Projects granted by NWO

The projects listed have been published in the newsletter and are the projects granted by NWO that have a connection with Physics of Life.

Please follow the links for full granting information.

2021

Disposing of neurodegenerative diseases: A bivalent molecular approach to degrading intrinsically disordered proteins.
dr. P. Cossar (M), Technische Universiteit Eindhoven
Intrinsically disordered proteins (IDPs) cause neurodegenerative diseases, including Parkinson's and Alzheimer's. Currently, IDPs are considered to be 'undruggable', as drugs cannot stick to these highly flexible and disorganized proteins. This new approach captures the IDP within a protein cage and disposes of the IDP using the cells natural disposal system.

Understanding the molecular origin of collagen’s mechanical failure in osteogenesis imperfecta
dr. G. Giubertoni (V), Universiteit van Amsterdam
Osteogenesis imperfecta is a life-changing, occasionally lethal, disease caused by mutations in the genes encoding collagen, the main building block of all human connective tissues such as bones. I will investigate the molecular origin of this disease and identify the molecular properties determining the success or failure of collagen biomaterials.

Dynamic changes in proteins during embryonic development
dr. S. Stelloo (V), Radboud Universiteit Nijmegen
During early embryogenesis, stem cells develop into various different cell types. The development of different cell types involves changes in both protein expression levels and protein-protein interactions. The researchers will investigate the dynamic changes in protein expression and interaction during the development of embryonic stem cells into more specialized cells.

“Macro”-managing genes
dr. I.K. Mandemaker (V), Hubrecht Institute
All cells in your body contain the same DNA but can specialize into different cell types by turning genes on or off. This is carefully organized by epigenetic processes to prevent disease. This research will show how a newly identified player controls gene activity by placing the biggest epigenetic mark.

2022

DNA-coated vesicles with time-varying adhesion to model cell migration
Dr. Pepijn G. Moerman, TU/eTo grow from a shapeless clump into an intact animal, cells must move by pushing each other out of the way. How strong the cells stick together plays an important role in this process, but it is unknown how exactly changes in their stickiness affect their movement. This research will produce an experimental model of fake cells with controllable stickiness to learn about the role of adhesion changes on cell motion. This insight may eventually help develop drugs that can prevent the spreading of cancer cells by targeting the cells’ stickiness.

Inside the matrix: Modelling cell-matrix mechanics to predict cell migration modes in cancer metastasis
Dr. Eerika Tsingos, UUCancer is a significant healthcare challenge. Some cancers are benign, and can be cured by surgically removing the tumour. Others are malign, meaning that the cancer cells move away from the original tumour to make new tumours elsewhere in the body (metastasis). Once a tumour has spread, the chances of successful treatment worsen. This project will develop better computer models of how cells move inside tissues of the body to understand why some cancer cells sit still while others move, and how we can artificially bring them to a halt.

2023

Understanding how confinement affects the formation of droplets of protein
Dr. I.A.A. Muntz (M), Leiden University
Protein condensates are liquid-like droplets which form in the crowded interior of cells, driving many important processes such as transcription and signalling. Often, cellfree studies of these condensates observe their formation and behaviour in non-confining solutions; however, in these solutions condensate size and distribution generally differs from what is observed in cells. I will for the first time engineer confined environments, such as biopolymer networks, to mimic dense cellular environments, which will allow me to identify how these condensates form in these environments, providing crucial insight into how they behave in living cells.

2024

From design to function: DNA origami nanomachines for protein folding
Eva Bertosin (UU)
DNA nanotechnology is emerging as a powerful technique for building increasingly complex structures with any desired shape, tuneable dynamics, and switchable conformations. I will employ DNA origami to develop nanostructures that mimic the function of the eukaryotic TRiC chaperonin system, an intricately regulated protein complex that folds client proteins. This bottom-up engineering approach allows full control over structural conformations, which cannot be achieved with current protein design methodologies. My project will not only yield deep insights into protein folding and chaperone function but also serve as a stepping stone toward designing nanomachines that carry out novel complex functions.

Cracking the histone code with nanopores
Xiuqi Chen (TUD)
Our DNA contains instructions for life, but these instructions are influenced by special proteins called histones. Like switches, histones can be modified to turn genes on or off. Understanding these modifications is crucial for treating diseases like cancer, but current methods can't decode the effects of the complex histone modifications on our genes. I will develop a groundbreaking novel technology using tiny molecular sensors called nanopores that can simultaneously read both histone modifications and their associated DNA sequences. This new method will help scientists better understand how genes are regulated and potentially lead to more effective treatments for various diseases.

2021

How and why cells split in two?
Dr. A. Chaigne, University of Utrecht
When an animal develops, cells divide to increase the size of the organism. The textbook description of cell division ends with two cells completely separated from each other. However, I discovered that stem cells remain connected via a small tube, called a bridge, filled with proteins. The dismantlement of bridges is crucial to cell fate. Yet, we do not know much about what bridges do and how they are maintained or destroyed. With this project, I will elucidate the molecular mechanisms controlling bridge formation and dismantlement and how the switch between bridge maintenance and destruction controls cell fate transitions.

Do malaria parasites enhance their own transmission?
Dr. F.J.H. Hol, Radboud UMC
Unfortunately, mosquitoes are extremely good at spreading disease by biting people and transmitting parasites. However, we do not know if parasites make mosquitoes even more hungry for blood, and once in our body it is unclear how the parasite finds its way to the bloodstream. By developing new technologies, this research will unravel how interactions between mosquitoes and parasites shape malaria transmission.

