DKK 39.6 million for NAT researchers’ own ideas

Obesity, symplectic structures, cancer, molecular diagnostics, fungal infections, liver disease, molecular machines, mathematical theory, brain cells and much more will now form the starting point for 11 new research projects.

The Independent Research Fund Denmark has awarded more than DKK 584 million through its largest funding scheme, DFF Research Project1. The funding has been distributed across a total of 167 grants.

Chair of the Fund’s Board, Søren Serritzlew, says:

“When researchers are given the opportunity to ask their own questions and pursue the ideas with the greatest potential, we cannot know in advance where the research will lead us. That is precisely one of the strengths of independent research: it can open up new areas of research, challenge what we think we know and generate insights that we could not have asked for in advance.”

At SDU, a total of 24 researchers have received one of these grants. This accounts for 14,37 per cent of the 167 grants awarded through the scheme in this round.

In 2025, four NAT researchers received a total of DKK 12.5 million. Read more here. 

In 2024, 10 NAT researchers received approximately DKK 31.4 million. Read more here.

At the Faculty of Science, the following researchers have received funding:

Kumar Somyajit, Department of Biochemistry and Molecular Biology. DKK 3,667,680 for the project Replisome dosage control from developmental adaptation to genome-doubled cancer.

Cancer cells often develop abnormal numbers of chromosomes. One dramatic route to this is whole-genome doubling, in which a cell suddenly acquires an extra copy of all its DNA. This is common in aggressive cancers and can help tumours evolve, resist treatment and survive stress. However, whole-genome doubling also creates a major challenge: the cell must copy and maintain twice as much DNA every time it divides. This project will investigate how whole-genome-doubled cells overcome this dosage constraint. We will examine the DNA replication machinery, focusing on PCNA, a key ‘sliding clamp’ that coordinates DNA replication and repair. Our recent work identified PAF15 as a key factor that helps PCNA function on chromatin, but only within a narrow dosage range: too little PAF15 impairs DNA replication, while too much can disrupt replication and kill cells. Using advanced microscopy, genome editing, stem-cell models and deep chromatin-resolved proteomics, we will track cells following whole-genome doubling. By comparing normal cells, cancer cells and embryonic stem-cell-based models, we will identify limiting factors in DNA replication and determine how cells adapt. The project may also uncover a new vulnerability in cancer. If aggressive cancer cells depend on high PCNA activity, PAF15-derived molecules could potentially force PCNA into a harmful, locked state, providing a basis for treatments that specifically target replication-dependent cancer cells. 

Søren Fisker Schmidt, Department of Biochemistry and Molecular Biology. DKK 3,672,000 for the project A senescence-associated adipose progenitor cell state as a driver of MASLD progression.

Adipose tissue is not simply a passive store of energy. It plays an active role in regulating the body’s metabolism and communicates closely with other organs, including the liver. In people with obesity and metabolic liver disease, adipose tissue often becomes dysfunctional, but it remains unclear which specific cell types within the tissue drive this process. Recent studies have identified a rare group of progenitor cells in human adipose tissue that show signs of cellular ageing and inflammation. These cells are more abundant in people with severe cardiometabolic forms of metabolic dysfunction-associated steatohepatitis (MASH) and may actively contribute to harmful communication between adipose tissue and the liver. However, it is still unclear whether these cells simply reflect the presence of disease or play a direct, causal role. This project aims to test whether inducing this specific cell state in adipose tissue is sufficient to disrupt the body’s metabolic balance and promote liver disease. By combining advanced genomic analyses with targeted genetic manipulation in experimental models, the project will identify key regulatory factors that define this cell state and investigate their functional significance in living organisms. A better understanding of how dysfunctional adipose tissue progenitor cells affect whole-body metabolism could provide new insights into the early mechanisms underlying cardiometabolic MASH.

Jan Oskar Jeppesen, Department of Physics, Chemistry and Pharmacy. DKK 3,654,720 for the project Electrically Controlled Cargo Release in [2]Rotaxanes via Mechanochemical Retro Diels-Alder Reactions.

