology at the Department of Molecular Biology and Genetics at Aarhus University as of 1 May 2024. His research focuses on understanding the structure and mechanism of large protein complexes driving cellular organization and function.Esben Lorentzen’s research is dedicated to addressing critical challenges in molecular biology with a particular focus on intracellular transport mechanisms and cilium formation in eukaryotic cells. Cilia are cellular antennas that allow communication between cells to drive the development of organisms, and faulty cilia lead to a number of diseases such as kidney cysts, obesity, and blindness.

How cells construct slim hair-like ciliary organelles with specialized functions is still largely a mystery, but we know that it does require the assistance of large intraflagellar transport complexes that, with the help of molecular motors, ferry proteins in and out of the cilium. Both cilia, as ancient eukaryotic organelles, and intraflagellar transport, as a fundamental biological process, are evolutionarily conserved from single-celled green algae to humans. The research group of Esben Lorentzen uses structural biology techniques to unravel the mechanisms of how transport proteins assemble into very large complexes that organize cilia organelles in cells.

Emphasizing the growing significance of computational methods in molecular biology, the group led by Esben Lorentzen has adopted advanced machine-learning techniques to predict and design the structure of protein complexes. One notable achievement here is the recent publication of a structural model for the 15-subunit intraflagellar transport complex. This model has been pivotal in elucidating the distribution of cargoes and molecular motors, as well as enhancing our understanding of disease mutations through their mapping onto the structural model. As we move forward,  the research group led by Professor Esben Lorentzen will increasingly incorporate computational methods to design proteins with novel functions.


Esben Lorentzen – brief biography

Esben Lorentzen earned his PhD jointly from the European Molecular Biology Laboratories (EMBL) in Hamburg, Germany, and Aarhus University in 2004, focusing on the study of metabolic enzyme mechanisms under the supervision of Prof. Ehmke Pohl.

Following his doctoral studies, Esben Lorentzen shifted his focus to elucidating the mechanisms of RNA processing and degradation. He carried out postdoctoral research at the EMBL in Heidelberg, Germany, under the mentorship of Prof. Elena Conti, and at Birkbeck College in London, UK, guided by Prof. Helen Saibil. His work during this period involved the use of structural biology methods such as X-ray crystallography and single-particle cryo electron microscopy to determine experimental structures of RNA degrading exosomes.

In 2009, Esben Lorentzen assumed the role of Research Group Leader at the Department of Structural Cell Biology at the Max Planck Institute of Biochemistry in Martinsried, Germany. Here, he established himself as a leader in the fields of intracellular protein trafficking and cilium formation, funded by both the German research council and an ERC career grant.

In 2016, Esben Lorentzen received the Novo Nordisk Foundation Young Investigator award, which facilitated the transition of his research group to Aarhus University in Denmark. Here, he continued his structural and mechanistic studies of cilium formation as an Associate Professor at the Department of Molecular Biology and Genetics. The work of his research group includes the experimental structure determination of numerous protein complexes to elucidate their function in organizing the inner life of eukaryotic cells and understanding what goes wrong in cilium-related human diseases.

Esben Lorentzen actively engages in teaching biochemistry and structural biology courses at Aarhus University. He is the course responsible for Biomolecular Structure Determination where Master and Ph.D. students get a thorough introduction to structure determination using X-ray crystallography and cryo-electron microscopy, as well as structure prediction using machine-learning techniques such as AlphaFold.


More information

Esben Lorentzen
Department of Molecular Biology and Genetics
Aarhus University
Denmark
el@mbg.au.dk

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PeopleLisbeth Heilesen17110836601711083660
news-76760Fri, 22 Mar 2024 06:00:00 +0100Kasper Røjkjær Andersen appointed Professor in Plant Structural Biologyhttps://mbg.au.dk/en/news-and-events/news-item/artikel/kasper-roejkjaer-andersen-appointed-professor-in-plant-structural-biologyKasper Røjkjær Andersen has been appointed Professor in Plant Structural Biology at the Department of Molecular Biology and Genetics at Aarhus University as of 1 May 2024. His research focuses on understanding how plants form symbiosis with bacteria and fungi, and how to harness this ability to support the Green Transition.Kasper Røjkjær Andersen leads a research group at Aarhus University investigating how plants and microbes communicate. Their goal is to understand the various ways in which plants and microbes interact at the biochemical and molecular level. A major focus is on how plant cell-surface receptors perceive microbial signals and how this enables them to engage in symbiosis with nitrogen-fixing bacteria and phosphate-accruing fungi, while at the same time fight off pathogenic microbes.