Sequence the abnormality
Dr. Miao-Ping Chien, Erasmus MC
Tumors change over time. Abnormalities in chromosomes are a main cause for these progressive changes in the nature and composition of cells that make up a tumor. These changes can lead to therapy resistance in for instance glioblastoma, the deadliest brain cancer. Biophysicists develop a technology to identify rare cancer cells bearing severe chromosomal abnormalities and to study these cells at unprecedented resolution. They investigate the causes and consequences of abnormal chromosomes in glioblastoma and aim to generate information that can lead to improved treatment for glioblastoma.

Visualizing the dynamics of gene regulation
Dr. T.L. Lenstra, Netherlands Cancer Institute
Transcription factors turn on genes at the correct moment in the correct cell type. In this study, we will apply advanced microscopy techniques to visualize individual transcription factor molecules inside cells, while simultaneously measuring when genes are activated. The results will reveal how transient transcription factor binding to DNA regulates the dynamics of gene expression.

The internal dialogue: how our organs communicate via tiny nano-bubbles
Dr. F.J. Verweij, Utrecht University
Almost every cell in our body releases nanometer-sized extracellular vesicles (EV) that are essential for communication with other cells, located nearby or even at distant locations in our body. Yet, owing to their miniscule size, much of how these EVs behave in real life remains enigmatic. Using novel microscopy approaches and transparent fish, we will tap into this communication pathway to better understand the biology of EVs, and how they function in the healthy and diseased gut, in particular during cancer metastasis.

https://www.nwo.nl/en/researchprogrammes/nwo-talent-programme/projects-vidi/vidi-2021

2022

Sense, Decide, Develop: how to maintain accuracy in gene regulation and development
Dr. Marianne S. Bauer, TUDFor organisms to develop well, cell-fate decisions need to be made correctly, and these in turn are based on an accurate sense of the cell’s environment. Researchers will investigate mechanistic processes which contribute to noise, regarding the spatial structure of the genome, on the one hand, and develop information-theoretical and mathematic frameworks to infer optimal network architectures from experimental data on the other. This project is based on experimental collaborations in a series of developing systems, from flies to viruses.

How do cells turn their noise up or down?
Dr. Maike M.K. Hansen, RUCells in our body can be seen as a mini-factory, where there is an assembly line that creates proteins as a final product. The amount of protein each cell makes can vary drastically between even genetically identical cells, this is called noise. Individual steps in this assembly can turn up or down the protein noise. For instance, increasing noise is a phenomenon associated with antibiotic resistance in bacteria or diseases such as HIV and cancer. This project determines how cells can regulate noise, which will improve the understanding of how defects in noise-regulation can result in disease.

A toolbox for epigenetic research
Dr. Danny D. Sahtoe, Hubrecht Institute
Proteins that package and protect our hereditary information (DNA) are often carefully arranged in 3D space within the cell nucleus and also modified by chemical groups. Together, these processes determine which genes are switched “on” and “off”. This proposal describes how synthetic proteins, that will be designed on a computer, will help to unravel how genes are exactly turned “on” and “off”.

https://www.nwo.nl/en/news/97-leading-researchers-receive-vidi-grants

2023

DNActuate: fundamentals of DNA nano-motions for molecular diagnostics
Dr. Sabina Caneva (TUD)
DNA and proteins are fantastic examples of molecular machines. Researchers will develop a new biophysical platform to image and control the dynamics and mechanics of biomolecular processes at the single-molecule level. Combining ultra-flat, biocompatible 2D material surfaces with DNA nanotechnology, they will use fluorescence microscopy techniques to study how molecules move, interact and function. They will use the fundamental knowledge gained to develop new biosensors capable of detecting circulating tumour DNA. This will enable regular monitoring of cancer progression.

How do cells copy the instructions on how to read their DNA?
Dr. Francesca Mattiroli (Hubrecht)
Our DNA is packaged to instruct how, where and when its information is read. Every day our cells make a copy of their DNA and its packaging system before they divide. This ensures that their daughter cells accurately inherit the DNA information and its reading instructions. This is crucial to keep our tissues young and healthy. This research project will study how DNA and its packaging are duplicated, to identify new mechanisms to be targeted for fighting disease and aging.

Read more about Vici and these projects

Next-generation micromaterials for DNA data storage and data editing
Prof. dr. ir. Tom de Greef (TU/e)
DNA holds great promise as a future and sustainable storage medium for archival data. In this project, the researchers will develop smart micromaterials and technologies that will improve the reading of data stored on DNA as well as enable manipulation of the stored data. The developed technology will establish a fundamental new paradigm in DNA data storage based on novel conceptual and experimental advances that integrate material science, robotic automation, micro-engineering and molecular editing of DNA.

What is the role for chromosome organization in determining cell identity?
Prof. Dr. Jop Kind (Hubrecht Institute)
Every cell contains 2 meters of DNA that needs to be condensed into the tiny space of a cell’s nucleus. This organization is unique to every cell and for new traits to arise different regions of the DNA need to become accessible and active. With this proposal we will investigate the coordination of this dynamic process by implementing new sensitive methods to study these events in single cells. This knowledge is essential to yield understanding of the mechanisms by which new cells arise during development and what the processes are that may result in establishing pathologies like cancer.