Life depends on tiny “machines” inside our cells that keep everything moving and functioning. These molecular machines are incredibly small – so small that they operate at the level of individual molecules – and nature has refined them over billions of years. In this project, we aim to develop artificial molecular machines that can perform useful tasks when activated by electricity. More specifically, we will create systems capable of releasing small molecules, such as drugs, in a controlled and predictable manner. Our research focuses on structures called [2]rotaxanes. A rotaxane is an interlocked molecule consisting of a ring threaded onto a dumbbell-shaped “axle”, with large end groups that prevent the ring from slipping off. Because the ring can move along the axle, it can function as a simple molecular machine. When the rotaxane is exposed to an electrical signal, its charge distribution changes, causing the ring to move in a particular direction. This movement can generate mechanical force within the molecule. We will use this force to break a chemical bond and release a molecule attached to the rotaxane. In this way, an electrical signal is converted into a precise chemical reaction. If successful, this approach could lead to new technologies for targeted drug delivery, in which medicines are released precisely where and when they are needed, as well as advanced diagnostic tools that respond to small electrical signals.

Susanne Mandrup, Department of Biochemistry and Molecular Biology. DKK 3,672,000 for the project Revisiting the regulating of leptin gene expression: From transcription to energy homeostasis.
Leptin is a hormone produced primarily in the body’s fat cells and plays an important role in regulating appetite, energy expenditure and metabolism. A lack of this hormone leads to extreme obesity, but studies suggest that a moderate reduction in its expression may inhibit the development of metabolic diseases. The hormone was discovered in the 1990s, but despite its central importance to the body’s energy balance, we still know surprisingly little about how leptin expression is regulated in fat cells. New studies from our laboratory have revealed previously unknown sequences in the genome that appear to be important in this regulation. Deleting these sequences in mice leads to dysregulation of the leptin gene. In this project, we will build on these exciting findings to identify the key molecular mechanisms that control leptin gene expression. We will investigate the role of the newly discovered regulatory sequences in 1) fat stem cells, where they prepare the leptin gene for subsequent activation; 2) regulating the leptin gene in response to changes in fat-cell size and metabolic regulation; and 3) the regulatory feedback mechanism between adipose tissue and the brain’s control of appetite. The project is expected to lead to a breakthrough in our understanding of how the leptin gene is regulated. In the long term, we expect this knowledge to be useful in developing therapeutic strategies for modulating leptin expression to treat cardiometabolic diseases.

Martin Røssel Larsen, Department of Biochemistry and Molecular Biology. DKK 3,651,840 for the project Sialic acids in cortical development – A guide through space and time.
How the human brain organises itself during early development remains one of biology’s major unanswered questions. In this project, we will investigate how sialic acids – small, negatively charged sugar molecules found on the surface of cells – influence how brain cells migrate, organise themselves and communicate during the formation of the cerebral cortex. Although sialic acids are present at very high levels in the nervous system, their precise function in human brain development remains poorly understood. Using advanced mass spectrometry, spatial transcriptomics, bioimaging and human mini-brains grown from stem cells, we will map how sialylation changes over time and space during early neural development and brain-cell migration. Our preliminary data show that changes in sialylation have a marked effect on cortical organisation and neuronal migration, while the addition of the human sialic acid Neu5Ac has a major impact on the development of mini-brains. The project combines glycobiology, neurobiology and systems biology to create the first spatial and temporal atlas of sialylation during human cortical development. The results will provide fundamental new insights into the molecular mechanisms that govern the formation of the human brain.

Ralf Zimmerman, Department of Mathematics and Computer Science. DKK 3,215,520 for the project Riemannian Computing for Symplectic Structures.
Symplectic structures play a central role across science and technology. They arise naturally in classical and quantum mechanical theory, in quantum optics and in quantum computing. In computer simulations, symplectic structures ensure the conservation of energy, one of nature’s most fundamental properties. When computational costs are critical, low-rank data matrices are particularly important. However, the geometry of the space of symplectic low-rank matrices is still not sufficiently understood. We lack so-called normal coordinates for data processing under the standard method for measuring angles and lengths, yet this is precisely what determines the shortest connections between data points. To underline its importance: can we imagine more fundamental operations than “+” and “−”? In non-linear spaces, once we know the shortest connections, we can define non-linear counterparts to “+” and “−”. Without this knowledge, this is impossible. Today, development is driven by “trial and error” rather than by a solid theoretical understanding. This project aims to change the status quo by closing fundamental gaps in the theory of symplectic low-rank matrices. With this knowledge, we expect to be able to classify existing computational tools according to their numerical properties, as well as develop new methods with targeted and documented properties. All computational tools will be implemented in a publicly available code package for high-performance computing on non-linear spaces.