The long-term goal is to expand our fundamental knowledge of how plants and microbes interact and how we can use this to develop new solutions and products to aid in the green transition and future sustainable agriculture. The research group utilizes advanced techniques to study the structure and function of proteins crucial for these interactions. They try to uncover the molecular innovations that enabled plants (100 million years ago) to evolve the nitrogen-fixing symbiosis out from the more ancient (450 million years ago) arbuscular mycorrhizal symbiosis. 


Kasper Røjkjær Andersen - brief biography

Kasper Røjkjær Andersen received his PhD from Aarhus University in 2009 under the supervision of Professor Ditlev Brodersen, studying detailed mechanisms of mRNA turnover. He was then a postdoc at Massachusetts Institute of Technology (MIT) in Boston, USA working on the structure and function of the Nuclear Pore Complex in the group of Professor Thomas Schwartz.

In 2014, he returned to Denmark and Aarhus University and set up his research group centered on understanding how plants form symbiosis with beneficial bacteria and fungi. He has contributed discoveries to the field of plant-microbe biology and especially on the molecular details of how the EPR3, NFR1, NFR5, and SYMRK receptors control symbiosis.

Kasper was one of the pioneers that brought nanobody technologies to Denmark, and his group has since developed many nanobody-based solutions to explore how plant receptors work at the molecular level. One of the major discoveries was that nanobodies could be used to modulate plant signaling and elucidate the receptor complex controlling symbiotic signaling.

Kasper is a partner in the ENSA program that aims to engineer nitrogen-fixing symbiosis into non-legumes such as cereals and cassava. ENSA is funded by the Bill and Melinda Gates Foundation and Bill and Melinda Gates Agricultural Innovation. He is also a partner of the InROOT and N2CROP programs funded by the Novo Nordisk Foundation that aim to develop a sustainable agriculture food systems.


More information

Professor Kasper Røjkjær Andersen - kra@mbg.au.dk
Department of Molecular Biology and Genetics
Aarhus University, Denmark

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PeopleLisbeth Heilesen17110836001711083600
news-76788Fri, 22 Mar 2024 05:59:00 +0100Bjørn Panyella Pedersen appointed Professor in Membrane Protein Biophysicshttps://mbg.au.dk/en/news-and-events/news-item/artikel/bjoern-panyella-pedersen-appointed-professor-in-membrane-protein-biophysicsBjørn Panyella Pedersen has been appointed Professor in Membrane Protein Biophysics at the Department of Molecular Biology and Genetics at Aarhus University as of 1 May 2024. His research focuses on understanding the molecular mechanisms that govern developmental plasticity in plant growth.Plants are the basis for terrestrial ecosystems, have dominating influence on atmospheric chemistry, and support all other organisms by using sunlight to convert water and carbon dioxide into sugars. Due to their fixed location, plant adaptability to environmental changes is essential for their survival, and plants are unique in their complex responses to external changes.

The focus of Bjørn's research is to understand the molecular mechanisms that govern developmental plasticity in plant growth. Understanding this process is crucial for coping with current and upcoming challenges in agriculture and environmental science, which will be essential for determining resilience of whole ecosystems.


Bjørn Panyella Pedersen - brief biography

Bjørn received his PhD from Aarhus University in 2008, where he unraveled the structure of the Proton Motive Force generating proton-ATPase from the model plant Arabidopsis. Subsequently, during a postdoctoral stay at the University of California - San Francisco, he investigated phosphate transporters from fungi that form symbiosis with plants, as well as the membrane transport of calcium that lies behind plant stress signaling, both processes that utilize the Proton Motive Force for transmembrane transport.

Supported by a fellowship from AIAS (Aarhus Institute of Advanced Studies), Bjørn returned to Denmark in 2014 to establish his research group at the Department of Molecular Biology and Genetics. His group focuses on proton-driven transmembrane transport processes in plants, particularly sugar, sterol, and plant-hormone transport. Their work sheds light on how these processes utilize proton gradients derived from the Proton Motive Force, enhancing our understanding of plant responses to the environment. Within this framework, the group elucidates how substrate specificity and affinity is achieved and how transport can be regulated and modified, essential cornerstones for rational design and augmentation of plant pathways.