Resolving dangerous DNA structures
Prof. dr. ir. Puck Knipscheer (Hubrecht Institute)
The majority of the genetic material in a cell is folded into a uniform double helical structure as determined by Watson and Crick. Sometimes however, DNA folds into noncanonical shape that can be dangerous. This project reveals novel mechanisms that unfold these alternative DNA structures to ensure genome stability.

Shaping our memories: resolving the nanoscale organization of neuronal synapses in memory circuits
Dr. Harold. MacGillavry (UU)
Our memories shape who we are. However, we still do not fully understand how memories are stored in our brain. The researchers will use advanced microscopy techniques to uncover the structure of the connections between nerve cells, synapses. They will investigate how molecular changes in synapses underlie the formation of new memories. This research will yield valuable insights into how our memory works and could contribute to finding new ways to alleviate conditions such as Alzheimer's disease.

Dancing on ice
Prof. dr. ir. Ilja Voets (TU/e)
The ability of ice-binders to create and sculpt ice into tiny crystals with unusual shapes is unparalleled. The interaction with ice that is pivotal for this unique ability is not understood. TU/e researchers will use high-resolution microscopy to image how ice-binders dance on ice to understand how ice-interactive materials work and to unravel the ingredients and properties that enable regulation of ice formation and growth. This will lead to a blueprint for the design of new colloidal materials to prevent freeze-thaw damage and bring frozen cells and tissues back to life.

Transport in neurons
Prof. dr. L.C. Kapitein, Utrecht University
Long protrusions of neurons, axons, wire our nervous system. Their extreme length is enabled by motor proteins that transport cellular components over microtubules. Disruption of this process can result in disease. This research will use innovative microscopy to map the axonal roads and traffic rules in health and disease.

Stop-fix-go: dealing with roadblocks on the gene-track
Dr. M.S. Luijsterburg, Leiden University Medical Center
Protein machines that read our genes get stuck on damage in the DNA template. DNA damage must first be repaired before these protein machines can continue. How this works is currently unknown. The researchers will use genetic, cell biological and genome-wide methods to unravel how these processes work.

Filming the birth of intestinal tumors for finding new prevention methods
Prof. dr. J. van Rheenen, The Netherlands Cancer Institute
Preventing colorectal cancer is better than curing this disease. In this project, we will film the early steps of tumorgenesis and identify factors that can be targeted to decreased this risk. These experiments have the potential to identify novel ways to prevent or revert the risk of developing colorectal cancer.

You’re as cold as ice, but not willing to sacrifice your life?
dr. ir. Iddo Heller (VU)
What do space travelers, crop protection, organ- and food-preservation, and climate-change-related ice restructuring have in common? All involve solid-liquid mixtures in which thermodynamically driven (ice-)recrystallisation processes can cause harmful/fatal crystal growth. Nature has evolved ingenious ways to inhibit ice-recrystallisation, which allows insect survival even down to -70oC. We propose to use theory and single-molecule experiments to uncover how nature uses ice-binding proteins to control recrystallisation processes. Uncovering these fundamental principles for the first time implies a breakthrough with exciting potential applications in engineering (synthetic) protectants for use in cryopreservation, medical applications, and… perhaps even space travel.

TiLuminate: Illuminating the surface of Titanium Implants with Fluorescent Peptide Labels
dr. Roderick Tas (TUD)
Integration of 3D-printed titanium implants relies on seamless connection between its surface and the patient’s bone cells and tissue. However, fabrication results in large local variations in surface topography, directly affecting cellular function. Currently, the link between titanium surface structure and cellular response remains elusive because advanced fluorescent imaging techniques cannot visualize the local titanium surface. In this project, we will develop a fluorescent toolbox to illuminate titanium surfaces by super-resolution microscopy. This approach will accelerate our understanding of functional cellular responses to titanium surfaces and could pave the way to optimized surfaces for implants.

Read more >

Stiffness of cancer tissue impacts efficacy of immune therapies: 3D-printing meets T-cells
Dr. M. (Mahdiyeh) Nouri Goushki (Delft university of technology)
T-cell therapy, which deals with engineering immune (T-)cells to attack cancer cells, has shown great promises in treating blood cancers. T-cell therapy, however, has only been modestly successful for treating solid-tumors originating from either soft (e.g., breast) or hard (e.g., bone) tissues. This is because the mechanical properties of cancer tissues affect T-cells’ numbers and function, which is generally neglected in contemporary research regarding T-cell therapy. Here, I will engineer 3D-printed (micro)scaffolds with relevant mechanical and morphological properties as patient breast or bone tissues and address how such properties exactly affect T-cell proliferation and responses.

Shining light on growth and survival decisions in bacteria
Dr. J.H. (Johan) van Heerden (Free University Amsterdam)
Strikingly, a single molecule, named ppGpp, orchestrates decisions on growth and survival across bacterial species. Deciphering how this molecule encodes information in real-time and in living cells is currently impossible. Here we develop a biosensor based on fluorescence for direct measurements of this molecule in living bacteria. This sensor will allow us to “see” how ppGpp steers growth and survival decisions in individual cells. Importantly, it will make possible novel avenues to study the survival strategies of bacteria when confronted with growth-inhibiting challenges, such as antibiotics.

