Michael Lund Nielsen and his research group have shown that PARP1 does more than help detect DNA damage. The protein also regulates itself through a chemical modification known as auto-ADP-ribosylation. This modification changes the properties of PARP1 and appears to be crucial for determining when the protein is released from DNA. If PARP1 is not released correctly, it can block normal DNA replication and create additional stress in the cell.

The researchers will investigate how this mechanism affects the stress that arises when cancer cells copy their DNA, and how it can be used to improve the effect of existing PARP inhibitors, which are currently used to treat several types of cancer.

This has been a long development process, and with the technologies we now have, we can hopefully help improve patient treatment in the future, says Professor Michael Lund Nielsen.

Among other approaches, the research group will use advanced mass spectrometry to map the chemical modifications on PARP1. Mass spectrometry makes it possible to measure the structure, mass and quantity of molecules with high precision, making it a central tool in the project.

We have developed a mass spectrometric strategy that makes it possible to precisely identify the amino acids in PARP1 that are modified with ADP-ribose. There has long been uncertainty in the field about exactly where PARP1 is modified, and how these modifications help regulate the proteins interaction with DNA during replication of the genetic material. Our technology provides an unprecedented opportunity to systematically map these modifications and understand their biological significance, explains Michael Lund Nielsen.

The aim is to gain a better understanding of why some cancer cells respond to treatment with PARP inhibitors, while others develop resistance. In the longer term, the project may help identify new biomarkers and point towards more precise combination treatments for cancer patients.

The grant therefore supports research that can bring fundamental knowledge about DNA repair and replication stress closer to the cancer treatments of the future.

In 2016, PhD student Rasmus K. Jensen began developing a method to produce the CR3 receptor and the iC3b protein under the supervision of Professor Gregers R. Andersen. Two years would pass before it became possible to study the receptor and the protein at the molecular level at Aarhus University using electron microscopy. However, it was not Rasmus who ultimately determined the structure of iC3b bound to the receptor. New forces were needed. Josefine Lorentzen, who had just started as a PhD student at the time, took on the task. Rather than focusing on a smaller version of the iC3b protein called C3d, which can also bind to the receptor, she developed a clever way to stabilize the C3dCR3 complex. A breakthrough came during a stay in Hamburg, where she, for the first time, caught a glimpse of the structure that she and Rasmus had been chasing for so long. In spring 2024, Josefine achieved the final breakthrough. Suddenly, she and the rest of the research group understood in detail what happens when C3d binds to CR3.

Josefine describes the experience in her own words: It has been a project filled with both frustrations and small victories along the way. Many times, the goal felt very far away, but that is exactly why it was so fantastic when we could finally see the structure clearly. It felt like putting the final pieces into a puzzle we had been working on for years.

At the same time, she received help from postdoc Marlene U. Fruergaard to complete the work. In addition to studying the normal receptor, they investigated a variant that predisposes people to a rare hereditary autoimmune disease with the rather unwieldy name systemic lupus erythematosus.

Marlene explains: The structure of the disease-associated variant turned out to be almost identical to that of the healthy receptor, which tells us that it is not the binding to C3d itself that is affected by the mutation. The reason for the increased predisposition to the disease must therefore be linked to the receptor having a reduced ability to stimulate phagocytosis of the foreign cells. We hope to learn more about this in the coming years.

Gregers R. Andersen is very pleased: The course of this project illustrates what good basic research is built on: lots of talent, perseverance, technical advances and the ability to come up with fun ideas. But believe me, along the way we also went down many wrong paths. I am full of admiration for the efforts Rasmus, Josefine and Marlene have made.

Many modern drugs for treating, for example, cancer are based on antibodies and exploit the interaction between antibodies and iC3b to achieve effective phagocytosis of cancer cells. At the same time, experiments in mice suggest that iC3b-driven phagocytosis is overactive in connection with diseases such as Alzheimers and Parkinsons. The new research therefore has great potential to contribute to the development of even better drugs for treating cancer and alleviating these two feared neurological diseases.

