23 Utrecht-based researchers receive Veni grant

Twenty-three promising, young Utrecht researchers will receive a Veni grant of up to 280,000 euros from the Dutch Research Council (DRC). This will allow them to further develop their own research ideas over the next three years. Five Veni grants will go to the Faculty of Science, one to Veterinary Medicine, two to Humanities, four to Geosciences, two to Social and Behavioural Sciences, six to the UMC Utrecht,  two to the Prinses Máxima Centre and one to the Hubrecht Institute. Below is a summary of all research projects.

Bringing molecules together: Photoredox chemistry squeezed into small pores

This research proposal of Bettina Baumgartner aims to make chemical reactions more energy efficient. The goal is to convert CO₂ and CH₄ into basic chemicals using only sunlight. It is a translation of biological processes that help to convert molecules, such as photosynthesis. Experimental setups based on spectroscopy will be developed to study photoreactions on nanosecond timescales. This will lead to new insights, and eventually help to improve the efficiency of the photoreactions. The researcher will use small, confined spaces in materials called metal-organic frameworks (MOFs).

Cell Surface RNAs as Therapeutic Targets

“Catch me if you can!”, says cell-surface ribonucleic acid (RNA). RNA is an important biomolecule with many functions in the cell. Recent research suggests the presence of these molecules on the outer surface of living cells. These cell-surface localised RNAs (csRNAs) are challenging molecules to study, because of the lack of tools to detect and identify them. In this research project, Jack Li will develop technology to study and understand the functions of csRNAs, and demonstrate the therapeutic potential of targeting them.

Inside the matrix: Modelling cell-matrix mechanics to predict cell migration modes in cancer metastasis

Cancer is a significant healthcare challenge. Some cancers are benign and can be cured by surgically removing the tumour. Others are malign, meaning that the cancer cells move away from the original tumour to make new tumours elsewhere in the body, otherwise known as metastases. Once a tumour has spread, the chances of successful treatment worsen. Erika Tsingos will develop better computer models of how cells move inside tissues of the body. Ultimately, the researchers want to understand why some cancer cells sit still while others move, and how we can artificially bring them to a halt.

Make it better, not worse: Using formal methods to safely adopt memory-safe languages

Certain types of programming mistakes can have a tremendous impact on software systems. A single mistake is often sufficient to make the entire system vulnerable to cyberattacks. A new generation of so-called ‘memory-safe’ programming languages eliminates these vulnerabilities from the software. However, when developers gradually migrate their systems to these languages, they can accidentally introduce new vulnerabilities in the software and make existing vulnerabilities more dangerous. This leaves the system even more vulnerable than before the migration. With this project, Marco Vassena aims to use mathematical logic to enable developers to migrate their systems so that they will become safe.

How has ageing impacted the evolution of cooperation during two major evolutionary transitions?

Social animals are known to age much slower than non-social animals. For example, naked mole rats are small rodents live in social colonies and hardly suffer from ageing. The question is whether these social species are more likely to become long-lived, or whether long-lived species are more likely to become social. Analogously to how individuals cooperate to form breeding colonies in social species, at some point individual cells started cooperating to form multicellular organisms, like humans. In this project, the researchers will investigate whether the evolution of cellular cooperation changed the ageing rates of cells.

NASH-in-a-dish: Identifying targetable metabolite crosstalk for NASH treatment

Non-alcoholic steatohepatitis (NASH) is an inflammatory reaction of the liver in response to non-alcoholic fatty liver disease. NASH is becoming the leading cause of liver failure and liver cancers, but there is no effective treatment. Aberrant metabolic crosstalk in liver drives NASH progression, but till now it cannot be studied directly in liver tissues. In this proposal, Jung-Chin Chang will develop a novel co-culture system, “NASH-in-a-dish”, to model NASH in a culture dish. By studying the metabolic crosstalk of different liver cells, he aims to identify disease-causing metabolites that can be targeted to treat NASH in the future.

Refugee rights are human rights

Around the world, there are tens of millions of refugees. The issue of how to respond to refugee flows has been on the international agenda since the twentieth century. Often, responses have been limited to charity, if not hostility. However, the project of Bastiaan Bouwman shows,  how an international network advocated for the rights of refugees in the second half of the twentieth century. By working for the recognition of these rights as human rights, they hoped to achieve change. Based on international archival research, the project explains both their success and their limitations.