Dead or alive – investigating the possibility that hallmarks of disease arise after death
Dr. T. (Tessa) Sinnige (Utrecht University)
Diseases such as Alzheimer’s and Parkinson’s are characterised by the presence of dense protein deposits in the brain. Efforts to develop cures based on preventing or reversing protein deposition have failed thus far. In humans, protein deposits can only be studied upon brain dissection after the patient’s death. The researchers will use the transparent worm C. elegans as an animal model to visualise protein deposition over time in live animals. They will investigate whether protein deposits might form shortly after the time of death. This would greatly change our understanding of the disease mechanisms and the approach towards treatment.

https://www.nwo.nl/en/news/twenty-six-groundbreaking-research-projects-awarded-open-competition-domain-science-xs

Unravelling neuronal growth cone mechanobiology via sub-micrometric fabrication and super-resolution microscopy
dr. A. Accardo (Delft University of Technology)
Comparing the growth of healthy and diseased neurons is fundamental to understand and tackle neurodegenerative diseases (e.g. Alzheimer’s, Amyotrophic lateral sclerosis). The growth cone (GC) is a mechanosensitive structure, which probes the surrounding environment and connects neurons. To date, the GC has mainly been studied by employing unrealistic 2D bulky “petri-dish” configurations unable to mimic the brain microenvironment. We will pioneer a reproducible 3D GC model by combining 3D printed sub-micrometric biomaterials, able to simulate the geometrical and mechanical features in the brain, together with super-resolution microscopy. The results will pave the way for comparative studies involving diseased neurons.

Identification of proteins that protect DNA during extreme environmental conditions in diapaused killifish embryos and investigation of their application potential in human
prof. dr. E. Berezikov (Universitair Medisch Centrum Groningen)
Protection and repair of DNA is important to prevent cancer and delay ageing, and finding novel agents that can improve DNA protection in human is needed. African killifish Nothobranchius furzeri lives in ponds that dry out during a hot season. To survive the drought, killifish embryos enter into diapause, a low metabolic state with halted development, in which tissues and cells are highly protected from harsh environmental assaults by largely unknown mechanisms. This project will identify proteins that protect DNA from damage during diapause in killifish and test whether they can be used to improve DNA protection in human.

Innovative wound healing with 3D bioprinted living microalgae
dr. F. Gao (Wageningen University & Research)
Non-healing wound is a big social problem for 1-3% of the whole population, resulting in billions of medical care costs. Available wound healing dressing cannot solve the problem of bacteria colonization and local hypoxia, especially for chronic patients. An innovative idea of developing hydrogel dressing with photosynthetic microalgae is proposed to provide oxygen for faster skin-tissue repair and antibacterial exopolysaccharides. A microalga with high exopolysaccharides content will be three-dimensional bioprinted with hydrogel for wound healing dressing. The optimized dressing will be used for wound healing treatment with diabetic mice. This project will provide an innovative biological solution for wound healing.

High-throughput identification of bacterial RNA chaperone proteins
dr. D. Incarnato (University of Groningen)
RNA is a key molecule in most cellular processes. Many RNA’s functions are mediated by its ability to form intricate structures, a process known as RNA folding. A group of proteins called RNA chaperones has been proposed to assist the RNA in this process. By studying how the loss of these proteins affects the structure of the RNA inside bacterial cells we aim to understand the rules governing RNA folding. As RNA folding regulates protein production, by focusing on RNAs involved in cell growth and survival we hope to identify new targets for the development of more effective antibacterial drugs.

Enlightening large nanogaps to visualize biomolecules
dr. O.S. Ojambati(University of Twente)
The most powerful optical microscopes have now reached a plateau in their performance. This is because they use fluorescent labels to image biological structures. The labels also affect the properties of these bio-structures. A way to solve this problem is to use a nanogap which is a very efficient way to concentrate light but it only works for small molecules. When nanogaps are made larger to fit in large structures, the efficiency drops. If this problem is solved, nanogaps can be used to image proteins and viruses. This proposal aims to solve this problem by shaping light.

Interfacing with the nervous system at single-cell resolution for the next generation of artificial retinas
dr. D.G. Muratore (Delft University of Technology)
The next generation of artificial retinas will rely on electronics capable of reproducing the natural pattern of activation of the different neuron types with single-cell and single-spike resolution. They will need to calibrate the stimulation parameters based on the recorded neural responses in a closed-loop manner. However, due to the complex electrode-tissue interface, a stimulation artifact corrupts the recorded neural activity at different electrodes, severely limiting the calibration process. Here, we propose a new mechanism suitable for implantable massively parallel interfaces to mitigate artifacts using linear models of the electrode-tissue interface and convex optimization algorithms.

https://www.nwo.nl/en/researchprogrammes/nwo-talent-programme/projects-vici/vici-2021

https://www.nwo.nl/en/news/twentysix-groundbreaking-research-projects-launched-open-competition-domain-science-xs-2

Scrutinising antiviral interactions in real-time at the single particle level
prof. dr. W.H. (Wouter) Roos (University of Groningen)
Viruses chronically infect hundreds of million people every year leading to a large casualty rate. To date, for many viruses there is still no cure available. Potential antivirals have emerged to provide treatment for some of these virus-caused chronic diseases. However, the exact mechanism of these antivirals is not known. The proposed research aims to provide a detailed model of the interactions of antivirals with single viral particles, using advanced microscopy techniques. The results from this research will drive improved designs of antiviral candidates to fight viral diseases.

An atomistic view of living cells in hydrogel matrices
dr. A. (Anjali) Pandit (Leiden University)
Real-time analysis of metabolism and macromolecular structures in living cells would have tremendous benefits for disease diagnostics, drugs discovery and for optimizing microbial cell factories to produce specific compounds. NMR spectroscopy is a powerful, non-invasive technique for detection of various cell constituents however, live-cell applications have been limited to detection of soluble proteins and small molecules. We aim to overcome limitations using MAS solid-state NMR, and encapsulation of cells in hydrogel matrices for prolonged viability. If successful, the method will also provide a noninvasive way to characterize molecular structure and processes inside 3D bacterial biofilms or of gel-immobilized cellular organisms.

