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 assigned VU applications (in alphabetical order of the applicant):
Assistant professor of bioanalytical chemistry Melissa Baerenfaenger for her research GlycoTrace: Overcoming Biomarker Limitations with Glycosylation Traces of Brain-derived Proteins.
Losing track of conversations or feeling confused in familiar places can be frightening, both for those affected and their families. Our research aims to find novel biomarkers for early detection of Alzheimer’s disease to get patients the right support as soon as possible. To do this, we explore a new type of biomarker: sugar molecules, so-called glycans, that attach to brain-derived proteins and their changes during disease. By analyzing these glycan patterns using mass spectrometry, we aim to identify molecular “traces” of Alzheimer’s disease. These findings guide the way to reliable tests for early diagnosis of Alzheimer’s disease.
Professor of Medical Microbiology and Infection Prevention Wilbert Bitter for his research Teaching Old Drugs New Tricks: An in vivo Repurposing Drug Screen to Fast-Track New Tuberculosis Cures.
Tuberculosis remains one of the world’s deadliest infectious diseases, and current treatments are slow (typically months), toxic, and increasingly ineffective due to rising multidrug resistance. This project takes a new approach to find better therapies by testing already safety-proven medicines directly in a living infection model. Using tiny zebrafish embryos infected with tuberculosis-like bacteria, we can rapidly identify available drugs that are effective inside the body, not just in a petri dish. This whole-organism screen will reveal promising treatments that traditional methods overlook, offering a faster and safer path toward new tuberculosis therapies.
Dennis Botman for his research Lightning up glycolytic NAD+ oscillations to understand diabetes.
Diabetes mellitus affects ~600 million adults worldwide and although symptoms can be diminished, a cure is not present, decreasing quality of life. Preventing or reversing the disease requires understanding how pancreatic β-cells regulate insulin secretion. Glycolytic oscillations, critical for insulin release, are traditionally measured by NAD⁺ autofluorescence in extracts or pooled cultures but cannot be done in living single cells due to cytotoxic light exposure. To advance, robust, pH-stable NAD⁺ sensors are needed to measure glycolytic dynamics in individual β-cells. We propose developing such sensors via an optimized high-throughput yeast screening pipeline, enabling detailed single-cell studies with broad biomedical implications.
Bioanalytical chemist Ariadni Geballa-Koukoula for her research BlaDeS-PD: Blade Spray Detection of a-Synuclein Oligomers in Parkinson's Disease.
Parkinson's disease affects millions worldwide, but diagnosis comes too late and after most brain cells are already damaged. This project develops a new detection method combining two technologies: specialized antibodies that recognize early disease markers, and a rapid surface-based mass spectrometry analysis technique. Unlike current methods requiring hours of preparation, our approach delivers results in minutes while preserving the natural structure of disease markers. This proof-of-concept study will demonstrate whether this innovative combination can detect Parkinson's markers at very low concentrations. Success would open doors to earlier diagnosis and better treatment outcomes.
Shweta Godbole for her research Accelerating brain cancer diagnosis with Proteogenomic Analysis of circulating extracellular vesicles.
Patients suspected of brain cancer often present with headaches, speech or vision changes, or hallucinations. Both gliomas and primary central nervous system (CNS) lymphomas (PCNSLs) cause these symptoms but originate from completely different cell types (neuronal- and immune origin respectively) and require distinct treatment. PCNSL diagnosis can take 21–47 days, and if untreated, survival averages just 1.5 months. Faster, less invasive diagnostics are thus urgently needed. Here we will test the hypothesis that ‘proteogenomic’ profiling of tumor-derived extracellular vesicles present in patient blood can, in the future, replace current invasive approaches to distinguish brain tumor types.
Experimental physical chemist Giulia Lo Gerfo Morganti for her research LiveTrack – Towards direct tracking of energy transport in biological systems.
Understanding transport phenomena is fundamental across physics, chemistry, and biology. In photosynthetic systems, a long-standing question - how far and how fast energy is transported - is crucial for improving efficiency, currently below 1%. Answering this requires nanometer spatial and picosecond temporal resolution at low illumination, necessary to avoid photodamage - a combination conventional microscopy cannot achieve. This project will develop an advanced microscopy setup to resolve energy transport under physiologically relevant illumination, providing the first direct measurements in native biological materials and establishing a methodology broadly applicable to other photofragile or complex systems.