Bjørn Panyella Pedersen's expertise in plant and fungal membrane protein biology has earned him international recognition, including prestigious awards such as ERC Starting and Consolidator Grants, DFF Sapere Aude, EMBO Young Investigator, Dupont Young Professor and a Hans Fischer Senior Fellowship . With a diverse and international research team currently representing 8 nationalities, Pedersen fosters collaboration and excellence in research.

Through his involvement with The Young Academy under the Royal Danish Academy of Sciences and Letters, Bjørn is an active advocate for academia, and he has contributed significantly to the national research discourse over the years in the press.

Read more about Bjørn's research


More information

Professor Bjørn Panyella Pedersen - bpp@mbg.au.dk
Department of Molecular Biology and Genetics
Aarhus University, Denmark

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PeopleLisbeth Heilesen17110835401711083540
news-76372Tue, 27 Feb 2024 11:00:00 +0100New discovery shows how cells defend themselves during stressful situationshttps://mbg.au.dk/en/news-and-events/news-item/artikel/new-discovery-shows-how-cells-defend-themselves-during-stressful-situationsA recent study by an international research team has unveiled an exciting discovery about how our cells defend themselves during stressful situations. The research shows that a tiny modification in the genetic material, called ac4C, acts as a crucial defender, helping cells create protective storage units known as stress granules. These stress granules safeguard important genetic instructions when the cell is facing challenges. The new findings could help shed light on relevant molecular pathways that could be targeted in disease.Stress granules are an integral part of the stress response that are formed from non-translating mRNAs aggregated with proteins. While much is known about stress granules, the factors that drive their mRNA localization are incompletely described. Modification of mRNA can alter the properties of the nucleobases and affect processes such as translation, splicing and localization of individual transcripts. The researchers show that the RNA modification N4-acetylcytidine (ac4C) on mRNA associates with transcripts enriched in stress granules and that stress granule localized transcripts with ac4C are specifically translationally regulated. They also show that ac4C on mRNA can mediate localization of proteins to stress granules. Their results suggest that acetylation of mRNA regulates localization of both stress-sensitive transcripts and RNA-binding proteins to stress granules and adds to our understanding of the molecular mechanisms responsible for stress granule formation.

Stress granules are membrane-less assemblies of mRNA-protein complexes that arise from mRNAs stuck in translation initiation. RNA-protein complexes are important for their formation and the mechanisms promoting stress granule formation involve both conventional RNA-protein interactions and interactions that encompass intrinsically disordered regions of proteins. Stress granules have been extensively studied, and it is well-established that they form when translation initiation is limited and a variety of roles for stress granules within the cell have been proposed. While stress granule assembly and disassembly can be regulated by various post-translational modifications the impact of RNA modifications on their formation, dispersal and function remains largely unclear.

The RNA modification N4-acetylcytidine (ac4C) has recently been shown to be deposited on mRNA and regulate translation efficiency. ac4C is conserved through all kingdoms of life and is induced upon several different stresses. ac4C is less abundant than other RNA modifications on mRNA and due to difficulties in precise and quantitative mapping its function and occurrence on mRNA has remained controversial.

The researchers show in their publication that ac4C is enriched in stress granules and that acetylated transcripts are predominantly localized to stress granules in response to oxidative stress, proposing a model where acetylation of RNA can affect mRNA localization to stress granules, in part by affecting the translational release of mRNA from the ribosome, providing new insight into both the function and consequences of mRNA acetylation and mechanism of RNA localization to stress granules.

The findings will promote the understanding of how the cells react to stress and which role RNA modifications play in the process. Both stress and RNA acetylation have implications in disease and their findings could help shed light on relevant molecular pathways that could be targeted in disease.

The project was led by Ulf A.V. Ørom’s lab at Aarhus University in Denmark, and the study involved collaboration with researchers from the University of Tartu, Norwegian Technical University, and the Max Planck Institute for Molecular Genetics in Berlin.

The findings have just been published in EMBO Reports.


SUPPLEMENTARY INFORMATION, INCLUDING CONTACT INFORMATION

We strive to ensure that all our articles live up to the Danish universities' principles for good research communication. Against this background, the article is supplemented with the following information:

Study type:

Experiment

External funding:

Lundbeck Foundation, Novo Nordisk Foundation, Carlsberg Foundation

Conflicts of interest:

None

Link to the scientific article:

N4-acetylcytidine (ac4C) promotes mRNA localization to stress granules

Pavel Kudrin, Ankita Singh, David Meierhofer, Anna Kuśnierczyk, Ulf Andersson Vang Ørom

Department of Molecular Biology and Genetics, Aarhus University, Denmark;
Institute of Biomedicine and Translational Medicine, University of Tartu, Estonia;
Department of Biomedicine, Aarhus University, Denmark;
Max Planck Institute for Molecular Genetics, Berlin, Germany;
Proteomics and Modomics Experimental Core (PROMEC), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology and the Central Norway Regional Health Authority, Trondheim, Norway.