Extreme soft-hard interfaces
dr. M.J. (Mohammad J.) Mirzaali (Delft University of Technology)
Interfacing extremely soft extremely hard materials (e.g., hydrogel-metal) is one of the unsolved fundamental challenges in engineering. Nature offers smart solutions (e.g., functional gradient, hierarchy) to addressing those challenges. Inspired by natural solutions, we will design and fabricate biomimetic and sustainable interfaces through hybrid multi-material 3D printing. These optimized interfaces will have applications in artificial tendon-bone reconstruction and beyond across many industries.

A novel state-of-the-art intravital microscopy technique to track magnesium in the living kidney
dr. P.A (Pieter) Leermakers (Radboud University Medical Center)
Magnesium is an important nutrient for human body function. The amount of magnesium is tightly maintained, where the kidney is able to control how much magnesium is excreted into the urine and retained in the body. As it is currently impossible to look at this process inside living organisms, this project aims to develop a tailor-made state-of-the-art research technique that is able to study this process in living organisms for the first time ever. This technique will result in a magnitude of future applications, ranging from novel fundamental understanding of kidney function to identification of therapeutics that stimulate magnesium reabsorption.

Noise-reduction: an unconventional strategy to prevent antibiotic resistance
dr. M.K. (Maike) Hansen (Radboud University)
The emergence of antibiotic-resistant bacteria is one of the biggest threats to global food security, economic development, and health. A constantly increasing number of infections such as pneumonia tuberculosis, gonorrhoea and salmonellosis are becoming hard to treat due to antibiotic resistance. With antibiotic discovery stagnating, we must look for alternative solutions. One such solution is reducing so-called cellular noise. Noise is not just an involuntary consequence of biology, but bacteria harness noise as a diversification strategy to generate antibiotic tolerance. Here we propose a screen to identify noise-reducing agents that have the potential to prevent antibiotic resistance from developing.

https://www.nwo.nl/en/news/twenty-six-groundbreaking-research-projects-launched-open-competition-domain-science-xs-0

Dynamics of virus-like particles during respiratory fluid droplet evaporation.
Prof. dr. D. (Daniela) Kraft (LEI)Many respiratory diseases such as COVID-19 are transmitted through viruses in aerosols produced during breathing, talking or coughing. Predictive understanding of this transmission route remains limited because of the complex nature of respiratory aerosols, with their rapid evaporation generating additional complexities for viral stability. To make progress, it is essential to probe how key parameters such as polymers, humidity, temperature and ions act on viral stability via their influence on evaporative dynamics. By singling out and quantifying these parameters in a controlled experimental environment, we aim to improve our fundamental understanding of airborne virus transmission.

A multiscale study of the role of tissue mechanics in ultrasound-induced neuromodulation.
Dr. N.A. (Nicholas) Kurniawan (TU/e)

Focused ultrasound stimulation (FUS) is a relatively new and very promising tool for non-invasive brain stimulation with an improved spatial resolution and penetration depth, compared to conventional techniques. This technique is based on creating pressure waves and causing neurons to fire upon membrane deformation. However, a lack of understanding of the biomechanics of ultrasound neuromodulation at the cellular and tissue level has resulted in contradictory and inconsistent clinical outcomes. Here we propose to decipher the interplay between cells and tissue mechanics and FUS-induced functional responses, combining advanced bioengineering and mechanobiological tools.

A bottom-up approach to create synthetic tissue.
Dr. I.A.A. (Iain) Muntz (TUD)All tissues that make up our bodies comprise two distinct parts: living cells, which provide the biological activity to keep us alive, and a non-living extracellular matrix, a scaffold which confers mechanical functions. Our bodies undergo stresses throughout our daily lives: our knees compress with every step, while our lungs compress and decompress with each breath. How do different tissues of our bodies achieve the properties required for their function by combining cells and matrix in different ways? I will answer this question by building synthetic tissues, allowing me to study the contributions of cells and matrix separately and together.

Preventing proteins from sticky situations.
Prof. dr. L.M. (Liesbeth) Veenhoff (UMCG)One of the hallmarks of age-related diseases is the aggregation of proteins. Most of these proteins contain “sticky” domains that makes them prone to shift from a soluble state into liquid droplets and dysfunctional aggregates; a process called phase separation. How cells handle such sticky proteins is not totally understood. The aim of this project is to identify novel regulators of protein phase separation by performing an innovative large-scale microscopy-based screen in baker's yeast. The results will be highly valuable in the emerging field of phase transition regulation and could inspire new strategies for combating aggregating pathologies.

https://www.nwo.nl/en/news/twenty-eight-promising-research-projects-awarded-within-open-competition-enw-xs?utm_source=tripolis&utm_medium=email&utm_campaign=enw_nieuwsbrief_2023_06_01

SmartComplete: an ultimate approach for analysing complete transcriptomes, from bulk samples to single cells.
Prof. dr. Eugene Berezikov (UMCG)
Next-generation sequencing of RNA is now an integral part of nearly every genetic study where gene expression levels are relevant. Yet methods to generate libraries for RNA sequencing still need improvements in sensitivity, transcriptome coverage and costs. Here we propose a new approach, SmartComplete, which can simultaneously analyse the complete transcriptome of a cell, including messenger RNAs, non-coding RNAs and short RNAs, in a single one-pot library preparation, and at greater sensitivity and a fraction of costs of commercial kits. Once fully optimized, SmartComplete is poised to become the method of choice for all RNA sequencing applications.