Brage Storstein Andresen, Department of Biochemistry and Molecular Biology. DKK 3,672,000 for the project Two Faces of 5′-UTR Pseudoexon Splicing: From Pathogenesis to Therapeutic Modulation.
The project will investigate a new strategy for increasing gene expression by modulating pseudoexon (PE) splicing in the 5′ untranslated region (5′ UTR). The central concept is that the inclusion or skipping of PEs can alter the architecture of upstream open reading frames (uORFs) and thereby relieve translational repression. We hypothesise that splice-switching oligonucleotides (SSOs) can modulate the splicing of selected 5′ UTR PEs, disrupt inhibitory uORFs and increase protein production from therapeutically relevant genes. This is particularly valuable in haploinsufficient diseases, where increased expression from the normal allele can compensate for reduced activity from the disease allele. We will identify SSO-modulatable 5′ UTR PEs in human disease genes, focusing on the CNS, where increased expression has therapeutic potential, and determine how altered 5′ UTR PE splicing affects uORF-mediated regulation of translation. In parallel, we will test whether disease-associated variants cause disease by altering 5′ UTR PE splicing in ways that change uORF architecture and reduce translation. Because most PEs are not annotated, such variants are likely to be underdiagnosed. The project will provide mechanistic insights into 5′ UTR PE splicing and uORF-mediated regulation, as well as identify specific opportunities for SSO-based therapies. The project will also establish an online tool for predicting the pathogenic effects of 5′ UTR sequence variants, thereby improving molecular diagnostics in clinical genetics.

Ole Nørregaard Jensen, Department of Biochemistry and Molecular Biology. DKK 3,672,000 for the project Decoding Histone Proteoform Dynamics Across the Cell Cycle and Disease States.
All human cells contain the same genes, but cells can function very differently because proteins are chemically modified and regulated after they are produced. These different versions of proteins are known as “proteoforms” and constitute the functional molecules that govern biological processes. Histone proteins are particularly important because they organise DNA and regulate which genes are active. Histones carry numerous chemical modifications that change dynamically during normal cellular processes and in diseases such as cancer. This project will investigate how histone proteoforms change throughout the cell-division cycle and how they are affected in aggressive brain cancer. We will develop highly sensitive analytical methods based on advanced mass spectrometry that can identify and quantify intact histone proteoforms in cells and tumour tissue in unprecedented detail. First, we will establish new methods for analysing intact histone proteins and their chemical modifications. We will then map how histone proteoforms change over time as cells divide. Finally, we will analyse histone proteoforms in tumour biopsies from patients with glioblastoma to identify cancer-specific molecular patterns. The project will provide new knowledge about how chromatin and gene regulation are controlled in healthy and diseased cells. In the longer term, the results could contribute to the development of new biomarkers and treatments for cancer and other diseases.

Jens Kaad, Department of Mathematics and Computer Science. DKK 3,536,640 for the project The local quantum index theorem.
One of the primary challenges for mathematics in the 21st century is to describe how geometry works at the atomic and subatomic level. At these scales, the tools of classical geometry can no longer be used because the laws of quantum mechanics conflict with our usual understanding of time and space. This led Fields Medalist Alain Connes to develop the profound mathematical theory known as “noncommutative geometry”, where “noncommutative” means that the order of the factors matters when two things are multiplied. “Noncommutative” is also a mathematical synonym for the more familiar word “quantum”. Noncommutative geometry has its roots in classical geometry, but also represents a dramatic extension of these ideas through its applicability to geometrical situations in which no spatial models exist. One of the cornerstones of noncommutative geometry is known as the “local index theorem”, which provides us with an extremely powerful computational tool. The local index theorem is also a groundbreaking extension of the Atiyah-Singer index theorem, regarded as one of the absolute high points of 20th-century mathematics. However, our need to understand quantum phenomena is constantly growing, and a number of limitations of the local index theorem have recently become apparent. The aim of this project is to prove a Local Quantum Index Theorem that can be applied to a number of important cases that lie beyond the scope of the local index theorem.

