The Open Competition Domain Science – XS grants are intended to support promising ideas and to facilitate innovative and more speculative initiatives within the seven Domain Science disciplines. The proposed research is ground-breaking and high-risk. What counts is that all results, be they positive or negative, must contribute to the advancement of science. The researchers receive a maximum of € 50,000.
The assigned VU applications (in alphabetical order of the applicant):
Assistant professor of bioanalytical chemistry Melissa Baerenfaenger for her research How does Parkinson’s disease begin? A Molecular Look at the Origin of Protein Aggregation.
Parkinson’s disease is a neurological disorder initiated by the pathogenic aggregation of the protein α-synuclein in the brain. Baerenfaenger investigates how aggregation begins; a poorly understood but crucial step. She uses ion mobility mass spectrometry, a powerful technique that provides structural insight into early stages of α-synuclein aggregate formation. Unlike previous studies that use simplified proteins, Baerenfaenger focuses on native protein modifications known to occur in the human brain. Comparing modified and unmodified α-synuclein will reveal how these modifications affect early aggregation to uncover how Parkinson’s disease starts; so we can take the first steps toward stopping it.
Biophysicist Volha Chukhutsina for her researchSF-TA: Towards scattering-free measurements in transient absorption spectroscopy.
Optical spectroscopy has been indispensable to the progress of photobiology and photophysics. Its most powerful implementation is called transient absorption spectroscopy (TA). TA is a technique for studying ultrafast photophysical and photochemical processes. However, TA measurements are rarely performed on highly scattering samples such as plant leaves, intact algae or protein crystals. As a result, many questions related to photobiology and photosynthesis that can only be studied in vivo remain largely unaddressed. The aim of this project is to develop a scatter-free TA setup (SF-TA) that is highly suitable for measurements on the most relevant photosynthetic and photobiological samples.
Professor of Climate Extremes and Societal Risks Dim Coumou for his research Are Tropical Drivers Behind Recent Changes in the European Jetstream?
Recent changes in the European jetstream have led to more frequent droughts in southern Europe and heavy rainfall in the north during winter. These trends are not captured by state-of-the-art climate models, posing a critical challenge for accurately assessing future extreme weather risks. Coumou explores whether shifts in tropical climate patterns are driving these changes in the jetstream. Using new global datasets and advanced analysis techniques, he will examine how tropical variability influences European weather extremes that current models fail to capture. His findings can guide climate model development and thereby inform more effective adaptation strategies to extreme weather.
Neuroscientist Janina Kupke for her research EPI-SYNAPSE: Epigenetic regulation of the synaptic code underlying memory persistence.
How are memories stably stored in the brain despite constant protein turnover? Kupke investigates whether DNA methylation - a lasting epigenetic mark - regulates the synaptic protein landscape of memory-storing engram neurons. Using targeted manipulation of DNA methylation, combined with synapse-specific proteomics, she aims to identify molecular signatures underlying memory persistence. This high-risk/high-gain approach will generate the first proteomic map of epigenetically regulated engram synapses, offering insights into memory stability and paving the way for future studies on disorders like Alzheimer’s and PTSD.
David Poole for his research Rings with Wings, Modified Cyclodextrins for Non-covalent Derivatization in Mass Spectrometry Imaging of Lipids.
Non-polar lipids like cholesterol play critical roles in disease but are notoriously difficult to detect with mass spectrometry imaging (MSI) due to poor ionization. Poole introduces a novel, non-covalent derivatization approach using ionizable cyclodextrins (ICDs) to selectively enhance detection of these elusive lipids. Unlike conventional methods, ICDs minimize complex sample preparation and feature useful size-selectivity in binding. By enabling fast, high-resolution visualization of lipid distributions in biological samples, this strategy would transform chemical imaging and unlock new investigatory tools into the role of lipids in metabolic, cardiovascular, and neurodegenerative diseases—significantly expanding the reach of MSI in biomedical research.
Victor van Santen from Academic Centre for Dentistry Amsterdam for his research The Missing Piece of The Puzzle in Developing T-cell Treatments for Solid Tumors.
Recently, it has been shown that genetically engineering a patients’ immune cells can cure several blood cancers. However, this therapy does not work for solid tumors (non-blood tumors). Accurate cell models to investigate how immune cells can also kill solid tumors are sorely lacking. In the human body, solid tumors experience compression, which can prevent immune cells from killing cancer cells. Therefore, Van Santen aims to develop a tumor model that includes compression. The proposed cell model holds the potential to save lives by revolutionizing treatments for solid tumors with genetically engineered immune cells, similarly to blood tumors.
Assistant professor Medicinal Chemistry Henry Vischer for his research LIGHT-2-FIGHT: optical ON/OFF switches to fight cancer.
Optical control of biological processes is one of the holy grails in biology and medicine as it is non-invasive and can be applied very locally. Vischer aims to develop ON/OFF switchable molecules to block the chemokine receptor ACKR3 to allow very local inhibition of tumour cells and avoid side effects via this protein elsewhere in the body. These molecules will be synthesised and studied for their ability to be switched on/off by light. Ultimately, suitable tools will be studied for the light-dependent blockade of ACKR3 and (in the future) in a mouse model of ACKR3-dependent tumour growth.