Cancer-associated fibroblast subtypes: who does what?
Prof. dr. Alessandra Cambi (RUMC)
Solid tumours hijack neighbouring healthy cells to create environments that help tumour growth and spreading. Fibroblasts are cells that are present in all our organs and can be manipulated by the tumour. We know that these cancer-associated fibroblasts come in many types: some produce collagen and facilitate tumour invasion, others secrete molecules that fool the immune system helping tumours to escape. We do not know, however, the specific functions of these different types of fibroblasts. Here, we will develop new, reproducible and standardized procedures to induce these different fibroblast types in the laboratory to better understand their role in cancer.

Is there a molecular connection between acute myeloid leukaemia and nuclear transport?
Prof. dr. ir. Patrick R. Onck (RUG)
Acute myeloid leukaemia (AML) accounts for approximately 80% of all cases of adult leukaemia, with poor success rates for current treatments. Recently, a wide proteomic screening showed a remarkably strong connection between AML and nuclear transport, leading to the hypothesis that deficiencies in nuclear transport may play an important role in leukaemia. In the proposed research we aim to collect convincing molecular evidence to confirm this hypothesis. When successful, this will not only trigger a new research direction, it will also open up an entirely new angle in the development of therapeutic strategies for AML.

Reducing immunogenicity through bioengineering of human donor heart valves.
Dr. Marijn C. Peters (TU/e)
Children with heart valve disorders risk the development of heart failure and require valve replacement with a cryopreserved donor valve. However, these are avital and cannot grow. Living donor valves would offer excellent outlooks for growth but face immune rejection. Recently, we have pioneered a gene-editing system to hide donor valves from immune rejection. Here, we will validate by using advanced techniques to characterise bioengineered donor valves in the presence of immune cells to mimic implantation. When successful, this new technology will have large implications for modern transplant technology and may prevent the use of immunosuppressants/anticoagulants and extensive animal testing.

Drop-on-Demand Solution for Improved Tissue Engineering.
Dr. Sarah C.M. Pragnere (TU/e)
Tissue engineering combines biology and engineering to reproduce organs in vitro. Bioprinting of cells in hydrogels is one of the methods to produce these in vitro organs. While most methods aim to create homogeneous cell suspension, we believe that heterogeneous cell repartition can help us recreate some aspects at the micrometer scale that traditional methods cannot. This could be used to reproduce the specific micro-architecture of different organs. To achieve this goal, we want to use a drop-on-demand system to precisely position the cells in 3D. If it succeeds, it will pave the way for a new tissue engineering method.

High resolution volumetric bioprinting of large tissue models.
Dr. Alexis Wolfel (UT)
Laboratory-made tissues and organs are re-shaping medicine: they are useful to understand diseases; can reduce the use experimental animals; and may facilitate scalable organ transplantations. However, while natural tissues possess intricate architectures throughout their entire bulk, current methods to produce engineered living tissues only allow for either large volumes at low resolution or high resolutions within small tissue volumes. This limitation hinders the use of engineered tissues. We propose to develop a beyond-state-of-the-art 3D-printing technology to bioprint tissues with unprecedented speed and resolution. This novel technology will thus uniquely offer ability to rapidly produce large tissues at high resolutions.

Can AI learn the laws of physics and chemistry in protein folding?
Dr. Li Xue (RUMC)
Self-supervised learning (SSL) algorithms, like chatGPT, can learn the grammar of natural languages without giving specific instructions. We will develop 3D-GPT, an SSL algorithm that learns the physical and chemical rules of protein folding from the analysis of three-dimensional (3D) protein structures. Specifically, we will explore the capability of 3D-GPT to model the energy for protein folding and use it to fold small therapeutic proteins. Like other SSL algorithms, once pretrained, 3D-GPT can be fine-tuned to solve a wide range of applications, for example, identifying disease-causing mutations, and aiding cancer vaccine design.

https://www.nwo.nl/en/news/twenty-eight-promising-research-projects-launched-within-open-competition-enw-xs

2023/2024

Discovering cancer cell plasticity modulators
dr. M.M.K. Hansen (RU)
Cancer is one of the leading causes of death worldwide and resistance to anticancer treatment is the major cause for relapses in patients. Preceding permanent resistance, cancer cells can transiently enter a drug tolerant state that facilitates the subsequent emergence of resistance. Importantly, this drug tolerant state is not permanent––i.e., is reversible––a phenomenon termed plasticity. If and how we can target this plasticity still remains unclear. Here, we propose to identify plasticity modulators that can prevent drug tolerance from emerging. If successful, the discovery of plasticity modulators could open up highly-sought possibilities for preventing resistance.

Novel single-protein tool for developing antibacterial nanomedicines
dr. S. Pud (UT)
Bacteria create tiny protein spheres where they can isolate different chemical reactions from the rest of the cell. We want to highjack these protein spheres and use them as containers for delivery of drugs because they can be produced in large quantities and easily loaded with drug ‘cargo’. The only challenge is opening the spheres to release the drug in the right place. This is where our project comes in. We will build a special tool to study and optimize the release of cargo at the level of single protein nanocages.