The projects results have opened the door to many new initiatives and collaborations. In addition to Marlene, two PhD students are now following up on the new results with similar receptors and other techniques. Hopefully, they will not have to wait 10 years to see the fruits of their work.

Along the way, the project was supported by the Lundbeck Foundation, Alexion, the LEO Foundation, the Novo Nordisk Foundation and the Independent Research Fund Denmark.

Contact:

Gregers R. Andersen
Email: gra@mbg.au.dk

The CicerNord project will investigate how chickpeas can be adapted to the short growing seasons and climatic conditions in Denmark and the rest of Northern Europe. A key goal is to identify early-maturing chickpea varieties that can reach maturity before the wet Nordic autumn months reduce yield and quality. says Assistant Professor at Department of Molecular Biology and Genetics and project leader Aleksandr Gavrin.

The projects first field trial starts in week 19, when 150 chickpea accessions will be sown in a trial field located between Aarhus and Randers. This is an important step for the project, as the researchers expect to have the first indications within approximately four months of whether some of the accessions are suitable for cultivation under Danish conditions.

Danish farmers have already trialled chickpea cultivation, but they have faced challenges with a high proportion of immature green seeds and relatively low yields. One reason for this is the chickpea plants growth habit: the plants can continue growing as long as there is moisture in the soil, which delays seed maturation.

The researchers have access to a large collection of genetically diverse chickpeas: 398 varieties, landraces and breeding lines from around the world, all of which have already been genetically sequenced. A selected group of 150 genetically diverse chickpeas has been tested for seed quality, germination and vigour under conditions resembling those in central Jutland in late April. The results show surprisingly high cold tolerance, with 90% of the seeds germinating under cold conditions.

The project combines field trials, laboratory experiments and genetic analyses to identify the traits and genes that are important for early maturation, yield, nitrogen fixation and nutritional quality. Chickpeas can form symbioses with soil bacteria that fix nitrogen from the air. This can reduce the need for synthetic fertilisers and thereby lower the climate footprint of agriculture. The researchers will also investigate the nutritional quality of the chickpeas, including protein content and antinutritional compounds, and compare them with other protein crops such as soybeans and faba beans.

Industrial partners in the project will also assess how selected chickpea varieties perform in cooking, processing and food production, ensuring that future varieties meet the needs of both consumers and the food industry says Aleksandr Gavrin. In the long term, the project could provide farmers in Northern Europe with a new local protein crop that can strengthen food supply, reduce dependence on imports and open new markets for plant-based foods.

The aim is not to launch a finished variety immediately, but to establish an important foundation for the future breeding of chickpeas adapted to Nordic growing conditions says Aleksandr Gavrin.

The project has received a grant of DKK 3,997,284 from Plant2Food.

The project will pioneer the use of so-called time-resolved crystallography to observe protein kinases, which are key regulators of biological processes, in action, effectively creating "molecular movies" of how they work. 

The grant, funded through the NNF MicroMAX Collaborative Research programme, brings together a diverse group of experts in structural biology, plant science, and electron diffraction, with the aim of building a critical mass for future research in the area.

Watching biology as it happens

Proteins are often described as the machinery of life, but most structural studies capture them as static snapshots. 

In reality, proteins are dynamic says Ditlev Brodersen: 

Proteins move, change shape, and interact with other molecules in tightly coordinated sequences. This is especially true for protein kinases. These enzymes act as molecular switches, turning cellular processes on and off by attaching small chemical tags in the form of phosphate groups to other proteins. 

Proteins play essential roles across all forms of life, from bacteria to plants and animals, and are critical for human health. However, despite decades of research, scientists still lack a detailed understanding of how kinases perform these tasks step by step. 

Thats because weve mostly been looking at still images, explains Ditlev Brodersen, What we really need is a movie.

