From medicines from snake venom to supercrops and plastic-eating enzymes. Nine researchers from Leiden University will receive Open Competition XS grands from the Dutch Research Council (NWO).
The Open Competition XS grants of a maximum of € 50,000 are intended to support promising ideas and to facilitate innovative and more speculative initiatives. 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.
Ramon Arens (Leiden University Medical Center)
As part of the immune system, killer T cells play a key role in eliminating virus-infected and cancerous cells. However, repeated infections throughout life lead to the buildup of terminally-differentiated T cells (TEMRA), which have reduced capacity to respond to new immune challenges. This reduced responsiveness may contribute to the increased risk of cancer with age. In this project, we will investigate how cellular metabolism regulates TEMRA function and explore strategies to metabolically reprogram these cells in order to boost their ability to fight cancer.
Marta Artola Perez de Azanza (Leiden Institute of Chemistry)
The COVID-19 pandemic has highlighted the urgent need for new antiviral treatments. One promising novel approach is targeting complex RNA structures, which play key roles in viruses like SARS-CoV-2. However, finding molecules that bind to RNA is very challenging because RNA is flexible and lacks stable binding sites. Current methods to find these molecules are slow or require a lot of effort. This research introduces a faster, easier way to screen for molecules that target specific SARS-CoV-2 RNA structures. The goal is to discover new molecules that could lead to innovative antiviral therapies.
Jasper Demandt
Cardiovascular diseases are the worldwide leading cause of death, yet development of novel medication in the cardiovascular field is scarce and many new medicines are based on known drugs. At the same time, nature offers a liquid goldmine of bioactive compounds in the form of snake venom: mixtures of hundreds of proteins evolved over millions of years to perfectly target a plethora of physiological processes. Demandt will develop an innovative high-throughput platform to fractionate snake venoms and systematically screen their individual components for potential therapeutic activity in cardiovascular disease.
Stephan Hacker (Leiden Institute for Chemistry)
Antibiotic-resistant bacterial infections are among the most urgent threats to human health. Especially, Gram-negative bacteria, for which no new antibiotic class has been discovered in more than 50 years, pose an enormous challenge for antibiotic development due to their almost impenetrable outer shell. Here, the researchers will efficiently synthesise and analyse compounds that are uniquely optimised for both uptake into Gram-negative bacteria as well as antibacterial activity. In this way, they will ideally develop new starting points for future antibiotics and, in any case, obtain novel insights into the feasibility of this strategy to enable uptake into various Gram-negative bacteria.
Dane Marijan (Leiden Institute for Chemistry)
Neurodegenerative diseases are devastating conditions characterised by proteins aggregating into toxic, damage-resistant amyloid fibers, which pose an exceptional challenge to neuronal cells. Recent findings have demonstrated a mechanism by which chaperone proteins can disassemble these fibers. However, it is not known if this occurs inside living cells, since the crowded environment inside them makes it extremely difficult to unambiguously observe this mechanism with sufficient resolution. This project will develop an accessible experimental approach that will allow researchers to visualise the mechanism of amyloid processing within complex cellular environments in single-molecule detail.
Paula Niewold (Leiden University Medical Center)
Tuberculosis is the deadliest infectious disease globally and results in 10 million new infection cases annually. Our incomplete understanding of immune responses protecting against this lung disease has hampered the development of novel vaccines. Recent work administering vaccines in the lung instead of the skin induced B cell responses and greatly improved protection. The researchers therefore hypothesise that antibody-producing B cells contribute to protection mediated by lung vaccination and that targeting these cells directly can further improve vaccine efficacy. This project will study how B cells are impacted by lung administration of tuberculosis vaccines.
Marcel Tijsterman (Leiden University Medical Center)
Global food security is increasingly threatened by climate change and environmental stresses like drought and soil salinisation. To meet growing food demands sustainably, innovative solutions are essential. This project explores a newly discovered genetic phenomenon: plants with a mutation in the TONSOKU gene accumulate tandem duplications - extra DNA segments that can boost gene activity. These changes may enhance valuable traits such as yield or stress tolerance. By analysing these duplications and creating an open-access mutant collection, this project will provide a novel tool for plant researchers to accelerate the development of resilient crops, and thus contributing to sustainable global food production.
Henri Versteeg (Leiden University Medical Center)
Pulmonary embolism patients suffer from blood clots in their lungs, and these blood clots often persist despite therapy. These blood clots often contain blood vessel cells that induce scars in blood clots. The researchers presume that these 'scar cells' prevent these blood clots from being broken down. In this project they will use an unprecedented approach and unique infrastructure, comparing gene expression and cellular behaviour of these scar-forming cells with cells from pulmonary emboli that do not show scars. Their results will show for the first time if and how these scar cells acquire features to prevent dissolution of pulmonary clots.
Han de Winde (Institute of Biology Leiden)
This project aims to unravel and engineer a complete enzymatic degradation pathway for polyethylene (PE), the world's most produced yet most recalcitrant plastic. While some PE-degrading microbes and microbial communities have been identified, no specific enzymes have been confirmed. Using advanced computational protein prediction and biochemical identification, the researchers will identify and validate enzymes involved in the stepwise breakdown of PE. This innovating approach enables the selection of novel enzymes from diverse microoorganisms to design an efficient, engineered pathway. The outcome will lay the molecular foundation for enzymatic PE recycling, advancing a more sustainable circular carbon economy.