2024/2025

Cracking the histone code with single-molecule nanopore sequencing
Xiuqi Chen (TUD)
Cellular DNA is wrapped around histone proteins with chemical modifications that are crucial for gene expression. It is extremely difficult to detect multiple co-existing modifications while pinpointing their genomic location. Existing methods either measure the DNA or the histone modifications separately. I aim to develop a method that, for the first time, can measure both simultaneously. I will covalently link histone proteins to the DNA and use nanopores to sequence DNA and histone modifications simultaneously at the single-molecule level! This innovative approach will provide unprecedented insights into histone modifications and gene expression, with major impact to human biology and medicine.

SF-TA: Towards scattering-free measurements in transient absorption spectroscopy
Volha Chukhutsina (VU)
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

Life under tension: relaxing membrane stress with a flippase DNA nanomachine
Cees Dekker (TUD)
Recently, scientists embarked on an incredibly ambitious goal: to build a living synthetic cell from the bottom up. Such a synthetic cell must be able to grow over time by incorporating new phospholipid molecules into its cell membrane. When administering lipids, they are however asymmetrically incorporated into one leaflet of the membrane, which leads to a stalling of growth and rupturing of the cells. Here, we propose to include a DNA-origami ‘flippase’ artificial enzyme that can flip lipids across the bilayer leaflets, enabling unlimited growth of mechanically stable synthetic cells, thus overcoming one of the major bottlenecks towards synthetic cells.

Screen for proteins that regulate variability in cancer cells
Maike Hansen (RU)
Despite advances in treatment, cancer continues to claim millions of lives globally, largely due to relapse after therapy. A key contributor to this relapse is the ability of cancer cells to enter a drug tolerant state that facilitates the subsequent emergence of resistance. Drug tolerance is caused by underlying variations in gene activity, also known as gene expression variability. If and how we can target variability remains unknown. This project will systematically identify protein regulators that influence gene expression variability. By pinpointing these master regulators, we will uncover new ways to block early stages of drug resistance in cancer.

Surface warming, salinity gradients, and microbial self-organization in marine systems
Uddalok Sen (WUR)
Rising surface water temperatures due to climate change are accelerating evaporation from marine environments. This intensifies the natural salinity gradient typically present in oceanic waters, with potentially dramatic effects on microbial ecosystems. One key process likely to be affected is bioconvection—a fluid motion driven by upward-swimming microalgae that influences nutrient distribution and microbial spatial organization. This project investigates how evaporation-enhanced salinity gradients alter bioconvection patterns in photosynthetic microalgal communities. By combining high-resolution imaging with mathematical modelling, we aim to uncover new insights into how surface warming may reshape microbial dynamics in marine ecosystems on both the micro- and macro-scales.

How to behave effectively?
Dr Anne Rios & Dr Efstratios Gavves (PMC/UvA)
T cells have a unique capacity to recognize and kill tumour cells. However, we still know very little about their specific behaviour that leads to effective elimination of cancer. In this project, we combine expertise in microscopy to follow T cells in space and time during tumour attack and computer vision to recognize behavioural patterns in the resulting microscopy datasets. In doing so, we hope to gain a better understanding of the behavioural strategy of T cells leading to elimination of tumour cells. In the future this information could be used to improve T cell therapy treatment for cancer patients.

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How does USP7 select its targets
Titia Sixma (NKI)
Here we study the regulation of USP7 to understand when and where it is active. We use a combined chemical and biochemical approach to create stable USP7 activation states in vitro. We will use biochemistry, structural biology and proteomics to analyze changes in activity, structure and interactome. This will give insight in the regulation of the crucial signalling enzyme.

The power of immune cells
Daan Vorselen (WUR)
Immune cells need to remove invaders and damaged materials from our bodies. We will develop new technology to observe the “table manners” of these cells. By measuring the forces that immune cells exert, we will precisely determine how they grab and engulf their targets. We will study this process in small transparent zebrafish. This will be the first time to observe how this process exactly proceeds in a living animal. By gaining a better understanding of the eating behaviour of immune cells, we will ultimately be able to better modulate it in disease.

Tell me how it begins, I will tell you how it ends: catching transcription at the start
David Dulin (VU)
To function, our cells need proteins, which are made by ribosomes, which are partly constituted of ribosomal RNAs synthesized in our cells by RNA polymerase 1 (Pol I). Pol I activity is essential during cell growth, and central in the development of many cancers. Ribosome assembly is mainly regulated at the start of ribosomal RNA synthesis by Pol I. Here, we will employ cutting edge biophysics techniques to reveal how this process is controlled one Pol I molecule at a time.

A kill-switch as bacterial immune system
Daan Swarts (WUR) & Chirlmin Joo (TUD)
Just like humans, bacteria use immune systems to protect themselves against viruses. A recently discovered bacterial immune system named ‘SPARTA’ can recognize viral DNA, after which it will sacrifice the bacterial cell to prevent spread of the virus. We will investigate how SPARTA specifically recognizes the viral DNA, and which checkpoints it needs to pass before this ‘kill-switch’ is activated, without inducing autoimmunity. By comparing SPARTA mechanisms to mechanisms of other immune systems we will enhance or our understanding of bacterial immune systems. This will contribute to the development of programmable virusdetection tools.