A just climate transition

Jeroen Hopster's research is about a just climate transition. That transition is necessary, but not everyone benefits immediately: for some, the future of their business is at stake, others will have to adapt their lifestyle. Under what circumstances is some form of compensation appropriate in this, from a moral point of view? Over the next three years, he is working on an ethical theory of just transitions. This grant will enable him to lay the foundations for that, and to strengthen research on climate ethics at Utrecht University.

Deltas as a record of ancient hydrological conditions on Mars

Deltas are important landforms for resolving past environments, as their shape and deposits are testimony to past fluvial activity. Lisanne Braat will use physical experiments, numerical modelling, and orbital data to investigate and reconstruct deltas on Mars to learn how their shape and deposits relate to water and sediment supply from the hinterland. "My research will constrain the amount, duration, and extent of liquid water at the surface of Mars and will have implications for research on life and climate on Mars and for future space exploration. I am honored to have the opportunity to apply my knowledge of deltas on Earth to Mars.”

Witnessing tectonic catastrophe—What causes the violent birth of subduction plate boundaries?

Subduction zones drive global plate tectonics, yet their birth is mysterious. These zones are where all the action happens - rocks bend and break as they grind and flow past each other, sometimes releasing pent up stress as earthquakes. They also control geochemical cycles, perhaps even allowing life as we know it to flourish, but we do not understand the physical processes that create these highly localized zones. After slow initial convergence, subduction zones initiate with a sudden, catastrophic collapse of a plate into the mantle, but the cause of collapse is unknown. Research of Alissa Kotowski shows that rocks in the syn-collapse plate contact are colder than they were pre-collapse; thus, she hypothesizes that mineral changes resulting from cooling weaken flow behaviour. She will test this with state-of-the-art 2D-and-3D structural imaging of rocks recording various stages of subduction lifetimes. If correct, this research may explain the onset of self-sustained plate recycling and will impact understanding of the start of plate tectonics.

GREENPEAKS: Mountain greening and its impacts on water supply from the mountains

Mountain regions are an important source of water for downstream areas. The downstream water availability is strongly influenced by the amount of mountain vegetation and its impacts on the mountain water balance.Philip Kraaijenbrink's project investigates the extent to which climate change affects vegetation change in mountain regions and assesses its potential implications for the water supply from the mountains.

Retro innovation: combining the old and the new for sustainability

Sustainable innovation is often only associated with breakthrough technologies. Toon Meelen’s project shows that sustainable innovation can also consist of combinations of old, existing and new practices and technologies. For night trains, zeppelins and hitchhiking, Toon Meelen will investigate strategies by which organisations revive lost ways of transport with modern technologies and new meanings.

Understanding the world: better models for social and behavioral phenomena

Scientific research uses statistical models to describe and understand real-world social and behavioral phenomena. As more data is being collected, these statistical models become larger and more complex. Sara van Erp will develop novel methods so that researchers can use these increasingly large and complicated statistical models to better understand the world.

Tailor self-regulated learning support

As higher education becomes increasingly digitalized, blended learning is now commonplace. This places even greater demands on students’ self-regulated learning, which poses difficulties for many students. The project of Jacqueline Wong aims to personalize and tailor self-regulated learning support to meet individual needs when working on different learning tasks. This is a major challenge as it requires integrating data obtained during both digital and face-to-face course components. Therefore, Wong will use a multidisciplinary approach to investigate ways to measure and support self-regulated learning in blended learning environments.

Stimulating the childhood immune system: strengthening the relationship between young immune cells

Intimate interaction of T cells of the immune system with (antibody-producing) B cells is essential for the generation of effective and long-lived protection against pathogens. This interaction is less effective in children. Theo van den Broek discovered that very young T-cells are more functionally versatile and responsive than previously thought and respond to different triggers than adult T-cells. In this project, he will investigate in detail how young T cells instruct antibody responses by B cells. A better understanding of the T:B-cell interaction may lead to increased effectiveness of childhood vaccinations.

Finding the way in – Identifying entry and cargo release pathways of extracellular vesicles

Cells in the body communicate with each other by sending and receiving tiny information packages, called extracellular vesicles (EVs). EVs play a role in various diseases, such as cancer, but can also be used to deliver medicine to diseased cells. We don’t fully understand how cells receive and unpack EVs. This is key in understanding how communication via EVs works. Tom Driedonks will investigate which proteins in and around cells play a role in the receiving and unpacking of EVs. We can use this information to block disease-related EV uptake, and to more effectively deliver medicine into diseased cells.