EMBO reports: https://www.embopress.org/doi/full/10.1038/s44319-024-00098-6

For more information, please contact:

Associate Professor Ulf Andersson Vang Ørom
Department of Molecular Biology and Genetics
Aarhus University, Denmark
E-mail: ulf.orom@mbg.au.dk – Mobile: +45 2228 8766

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ResearchLisbeth Heilesen17090280001709028000
news-76067Tue, 13 Feb 2024 06:00:00 +0100Researchers uncover a key link in legume plant-bacteria symbiosishttps://mbg.au.dk/en/news-and-events/news-item/artikel/researchers-uncover-a-key-link-in-legume-plant-bacteria-symbiosisResearchers at Aarhus University have unveiled a groundbreaking discovery shedding light on the intricate play between legume plants and nitrogen-fixing bacteria. Their study, published in PNAS, details the crucial role played by phosphorylation in driving the formation of symbiotic organs, known as nodules, on plant roots. The long-term goal is to enable symbiosis in root nodules in important crops such as barley, maize and rice to avoid the use of chemical fertilizers.Legume plants have the unique ability to interact with nitrogen-fixing bacteria in the soil, known as rhizobia. Legumes and rhizobia engage in symbiotic relations upon nitrogen starvation, allowing the plant to thrive without the need for externally supplied nitrogen. Symbiotic nodules are formed on the root of the plant, which are readily colonized by nitrogen-fixing bacteria. The cell-surface receptor SYMRK (symbiosis receptor-like kinase) is responsible for mediating the symbiotic signal from rhizobia perception to formation of the nodule. The activation mechanism of the receptor was until recently unknown.

In this study, the researchers have now identified four essential phosphorylation sites that act as the catalyst for the symbiotic relationship between legume plants and nitrogen-fixing bacteria. The initial steps of the symbiotic pathway at the cell-surface are well-characterized, however, understanding of how the signal is relayed downstream has eluded the research field for years. The discovery of these essential phosphorylation sites is an important step towards translating the ability to form symbiotic relations with nitrogen fixing bacteria into crop plants.

“We knew that the receptor and its activity is essential for the establishment of symbiosis, but we didn’t know how or why. Phosphorylation is a common mechanism for regulating kinase activity, so we theorized that SYMRK function was tied to specific phosphorylations,” Nikolaj Abel explains.

Through collaborations with the lab of Ole Nørregaard Jensen at the University of Southern Denmark, several phosphorylation sites were identified in distinct regions of the SYMRK kinase. The researchers were able to narrow down the essential sites by depleting or mimicking phosphorylations in vivo. Specifically, four sites in the N-terminal region of SYMRK gave strong phenotypes when mutated.

“We explore the impact of site-specific mutations by creating receptor variants and reintroducing them into plants lacking the functional SYMRK receptor. Observing either spontaneous nodulation without rhizobia or the absence of nodulation despite their presence indicates that we’ve targeted an element crucial to the symbiotic pathway,” Nikolaj Abel elaborates.

To understand where the identified phosphorylation sites were situated on the SYMRK kinase, the researchers determined the structure of the intracellular domain of SYMRK.

“We needed to be able to map the phosphorylation sites onto a structural model of the SYMRK kinase to truly understand how these phosphorylation sites enable downstream signaling. We identified a structurally conserved motif in the N-terminal alpha-helical region which we termed ‘the alpha-I motif’. This region contains the four conserved phosphorylation sites,” Malita Nørgaard explains.

Enabling root nodule symbiosis in important crops is the aim

The long-term goal is to enable root nodule symbiosis in important crops like barley, maize and rice. These crops require large amounts of nitrogen fertilizers to grow, resulting in enormous CO2 footprints and making small-holder farmers unable to produce stable yields.

With the successful identification of phosphorylation sites crucial to initiating the nodulation program in legume plants, the researchers believe this newfound knowledge holds promising implications for translating nitrogen-fixing traits into crops.

