Space for high-risk research in Nijmegen

Six Nijmegen research projects will receive grants within the NWO Open Competition ENW-XS. These ENW (Exact and Natural Sciences) grants are intended to enable promising ideas and innovative and high-risk initiatives. The research is groundbreaking and it is not certain in advance whether the intended objective will be achieved. What matters is that every result, whether positive or negative, helps science move forward. It is explicitly about curious, adventurous research and being able to explore a promising idea quickly.

The honored projects:

Sweet science: how sugar shapes protein function in cancer
L.A.M. (Lenneke) Cornelissen (Radboud university medical center )

Glycosylation, the attachment of sugars to proteins, is a common protein modification that is generally required for proper protein function. Sugar production and glucose metabolism are closely linked because they both require glucose molecules. Whether physiologically low glucose levels, such as in a tumor setting, can alter the sugar profile of proteins and thus egg white function, has not been investigated. Here, we will investigate the influence of glucose molecules on the sugar profiles of (tumor) proteins and thus protein functionality. The study will contribute to our knowledge of how protein functions are regulated by their sugar layer.

Nanowelding meets biology: cell-compatible 3D metal welding by light
M. (Mani) Diba (Radboud university medical center )

Metallic structures are fundamental to our daily lives, from constructing durable buildings to facilitating electrical conductivity in devices. Beyond the types of metallic materials we use, the techniques we employ to join them together are crucial for their effective use and functionality. As many cells in our body are electrically active, the integration of electroconductive metallic structures with cells is becoming increasingly vital for cell biology and biomedicine. However, traditional metal-joining techniques are cell-destructive. This project will overcome this challenge by harnessing the potential of light-driven nanowelding to enable new frontiers for the integration of metallic structures with biological systems.

Prostate cancer’s SECRETome: decoding molecular whispering
M.V. (Victoria) Luna Velez (Radboud university medical center )

Therapieresistant prostate cancer is a fatal disease with a life expectancy of 2 to 3 years. Intracellular communication between tumor cells and between tumor cells and their environment are a source of potential biomarkers and therapeutic targets. It is impossible to study these signals in vivo. In this project, we therefore propose to apply a click chemistry-based method to patient-derived 3D in vitro tissue cultures (tumoroids and explants) to fully map intercellular communication traffic in therapy-resistant prostate cancer for the first time. This approach offers numerous research opportunities with biological and clinical relevance.

Does cellular stress promote Parkinson’s disease? Studying aggregation of α-synuclein in stress granules with genetically encoded minimal labels PES-A
W.P. (Wojciech) Lipinski (Radboud University Nijmegen/ Radboud university medical center )

Parkinson's disease is one of the most common neurodegenerative diseases caused by the aggregation of the protein α-synuclein. There is evidence that liquid droplets that occur naturally or during stress in the cell accelerate protein aggregation. However, there is not yet a method to map this process and test potential new therapies targeting the droplets. We are developing a new method to study the unexplored protein aggregation mechanisms in the cell live and in a non-invasive manner. Specifically, we are investigating whether prolonged or repetitive stress could increase the risk of Parkinson's.

Decelerating Antibiotic Resistance
W.A. (Willem) Velema (Radboud University Nijmegen)

Antibiotic resistance is increasingly becoming a threat to human health. Traditional attempts to stop resistance have focused on expanding our arsenal of effective antibiotics, with limited success. Here we propose to explore an unconventional approach to counter resistance by preventing bacteria from developing resistance in the first place. We will target the main regulator responsible for acquiring resistance in bacteria with so-called antisense agents. Ultimately, we hope this approach can be applied to slow antibiotic resistance and address the resistance crisis.

Photoelectron Vortex Dichroism: studying chiral molecules, with a twist!
C. (Christopher) Sparling (Radboud University Nijmegen)

Chiral molecules (molecules that do not overlap with their mirror image) are of great importance in biological/medical chemistry. Developing analytical methods with optimal chiral sensitivity is therefore crucial for better characterization of new drugs. Currently, such analyses are performed using spectroscopic techniques based on the inherently weak interaction between circularly polarized light and the chiral sample. Thus, exploiting stronger physical interactions could significantly improve chiral sensitivity. This proposal will explore for the first time the use of rotated light and optical vortices as an innovative, stronger method for detecting molecular chirality.

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