A new generation of structural biology

The new project aims to provide exactly that. Using advanced X-ray diffraction techniques at the MAX IV Laboratory in Lund, Sweden, home to the cutting-edge MicroMAX synchrotron beamline also funded by the Novo Nordisk Foundation, researchers will track structural changes in proteins as they happen in real time. 

Instead of analysing a single, large crystal, time-resolved methods rely on thousands of tiny crystals and extremely fast measurements. By initiating a reaction, such as adding the molecule ATP that fuels kinase activity, and capturing data at precise time points, scientists can reconstruct a sequence of structural changes. 

The result is a time-resolved view of protein function: A molecular movie rather than a single frame. To make the picture even richer, the team will combine X-ray data with electron-based diffraction. This complementary approach allows them not only to see how proteins move, but also to detect subtle changes in electrical charge, which are critical for understanding how chemical reactions take place.

From plant symbiosis to bacterial defence

The research will focus on two biological systems that illustrate the broad importance of kinases. One involves plants forming beneficial partnerships with nitrogen-fixing bacteria, an interaction essential for sustainable agriculture. Understanding how kinases regulate this process could help improve crop efficiency and reduce reliance on fertilisers. 

The other focuses on bacterial defence mechanisms against viruses, also known as bacteriophages. Here, certain kinases appear to play a role in shutting down cellular processes to prevent viral takeover. Insights into this system could deepen our understanding of microbial ecosystems and antiviral strategies aimed at improving our response to human infectious diseases. 

Although very different, both systems rely on the same fundamental principle: Precise control through phosphorylation, the chemical modification carried out by kinases.

Building a Danish hub for time-resolved studies

Beyond the scientific discoveries themselves, the project has a broader ambition: To establish Aarhus University as a leading centre for time-resolved structural biology.

The funding will support a team of young researchers, including postdoctoral fellows and a PhD student, working across multiple laboratories. The initiative builds on existing research infrastructure at AU, including crystallization facilities at MBG and advanced cryo-EM capabilities at EMBION, forming a strong technological foundation for time-resolved experiments with both X-rays and electrons. 

By integrating expertise in x-ray and electron crystallography, as well as and computational analysis, the project aims to create a critical mass of researchers skilled in these advanced techniques. Importantly, the work will also help develop methods and workflows that other scientists can adopt in the future, lowering the barrier to using time-resolved approaches.

With the new 7 m DKK grant, the research groups involved are set to play a central role in this transformation, advancing both fundamental science and the technologies that make it possible. The projects outcomes are expected to provide new insights into essential biological processes while training the next generation of scientists in one of the most exciting frontiers of modern biology.

Contact:

Professor Ditlev Egeskov Brodersen
deb@mbg.au.dk 

A hidden regulator in the brain

The researchers developed a mouse model in which the 3UTR part of Grin2b was removed, while the protein-coding sequence was left intact. The results were striking: the amount of mRNA remained unchanged, but the level of the corresponding protein, GluN2B, was reduced by half.

At the same time, the protein was significantly reduced in synapses - the contact points where neurons communicate. The mice showed clear signs of impaired synaptic signalling, lost the ability to form long-term potentiation (LTP), and performed worse in tests of spatial learning and memory.

This study shows that parts of our genes that are usually overlooked actually play a crucial role in how brain cells function, the researchers explain.

RNA as the cells GPS

The explanation lies in how mRNA functions in neurons. Although the 3UTR does not become protein, it acts as a kind of address code or GPS that ensures mRNA is transported to the correct locations within the cell - particularly to synapses.

Here, proteins can be produced locally, precisely where they are needed to strengthen or weaken connections between neurons. When this regulation is lost, protein synthesis occurs in the wrong place, weakening brain signalling.

More than just genes and proteins

The study highlights that gene function is not solely determined by protein-coding regions. The non-coding 3UTR plays a central role in regulating how and where proteins are produced.