Link to the article: 10.1073/pnas.2311522121


For more information, please contact

Postdoc Dr. Nikolaj Birkebæk Abel - nikolaj.abel@mbg.au.dk
PhD-student Malita Malou Malekzadeh Nørgaard - malitamn@mbg.au.dk
Associate Professor Kasper Røjkjær Andersen - kra@mbg.au.dk

Department of Molecular Biology and Genetics
Aarhus University, Denmark


SUPPLEMENTARY INFORMATION, INCLUDING CONTACT INFORMATION

We strive to ensure that all our articles live up to the Danish universities' principles for good research communication. Against this background, the article is supplemented with the following information:

ITEMS

CONTENT AND PURPOSE

Study type

Experiment

External funding

This work is funded by the project Molecular Mechanisms and Dynamics of Plant-microbe interactions at the Root-Soil Interface (InRoot), supported by the Novo Nordisk Foundation (NNF19SA0059362) and by the project Enabling Nutrient Symbioses in Agriculture (ENSA), that is funded by Bill & Melinda Gates Agricultural Innovations (INV- 57461), the Bill & Melinda Gates Foundation and the Foreign, Commonwealth and Development Office (INV-55767). Mass spectrometry research at the University of Southern Denmark is supported by the VILLUM Center for Bioanalytical Sciences (7292), PRO-MS: Danish National Mass Spectrometry Platform for Functional Proteomics (5072-00007B) and INTEGRA (NNF20OC0061575).

Conflicts of interest

Nikolaj B. Abel, Malita M. M. Nørgaard, Simon B. Hansen, Kira Gysel, Jens Stougaard & Kasper R. Andersen are inventors on a patent that captures these discoveries. Phosphorylation of the alpha-I motif in SYMRK drives root nodule organogenesis

Link to scientific paper

Nikolaj B. Abel, Malita M. M. Nørgaard, Simon B. Hansen, Kira Gysel, Ignacio A. Diez, Ole N. Jensen, Jens Stougaard,

and Kasper R. Andersen.

Phosphorylation of the alpha-I motif in SYMRK drives root nodule organogenesis

PNAS

10.1073/pnas.2311522121

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ResearchLisbeth Heilesen17078004001707800400
news-75877Wed, 24 Jan 2024 09:46:00 +0100Interdisciplinary study to explore bacteria's role in boosting low nitrogen input from the soil for cereal growthhttps://mbg.au.dk/en/news-and-events/news-item/artikel/interdisciplinary-study-to-explore-bacterias-role-in-boosting-low-nitrogen-input-from-the-soil-for-cereal-growthNSECURE, a new interdisciplinary project led by Simona Radutoiu at the Department of Molecular Biology and Genetics, Aarhus University, has been awarded DKK 15 million by the Novo Nordisk Foundation. This collaborative project also involves Associate professor Marianne Glasius (Chemistry, Aarhus University), and Professor Rasmus Waagepetersen (Mathematics, Aalborg University) and aims to study sustainable methods to optimise the yield of cereal crops by utilising soil bacteria.Crops such as wheat and barley heavily depend on nitrogen fertilizers to compensate for inadequate nitrogen levels in the soil. Typically, this compensation involves the use of chemical fertilizers, which unfortunately have a substantial negative impact on the environment. One potential sustainable solution is the utilization of biological nitrogen fixation facilitated by inoculants, which are nitrogen-fixing bacteria naturally present in the soil. However, the introduction of these bacteria to the soil poses challenges, hindering its viability as a long-term solution.

In addressing this issue, scientists from Aarhus University and Aalborg University are committed to developing a solution that not only benefits farmers but also prioritizes sustainability. The NSECURE initiative aims to identify the factors restricting the performance of these beneficial bacteria in soil and intends to create innovative tools for implementing reliable and resilient solutions for sustainable agriculture. The project brings together expertise from three diverse fields: chemistry, mathematics, and molecular biology. The collaboration across these disciplines is crucial for comprehending the intricacies of this biological challenge.

Professor Radutoiu emphasizes: "Together, we have unravelled how legume plants maintain a conducive microbial environment around their roots, fostering a beneficial, symbiotic relationship with nitrogen-fixing bacteria. This grant enables us to apply our collective knowledge and capabilities, transcending disciplinary boundaries, to tackle the task of establishing a similar microbial environment in the root zone of cereals. This will enable beneficial bacteria to thrive and contribute to the fixation of atmospheric nitrogen for their plant hosts."


