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Nine researchers from Utrecht have received funding in the 25th round of the NWO Open Competition ENW-XS. The grants (of up to 50,000 euros) are intended to enable small-scale, innovative and risky initiatives within the seven ENW disciplines. A total of 2.4 million euros has been distributed. The Utrecht projects cover a wide range of themes, including the use of snake venom for pain relief and protection of kidneys against chemical damage, nanocrystals for energy-efficient AI, new insights into viral spread and the effect of gut bacteria on immunotherapy.

Dr. Silvia Mihăilă (Faculty of Science)

Cracking the code of cellular resilience: learning from cancer how we can protect the kidneys

Chemotherapy is a well-established method for attacking cancer cells, but some tumours develop resistance and manage to survive, making treatment less effective. At the same time, healthy kidney cells are highly vulnerable to these drugs and often suffer lasting damage after treatment. Bioengineer Silvia Mihăilă aims to uncover what cancer cells do to survive chemotherapy, and whether similar protective mechanisms can be triggered in kidney cells. By analyzing gene activity and cell metabolism, her team hopes to identify key processes and test compounds that could shield the kidneys from drug-induced injuries. This research could pave the way for therapies that both improve the effectiveness of cancer treatment and reduce kidney damage.

Dr. Freddy Rabouw (Faculty of Science)

Nanocrystals for neuromorphic computing

New energy-efficient data-processing strategies are necessary, as the electricity demand by artificial intelligence is exploding. Neuromorphic computing is one such strategy, inspired by the human brain. The brain is much more efficient than current computers, because connections between neurons act as memory and processor simultaneously. This project will investigate nanocrystals as a simultaneous memory and processor component for neuromorphic computing. Our calculations show that recently developed nanocrystals [Lee et al., Nature 589, 230–235 (2021)] “remember” how to process input signals, after they were briefly laser illuminated. We will train the nanocrystals to distinguish images of digits 1–9.

Dr. My Anh Truong (Faculty of Science)

Chromosome engineering to unveil aneuploid mysteries in human development

When an embryo develops, it sometimes makes genetic mistakes that lead to a wrong number of chromosomes in a cell. This condition, called aneuploidy, can cause serious issues, including miscarriages and developmental problems. But not all chromosomes are equal: some chromosomes are more often “wrong” than others. And not all cells are equals either. Some cells tolerate aneuploidy better than others. In this project, cell biologist My Anh Truong aims to develop a system to precisely manipulate and monitor aneuploidy in human placental stem cells. This cutting-edge innovation will uncover how specific aneuploidies impact human development, potentially revolutionizing how aneuploidy is diagnosed and managed during pregnancy.

Dr. Xander de Haan (Faculty of Veterinary Medicine) 

Unravelling the role of filamentous influenza A particles in cell-to-cell spread

Influenza A viruses (IAV) cause seasonal epidemics and occasional pandemics of influenza. IAV particles come in two morphologies, the well-studied spherical particles and the often-overlooked filamentous particles. The function of the filamentous particles has not been established, but conservation of this phenotype indicates an important role probably in cell-to-cell spread in the infected host. In this study we will elucidate the relevance of the filamentous particles using live virus-cell imaging in advanced cell culture models. Potentially, this research will lead to novel therapeutic avenues to target this important pathogen. 

Dr. Emma Kasteel (Faculty of Veterinary Medicine)

The bite of relief: exploring the use of snake venom for pain treatment

Millions of people worldwide struggle with chronic pain. Current medications work by trying to block pain nerves. Unfortunately, these medications often do not work well enough, can cause unwanted side effects because they affect other nerve cells and some are highly addictive. Therefore, we need better pain treatments. Interestingly, certain animal toxins (like snake venoms) can target specific nerve cells with great precision. This project explores whether these toxins can be used to reduce pain by calming pain nerves without interfering with other nerve functions. This could lead to safer, more effective pain relief with fewer side effects. 

Dr. Ilia Timpanaro (Faculty of Veterinary Medicine)

Learning and memory in a dish

The ability of our brain to learn and remember is a complex process and we know that exposure to certain chemicals can influence it. However, we don’t yet understand how. Surprisingly, most chemicals have never been tested for their ability to affect learning and memory. This project aims to change that. We will develop an in vitro model that mimics learning and memory using human stem cell-derived neurons and electrical stimulation. This innovative approach will provide a faster, more efficient way to study the impact of chemicals on the brain, without relying on costly and time-consuming animal studies. 

Woutjan Branderhorst (UMC Utrecht)

Better prediction of chemotherapy response of human liver tumors

Woutjan Branderhorst investigates how the effectiveness of chemotherapy in liver tumors can be better predicted. This is important, as treatment response is currently often only visible at a late stage. Using a specialized MRI technique, Woutjan and his colleagues examine the molecule nicotinamide adenine dinucleotide (NAD) in tumor cells. NAD plays a key role in cellular energy metabolism. Previous research in cell cultures suggests that changes in NAD metabolism may be predictive of chemotherapy response. The goal of this project is to improve the MRI method and test it in both patients and lab-grown mini-tumors (organoids). Ultimately, this could enable earlier and more accurate prediction of treatment outcomes and help prevent unnecessary side effects.

Merel van Gogh (UMC Utrecht)

Gut Microbes and Cancer Immunotherapy: Exploring the Impact of ADP-heptose

Immune checkpoint inhibitor (ICI) therapy has become a key treatment by (re)activating the immune system. However, many patients still do not respond effectively. One possible explanation may lie in the gut. The human gut hosts billions of bacteria, which can influence the immune system through the substances they produce. In this proposal, we focus on one such substance: ADP-heptose. This molecule has the potential to activate the immune system, but has been scarcely studied. The aim of this project is to gain a deeper understanding of the role ADP-heptose plays in the response to ICI therapy. Ultimately, this could help improve the effectiveness of this treatment for a broader group of patients.

Dr. Martijn Koppens (UMC Utrecht)

Tracking DNA to solve the unpredictable genetics of mitochondrial disorders

Recent technological advances enable us to repair mutations in DNA, offering the potential for curative therapies for genetic disorders. While most genetic disorders involve nuclear DNA and require repairing just one or two mutations per cell, mitochondrial disorders involve thousands of copies of a mutation per cell. Variations in the fraction of mutant copies complicate predicting prognosis and long-term effects of gene-repair. I will address these challenges by developing a new approach to track mitochondrial mutations in live cells. Monitoring these mutations over time may provide transformative insights in mitochondrial genetics and facilitate development of gene-correction therapies for mitochondrial disorders.