This discovery may be key to understanding a range of neurological and psychiatric disorders. GRIN2B has previously been linked to conditions such as autism, epilepsy, intellectual disability, and schizophrenia.

New opportunities for treatment

The findings open a new direction in medical research. Rather than focusing only on proteins, researchers can now turn their attention to RNA and its regulatory role.

In the long term, this may lead to new treatment strategies aimed at restoring proper mRNA localisation or local protein synthesis in the brain. Such RNA-based therapies could potentially improve synaptic function without altering the gene itself.

A new layer of gene regulation

Overall, the study reveals a previously overlooked layer of gene regulation in the brain. While research has traditionally focused on genes and proteins, this work shows that RNA plays a far more active role than previously assumed.

This not only changes our understanding of the brain - but also how we may study and treat brain disorders in the future.

About the research

Type of study: Basic, preclinical neuroscience research

Collaborators:
International: Bevan Scott Main, Georgetown University
AU: Ulrik Bølcho, Anders Nykjær, Mai Marie Holm

Funding:
Novo Nordisk Foundation (0101095)
Danish National Research Foundation (DNRF133)

Competing interests:
The authors report no competing interests

Scientific article:
https://www.pnas.org/doi/10.1073/pnas.2518282123

Contact:
Associate Professor Magnus Kjærgaard
Department of Molecular Biology and Genetics
magnus@mbg.au.dk
 

Legumes also have the special ability to fix nitrogen from the air, thereby reducing the need for synthetic fertilizers. However, to fully realize this potential, the crops must be able to grow locally. This can be challenging in the Danish climate, where cold winters and dry springs can affect yields.

A new genetic breakthrough

Professor Stig Uggerhøj Andersen from the Department of Molecular Biology and Genetics at Aarhus University, Professor Tae-Jin Yang from Seoul National University, and Assistant Professor Murukarthick Jayakodi from Texas A&M University have recently published a study in Nature Genetics presenting a possible solution.

In the study, the researchers developed a significantly improved reference genome for faba bean and identified more than 35,000 genes. By analyzing hundreds of faba bean lines including both winter and spring types they identified a key genetic region called FR-1 (Frost Resistance 1) that determines the plants ability to survive frost.

Winter faba beans are sown during the winter season as the name suggests and harvested in autumn. Spring faba beans are sown in spring and, like winter varieties, harvested in autumn. Winter faba beans often establish a larger root system than spring types.

We have found that winter hardiness in faba beans is largely controlled by a specific genetic locus. In other words, the right allele at a particular location in the genome is crucial for whether the plant can survive the winter, explains Stig Uggerhøj Andersen.

The region contains genes that are activated at low temperatures and help the plant adapt to cold conditions.

Could lead to more stable yields

With this new knowledge, it may be possible to improve winter hardiness in faba beans so that the crop becomes more robust and better suited to cooler climates. If faba beans can be sown in winter, the plants can establish a strong root system before spring arrives. This can make them more resilient to both frost and drought, thereby increasing yield stability.

Yield stability is one of the biggest challenges when growing legumes. They are often perceived as more sensitive than other crops. If we can increase their resilience to drought and other climate challenges, it will become much more attractive for farmers to cultivate them, says Stig Uggerhøj Andersen.

In the long term, the results may help increase the production of plant-based protein in Europe and contribute to more sustainable agriculture.

Danish funding for the faba bean activities from GUDP has been crucial for the study. The Green Development and Demonstration Programme (GUDP) supported the IMFABA project directly and ProFaba through the European SusCropERA-NET Cofund programme, with Professor Stig Uggerhøj Andersen from Aarhus University serving as coordinator for both projects.

About the research

Study type:
Scientific publication

External funding:
Leibniz Association, European Unions Horizon 2020 Programme for Research & Innovation, Joint Programming Initiative on Agriculture, Food Security, and Climate Change, Green Development and Demonstration Programme (GUDP), Czech Science Foundation, Cooperative Research Program for Agriculture Science and Technology Development, National Research Foundation of Korea (NRF), Korea Atomic Energy Research Institute, ERDF Programme Johannes Amos Comenius.