For further information, please contact

Professor Simona Radutoiu
Department of Molecular Biology and Genetics
Aarhus University
radutoiu@mbg.au.dk

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GrantLisbeth Heilesen/Taylor Grace Fitzgerald17060859601706085960
news-75861Mon, 22 Jan 2024 06:00:00 +0100Students test a new method in Africa for diagnosing malariahttps://mbg.au.dk/en/news-and-events/news-item/artikel/students-test-a-new-method-in-africa-for-diagnosing-malariaTrine Juul-Kristensen and Celine Thiesen, Master's students at the Department of Molecular Biology and Genetics (MBG) at Aarhus University, are testing a new method based on saliva samples for diagnosing malaria at the Centre de Recherches Médicales de Lambaréné in Gabon in Africa as an integral part of their studies.ResearchKnowledge exchangeLisbeth Heilesen17058996001705899600news-75817Tue, 16 Jan 2024 11:37:04 +0100Cryo-microscopy reveals nano-sized copy machine implicated in origin of lifehttps://mbg.au.dk/en/news-and-events/news-item/artikel/cryo-microscopy-reveals-nano-sized-copy-machine-implicated-in-origin-of-life-1RNA is thought to have sparked the origin of life by self-copying. Researchers from Aarhus University, Denmark, and MRC LMB Cambridge, England, have revealed the atomic structure of an "RNA copy machine" through cryo-EM. This breakthrough sheds light on a primordial RNA world and fuels advancements in RNA nanotechnology and medicine.How the intricate molecular machinery of life arose from simple beginnings has been a long-standing question. Several lines of evidence point towards a primordial"RNA world", where an "RNA copy machine" (a so-called replicase) started making copies of itself and other RNA molecules to kick-start evolution and life itself. However, the ancient replicase appears to have been lost in time and its role in modern biology has been taken over by more efficient protein machines. To support the RNA world hypothesis, researchers have been seeking to re-create an equivalent of the RNA replicase in the laboratory. While such molecular “Doppelgangers” of the ancient replicase have been discovered, both their detailed molecular structure and mode of action has remained elusive due to the difficulty of determining the structure of dynamic RNA molecules.

Structure of an ice-loving RNA replicase

In a research paper published in PNAS, a team of researchers now report the first atomic structure of an RNA replicase using cryogenic electron microscopy (cryo-EM). The RNA replicase being studied was developed by the Holliger lab (MRC LMB Cambridge, UK) to be efficient at copying long templates using nucleotide triplets in the eutectic ice phase (similar to slush-ice). Returning from postdoctoral studies in the Holliger lab, Emil L. Kristoffersen, currently assistant professor at Aarhus University, facilitated a collaboration with the Andersen lab (Aarhus University, Denmark) to determine the structure of the RNA replicase by cryo-EM. Interestingly, the structure shows striking similarities to protein-based polymerases with domains for template binding, polymerization, and substrate discrimination arranged in a molecular shape resembling an open hand.

"It was surprising to find that a ribozyme that we evolved artificially in the test tube would display features of naturally occurring protein polymerases. This indicates that evolution can discover convergent molecular solutions no matter if the material is RNA or protein", explains Philipp Holliger, program leader at MRC LMB Cambridge, UK.

Model for RNA synthesis in an RNA world

To better understand how the RNA replicase works, the researchers did a comprehensive mutational study to highlight the crucial elements of the RNA structure. This analysis confirmed features of the catalytic site but also revealed the importance of two so-called kissing-loop interactions, which bind the scaffolding and the catalytic subunits together, as well as the importance of a specific RNA domain for fidelity, that is the accuracy with which the replicase copies RNA strands. While the researchers could not determine the structure of the replicase “in-action” while actively copying RNA, it was possible to build a model for RNA-based RNA copying that is consistent with all experimental data.

"Cryo-EM is a powerful method for studying the structure and dynamical features of RNA molecules. By combing cryo-EM data with experiments, we were able to build a model of the inner workings of this complex RNA machine", tells Ewan McRae, who did the cryo-EM work as a postdoc in the Andersen lab at Aarhus University but has now started his own research group at Houston Methodist Research Institute, Texas, USA.

Inspiration for RNA nanotechnology and medicine

The study provides an exciting first glimpse of an RNA replicase thought to reside at the very root of the tree of life. The currently developed RNA-based replicases are however very inefficient (as compared to protein-based polymerases) and cannot yet sustain their own replication and evolution. The structural insight provided by the reported study may help in designing more efficient replication mechanisms and thus get us closer to developing RNA world scenarios in the test tube.