New evidence in the search for effective ALS treatments: a patient-focused drug development strategy

Debilitating neurogenerative diseases, such as amyotrophic lateral sclerosis (ALS), are characterized by highly variable symptoms, complicating the assessment of new treatments, and delaying the development of effective therapy. Patients are thereby exposed to potentially ineffective and harmful drugs, or beneficial treatments are missed in clinical trials.

Ruben van Eijk will develop novel statistical methodology for clinical trials to simultaneously encompass the totality of symptoms, patient preferences, prognosis, and clinical relevance. This research will redefine treatment benefit for patients, enabling more efficient, impactful and patient-focused drug development to improve patient outcomes.
 

Uncovering the patho-molecular aetiology of the novel XPO1-related neuro-developmental disorder

Inborn brain malformations often originate from heritable defects. Tracking these defects in the DNA can gain valuable insights into how the development of our most complex organ, the brain, is orchestrated. Defects in the XPO1 gene have recently been identified as a novel cause for brain anomalies. In this project, Richard van Jaarsveld will recreate these defects in the lab to study the impact on brain development. The expected results will forward our understanding of brain development, which could contribute to the prevention and treatment of inborn brain malformations.

Visualizing the needs of osteoarthritis patients: learning from exceptional cases of cartilage repair

Osteoarthritis is a highly prevalent disease with high impact on patients, healthcare, and society, characterized by degeneration of joint cartilage. Successful treatments should therefore induce cartilage regeneration, but most investigational approaches thus far have failed. However, there are patients who show cartilage repair, after specific treatment or even spontaneously. In this project, Mylène Jansen will use state-of-the-art image analysis techniques, combining data and images from existing cohorts with patients showing this unique repair activity, to identify conventional and novel joint characteristics that may be essential to induce repair in osteoarthritic joints. This will directly provide novel tools for stratified treatment modalities.

SMA BABIES – Systematische Multimodale Analyse naar BiomArkers en Bulbaire functie In (pre)symptomatischE SMA

SMA is a hereditary severe childhood-onset motor neuron disorder and the first-ever disorder effectively treated by gene-targeting therapies. They dramatically improve disease course, especially in patients early-diagnosed in the newborn screening program. Pre-symptomatic treatment is key, but the cure is incomplete, and we are in desperate need of biomarkers that predict disease severity and prognosis at time of diagnosis. The high societal impact due to extreme costs of these therapies also demands treatment optimization. Renske Wadman's innovative multi-modal approach combines clinical scores, genetic, protein, ultrasound and EMG-studies, to evaluate and predict disease severity, variability, and treatment efficacy in early-diagnosed babies with SMA.

Dissecting the carcinogenic potential of stem cell differentiation by single-cell whole genome sequencing

Differentiation of stem cells into specialized cells is accompanied by large-scale biological changes in these cells. In this study, Sjors Middelkamp will use new methods to determine how these changes in blood stem cells can cause DNA modifications in these cells. He will compare the profiles of the DNA changes in healthy blood cells with DNA profiles in leukemic cells. In this way, he will determine how DNA changes that arise during stem cell differentiation can contribute to the development of leukaemia. This research will yield new insights in the biological processes that play a role in cancer development.

Characterizing early life hematopoiesis: tracing the first steps towards malignancy

Hematopoietic stem cells are believed to play a crucial role in the generation of all blood cells throughout life. However, the exact mechanism of blood production remains poorly understood, particularly when it comes to studying the process in humans. In this project, Inge van der Werf aims to fill this gap in knowledge by using naturally occurring DNA mutations to recognize and trace hematopoietic cells responsible for blood production in early life. This cutting-edge approach will provide unique and unprecedented insights into the behavior of hematopoietic cells during blood production, which will be crucial to understanding leukemia's biology in future studies.

The difference is night and day: DNA repositioning in the nocturnal retina.

The function and identity of cells are largely determined by which genes are on or off, which is in turn largely regulated by the packaging of DNA and where it is positioned in the nucleus. In all vertebrate cells, inactive genes are positioned at the nuclear periphery. However, this typical organization is inverted in the retinal rod cells of nocturnal mammals, in which active genes now occupy the periphery. Robin van der Weide will study this unconventional genome organization by employing unique single-cell technologies and innovative models to elucidate the evolution of gene regulation. This will aid in developing new gene therapies.