Panagiotis Galanos, Department of Biochemistry and Molecular Biology. DKK 3.672.000 for the project Defining the p21-PCNA replication stress survival checkpoint in lung cancer evolution.
Lung cancer remains one of the deadliest forms of cancer, partly because some cancer cells survive treatment and later return in a more aggressive form. One possible reason is replication stress, which makes it difficult for cancer cells to copy their DNA correctly. Normally, this should cause the cells to stop growing or die. However, some cancer cells, particularly those lacking the tumour suppressor p53, survive, enter a dormant-like state and may later escape from it. This may contribute to relapse and treatment resistance.
The project investigates how these cancer cells survive. We focus on the protein p21, which normally slows down cell division. Our results suggest that in stressed cancer cells, p21 may instead help them survive by binding to PCNA, a key protein involved in DNA replication. We propose that this p21-PCNA interaction acts as a survival checkpoint. The project will uncover how this checkpoint controls DNA replication, DNA repair and the choice between survival and cell death.
Using advanced microscopy and patient-derived 3D ‘mini-tumour’ cultures, we will investigate whether this mechanism can be exploited to make treatment-resistant cancer cells more vulnerable. In the longer term, this knowledge could contribute to new strategies for preventing lung cancer relapse.

Daniel Wüstner, Department of Biochemistry and Molecular Biology. DKK 3,491,880 for the project Development and validation of novel antifungal polyene macrolides.
Fungal infections are increasing rapidly worldwide and pose a growing threat to human health, particularly for older people and those with weakened immune systems. In recent years, dangerous fungi such as Candida auris have spread globally and developed resistance to existing drugs, making these infections difficult to treat and associated with high mortality. At the same time, fungal diseases cause major problems in agriculture and threaten food production. Despite this, only a limited number of effective antifungal drugs are available.
The project focuses on polyene macrolides, naturally occurring antifungal compounds that remain among the most effective treatments and are often used as a last resort. However, their use is limited because they have poor solubility and low bioavailability and can damage healthy human cells, causing serious side effects. At the same time, their precise effects on fungal cell membranes are not yet fully understood.
In this interdisciplinary project, we will develop and synthesise new polyene compounds with improved solubility and greater selectivity for fungal cells. Their effects and mechanisms of action will be studied in model membranes and living yeast cells to better understand how they attack fungi without harming human cells. The project combines organic synthesis, membrane biophysics and microbiology with the aim of developing safer and more effective treatments for resistant fungal infections.

Lars Grøntved, Department of Biochemistry and Molecular Biology. DKK 3,669,120 for the project Defining transcriptional repressor mechanisms regulating zonated gene expression in the liver lobule.
Liver cells perform different metabolic functions depending on where they are located in the liver, a phenomenon known as liver zonation. This spatial division of labour is associated with marked differences in gene expression and is significantly disrupted in a range of liver diseases. At the level of gene regulation, however, we still do not understand how these specialised cell functions are maintained or how they become disrupted during disease.
This project will investigate how the organisation of DNA within liver cells, and thus the regulation of gene expression, controls these location-dependent functions in both healthy liver tissue and metabolic liver disease. By developing new methods for labelling zone-specific liver cell populations in rodents and combining these with advanced genomic technologies, the project will investigate how the protein TBX3 and related regulatory proteins contribute to both zonation-related and disease-related differences.
In the longer term, this knowledge could contribute to improved laboratory models of the liver and support the development of new treatments for metabolic liver disease.

Carsten Uhd Nielsen, Department of Physics, Chemistry and Pharmacy. DKK 3,670,560 for the project Beyond Single-Target Inhibition: Pan-inhibitors for LeuT-Fold Amino Acid Transporters in Cancer.
In this project, we will investigate membrane transporters in cancer cells and how they can be exploited to slow cancer cell growth. Cancer cells often upregulate a range of transporters both to protect themselves and to meet their increased demand for nutrients. One key molecule in this context is glutamine, an amino acid that is essential for rapid cell growth. Increased uptake of glutamine by cancer cells is caused by the upregulation of several amino acid transporters.
The aim of the project is to develop molecules that can inhibit the function of these transporters. Unlike traditional approaches, which typically focus on a single transporter, we propose a new strategy: developing compounds that block several types of transporter simultaneously. The basic idea is simple: if several transporters share the same substrate, glutamine, it should also be possible to identify inhibitors that act on a group of transporters.
We will therefore draw on recent advances in structural knowledge of amino acid transporters, access to large ‘make-on-demand’ chemical libraries, advanced AI-based search strategies and in vitro cell-based methods. These tools will enable us to investigate how new multitarget inhibitors affect cancer cell growth by depriving the cells of the essential amino acid glutamine. The project has the potential to change the way amino acid transporters are targeted and to provide a basis for new drug candidates that could benefit patients.

Here is DFFs own news story on the 2026 DFF1 grants (in Danish).