"The properties of RNA replicases may be further improved by using chemical modifications that could exist in an RNA world. In addition, research into the origin of life leads to the discovery of several novel RNA building blocks that may be used in the emerging field of RNA nanotechnology and medicine", explains Ebbe Sloth Andersen, associate professor at Aarhus University, Denmark.


Additional information

Funding:

The research was funded by Independent Research Fund Denmark (9040-00425B), Novo Nordisk Foundation (NNF21OC0070452), Canadian Natural Sciences and Engineering Research Council (532417), Carlsberg Foundation (CF20-0635, CF17-0809), Lundbeck Foundation (R250-2017-1502), Medical Research Council, as part of United Kingdom Research and Innovation (also known as UK Research and Innovation (UKRI)) (MC_U105178804), Volkswagen Foundation (96 755), Herchel Smith studentship (2017), and Marie Curie fellowship (H2020-MSCA-IF-2018-845303).

Link:

Cryo-EM structure and functional landscape of an RNA polymerase ribozyme
Ewan K. S. McRae, Christopher J. K. Wan, Emil L. Kristoffersen, Kalinka Hansen, Edoardo Gianni, Isaac Gallego, Joseph F. Curran, James Attwater, Philipp Holliger, and Ebbe S. Andersen
Proceedings of the National Academy of Sciences (PNAS) Vol. 121, No. 2 (January 9, 2024) https://doi.org/10.1073/pnas.2313332121

Contact:
Ebbe Sloth Andersen
iNANO/Department of Molecular Biology and Genetics
Aarhus University
Email: esa@inano.au.dk - Phone: +45 41178619

Philipp Holliger
Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK
E-mail: ph1@mrc-lmb.cam.ac.uk
Phone: +44 1223 267092

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ResearchLise Refstrup Linnebjerg Pedersen17054014241705401424
news-75820Tue, 16 Jan 2024 11:23:00 +0100Biology Olympiad semi-final held at the Department of Molecular Biology and Geneticshttps://mbg.au.dk/en/news-and-events/news-item/artikel/biology-olympiad-semi-final-held-at-the-department-of-molecular-biology-and-geneticsThis week, the semi-finals of the Biology Olympiad were held for the 30 most talented upper secondary school students in biology in Denmark. The top 15 will advance to the final, where the top four will represent Denmark at the International Biology Olympiad, which this year will be held in Kazakhstan from 7-14 July 2024.The semi-final includes a theoretical test and two practical experiments prepared by university staff. At the Department of Molecular Biology and Genetics (MBG), Gregers Rom Andersen was responsible for the practical aspects of the semi-final. In this year's semi-final, the students had to examine the peptide semaglutide, which is the active ingredient in the drugs Ozempic , Rybelsus and Wegovy.

Gregers Rom Andersen: "Our department has also been part of the semi-final before, and it is a great pleasure to see how skilful these young people are with the exercises we have prepared for them. There is no doubt that they are among the best at biology at upper secondary school level in Denmark, and of course we hope that they will choose one of our programmes in molecular biology or molecular medicine."

The National Biology Olympiad in Denmark consists of a school round, a semi-final, a final and some training rounds. Gradually, the number of participants is reduced from many in the school round to the top 30 in the semi-final, top 15 in the final and the four winners who will represent Denmark at the IBO.

Each round includes a written test in biology and biotechnology subject areas such as cell biology, biochemistry, physiology, ecology, genetics and evolution. The semi-finals and finals also include several practical laboratory experiments. The training rounds cover areas of biology that are not part of the daily biology/biotech lessons and students are expected to prepare for these.

The International Biology Olympiad (IBO) is a competition in theoretical biology and practical laboratory exercises for students from all over the world. Participants are high school students with an interest in biology and biotechnology who have not reached the age of 20 by 1 July of that year and who are winners of their national Biology Olympiad.

The ScienceOlympiad consists of six independent national Olympiads in biology, computer science, physics, geography, chemistry and maths. The Olympiads are held annually, and all upper secondary education programmes in Denmark are invited to participate. The purpose of the ScienceOlympics is to encourage young scientific talents to develop their skills, interest and knowledge of science together with other talented young people.

Source: Biologiolympiaden Danmark

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PeopleLisbeth Heilesen17054005801705400580