Conflict of interest:
OS and GW are employees of NPZ Innovation (NPZi) GmbH. All other authors declare no competing interests.

Link to the scientific article:
Nature Genetics

Contact:
Stig Uggerhøj Andersen
Molecular plant genetics, Professor
Department of Molecular Biology and Genetics
sua@mbg.au.dk
 

Michael Lund Nielsens research focuses on protein composition and regulation, with particular emphasis on protein modifications and their functional significance. In this context, he will make use of MBGs mass spectrometry research infrastructure.

A key conceptual contribution from Michael Lund Nielsens research group has been to demonstrate that protein modifications do not merely function as static recruitment signals, but can also encode dynamic regulatory information - including timing, spatial organisation, and the order of biological processes.

His research has led to methodological and biological breakthroughs in mass spectrometry-based proteomics and protein modifications and has helped define international standards for mapping post-translational modifications.

More broadly, my research aims to establish mass spectrometry-based proteomics as a mechanistic biological discipline - moving beyond simply cataloguing proteins and modifications and instead defining regulatory principles that explain how protein networks function in space and time in both health and disease, explains Michael Lund Nielsen.

With his background in both academic research and technological development, he has extensive experience in building and leading large proteomics infrastructures as well as international research consortia.

As part of his appointment, Michael Lund Nielsen will serve as the scientific director of MBGs mass spectrometry core facility. The day-to-day operations will be managed by a dedicated facility manager, while his expertise in method development and advanced biological applications will enable a significant expansion of the facility for the benefit of researchers at MBG and across Aarhus University.

Michael Lund Nielsen sees this combination of research and infrastructure as particularly relevant for MBG, where proteomics can function as a shared enabling technology across research areas.

Alongside building my own research programme, I see proteomics as a central enabling technology for the department. A key focus at MBG will therefore be to anchor advanced mass spectrometry-based proteomics as a shared platform that supports and accelerates research across MBG - including disease-relevant and translational systems.

Academic background

Michael Lund Nielsen obtained his PhD in ion physics from Uppsala University. He subsequently continued as a postdoctoral researcher at the Max Planck Institute for Biochemistry in Martinsried, near Munich. In 2009, he took up a position as Associate Professor at the Novo Nordisk Foundation Center for Protein Research in Copenhagen and was appointed Professor there in 2014.

His work is widely cited and has had significant impact on both basic research and applied proteomics internationally.

Outside the laboratory, Michael enjoys spending time with his family and being in nature. He also has a long-standing interest in coffee and particularly enjoys brewing good espresso at home - a daily ritual that brings calm and a focus on quality and detail.

This ability, however, appears to function best in younger and middle-aged individuals.

It seems that in some older adults - we do not yet know whether this applies to everyone - this system does not function as well. This is likely due to changes in some of the DNA found in the mitochondria of muscle cells. These changes appear to play a role in the muscles ability to retrain, explains Tinna Stevnsner.

The researchers now aim to gain a deeper understanding of what these epigenetic changes actually entail.

What we are interested in is, first, what these epigenetic changes lead to, which molecular mechanisms are affected, and what it is that does not function optimally in older adults. At the same time, we want to investigate whether different types of exercise - for example strength training or endurance exercise - have different effects on this system, says Tinna Stevnsner.

In the long term, the results of the project may lead to more precise recommendations on which types of exercise are most beneficial for older adults - particularly for those who do not experience progress despite regular physical activity.

The research project is funded by the Novo Nordisk Foundation, which has awarded a total of DKK 17 million. Of this amount, DKK 15 million is earmarked specifically for the project.

This is an important recognition of our research, and it means that we can carry out the research we want to pursue - within a field in which we believe we have strong expertise, says Tinna Stevnsner with a smile.

The project will run for four years and will commence on 1 May 2026.