Physicist Ermes Peci for his research Chirality-driven separation of light for next-generation optical chips.
Modern silicon-based electronics are approaching their limits in speed and energy efficiency, creating a need for new ways to process information. Using light instead of electrical currents offers a promising alternative. This project explores a new type of light-based chip built around an ultra-thin material, molybdenum disulfide, only a few atoms thick. Information in this material can be encoded in distinct electronic "valleys." By combining molybdenum disulfide with specially designed optical nanostructures, the chip can separate and guide light originating from different valleys into distinct outputs, opening a path toward faster and more energy-efficient information technologies.
Physicist Susan Rigter for her research Movement to Power: Metal-Free Perovskites for Self-Powered Health Devices.
Imagine self-powered personal health devices such as pacemakers, requiring no battery charging or replacement, removing the need for risky replacement surgeries. This proposal explores a revolutionary alternative: using the body’s movement to power health devices, via piezoelectric materials. We propose to use metal-free perovskites. These are soft, flexible, sustainable materials with promising piezoelectric properties. By mixing components in their crystal structure, we aim to tune the piezoelectric properties for optimal energy conversion at human movement frequencies. Through mechanochemical synthesis and intricate characterization, we’ll deliver a proof of concept that could transform healthcare, enabling self-powered implants and wearables.
Chemist Johannes Schneider for his research From Serpents to Signals: Discovering New GPCR Ligands from Snake Venoms.
Schneider explores new molecules that can affect GPCRs, key proteins in the body and drug development. Snake venoms, rich in powerful but mostly unknown peptides, will be broken down and tested on human cells to find components that activate or block these receptors. The result will be new peptide ligands and a faster method to discover similar natural compounds.
Alexander Speer for his research Lethal Logistics: Exploiting the Iron “Mail Box” of Tuberculosis for Targeted Nanotech Sabotage.
Iron is the fuel of life, and the tuberculosis bacterium (Mtb) is addicted to it. To survive, Mtb relies on a strict supply chain: sending out molecular scavengers (siderophores) to fetch iron through a narrow "mail box" in its armor. We propose to hijack this logistics system using nanotechnology. By attaching the scavengers to nanobeads, we deploy two sabotage strategies: "Poisoned Parcels" (small, toxic beads that sneak inside to kill) and the "Jammed Mail Box" (oversized beads that permanently plug the opening). This strategy of "Lethal Logistics" turns the bacterium’s essential hunger for iron into its fatal weakness.
Bioinformatician Olga Tsoy for her research RareNetworks - Unlocking Rare Diseases with Imbalance-Aware scRNA-Seq Gene Regulatory Network.
Over 400 million people worldwide suffer from rare diseases. Each disease affects a small population, and it results in a critical analytical challenge - data imbalance: typically, 5-10 samples versus hundreds of healthy controls. Single-cell RNA-Seq, a promising source for identifying rare disease-associated genes, presents additional challenges of high dimensionality and the natural variation between cells.Our high-risk/high-gain RareNetworks project will transform severely imbalanced data into actionable information: which genes malfunction and why. We will challenge our method at extreme ratios of 1:50 or higher, determine its reliability limits, and deliver software for therapeutic target discovery.
Assistant professor in Medicinal Chemistry Henry Vischer for his research SpotLIGHT on Tumors: Light-Controlled Cancer Drugs in Action.
Optical control of biochemical processes is one of the emerging promises in biology and medicine as light is non-invasive and can be applied with high spatiotemporal precision. In this XS-proposal we aim the develop light-switchable ‘ON/OFF’ molecules to activate the histamine H4 receptor (H4R) very locally in cancers to stop cell growth, while avoiding side-effects via this protein elsewhere in the body. These molecules will be generated and characterized for ON/OFF-switching upon illumination. Suitable molecules will be tested for light-dependent stimulation of H4R-mediated antitumor activity on cells and (in the future) in mouse cancer models.
The researchers receive a maximum of € 50,000.