A Twist in the Tail: Exploring Chiral Interactions in Liquid Crystals for Biosensing
Lisa Tran (UU) & Siddharth Deshpande (WUR)
There is an urgent need to make biosensors fast, affordable, and sensitive, while maintaining molecular specificity. Here, we will use liquid crystals, famous for display technologies, to produce color-changing emulsions as biosensing platforms that address these needs. Using high-resolution microscopy, spectroscopy, and lab-on-a-chip technologies, we will systematically characterize how chiral liquid crystals are impacted by target molecule structures to produce diverse color-changing signals. Beyond the innovation of accessible, specific, and quantitative biosensors, our findings will shed light on chiral organization in crowded environments, relevant to biological systems.

Protein Detective: An Automated Pipeline for Identifying Unknown Proteins in Cryo-Electron Microscopy Densities
Prof. Dr. Alexandre Bonvin (UU)
Visualising proteins, ideally in their cellular environment, is a first step toward understanding their function. This can be done using cryo-electron microscopy. The resulting 3D images are, however, not always of sufficient quality to identify the proteins hidden in those. In this project the researchers will build an automated “protein detective” pipeline that will combine all available clues on the system, together with AI-generated protein models to build reliable 3D models of intricate molecular machine in which all components are identified.

Understanding the Collective Patterns of Active Polymer-like Matter
Dr. Sara Jabbari-Farouji (UvA)
Can we model the spectacular patterns of collective motion in birds and fishes? While simple statistical physics models successfully explain collective phenomena in some autonomous systems, real life is more complex. For example, biopolymers in the cell and blobs of entangled worms are not rigid, as assumed in models. We will develop new theoretical and computational methods to understand patterns of collective behavior of semiflexible active filaments. This will help us understand the biological function of collective self-organization and to uncover principles for designing smart filament-like materials with dynamic capabilities like shape-shifting or self-healing.

‘Breaking the silence’: understanding DNA repair in facultative heterochromatin
Dr. Aniek Janssen (UMCU)
This proposal aims to understand how cells repair damaged DNA. DNA damage can lead to diseases such as cancer, and understanding how our cells repair the damage could help develop new treatments. Sometimes damage occurs in a part of our DNA that is "switched off" and doesn't have any active genes, which is called "facultative heterochromatin." We want to understand how our cells repair damage in this specific part of the DNA. To do this, we will use fruit flies as a model to study how DNA repair is executed in heterochromatin.

Synthetic fuel cell from biomolecular components
Prof. Dr Bert Poolman (RUG)
Biological life is driven by fluxes of energy and matter in cellular systems that are hugely complex in their composition and structure. The exchange of molecules between cells and the environment requires well-balanced fluxes to support growth and homeostatic conditions. We design and study such ‘out-of-equilibrium’ systems, to resolve the minimal mechanisms that allow a living cell to sustain itself. We construct synthetic cells with dual membrane systems for sustainable production of ATP, generation of a proton motive force and pH homeostasis, using a bottom-up molecular systems approach.

How does a virus assemble itself
Prof. Dr Wouter Roos (RUG)
To make a simple viral particle, one only needs to mix the viral protein building blocks with the genome. By itself a viral nanoparticle will be formed in this solution. This sounds easy, however we still don’t know why and how this functions. Using advanced microscopy approaches the researchers will now tackle this problem to try to understand how a virus forms itself.

Visualizing a memory
Prof Dr Helmut Kessels & Dr Ir Joachim Goedhart (UvA/UvA)
A wealth of memories is stored in our brain. How is it possible that we are able to bring one particular memory to our attention, while all other memories remain stored in our brain? This project studies the mechanisms that underlie the retrieval of a specific memory. We use advanced techniques that enable use to visualize the activation of a memory code. This research is important to understand what goes wrong when suffering from memory problems, as is seen in Alzheimer’s disease.

Visualizing viral infection one virus at a time
Dr Marvin Tanenbaum (Hubrecht Institute)
When two people get infected by a virus, one might get very sick, while the other has no symptoms at all. The outcome of viral infection is equally heterogeneous at the cellular level. What causes this heterogeneity in infection outcome is poorly understood. Here, we will use innovative new microscopy techniques to study infection of host cells by single viruses to understand what determines the success of infection. The outcomes of this work will provide a better understanding of viral infection heterogeneity and can potentially contribute to the development of improved antiviral drugs.

Disassembling the morse code of our body
Dr Katharina Sonnen (Hubrecht Institute)
Cells within our body communicate with each other to orchestrate development and maintenance. Cells use something like a “morse code” to transfer information accurately and efficiently, but we do not understand the underlying mechanism. Here, we will disassemble the parts to reveal its functionality and enable future therapeutic targeting.

The Travels of mRNAs in fungi
Dr Evelina Tutucci & Prof dr Han Wösten (VU/UU)
Fungal infections are on the rise worldwide. In addition, resistance to the antifungal drugs currently used in the clinic is increasing. Therefore, new antifungal agents need to be developed. In this project we will investigate the two main human fungal pathogens, Candida albicans and Aspergillus fumigatus. By using advanced microscopy, we will explore whether and how the localization of mRNA molecules impacts the growth of hyphae, elongated cells important for infection, as well as their ability to infect human cells. This work could therefore provide targets for the development of new antifungal agents.

Getting in shape for neuronal health
Dr Ginny Farias Galdames (UU)
In our brain, neuronal cells have different organelles with specific tasks, essential for the development and function of our brain. In particular, the endoplasmic reticulum (ER) is a large organelle with multiple tasks, and its shape (tubule or sheet) determines what tasks are needed in a given moment. In several neurological disorders, the ER cannot get in the correct shape, causing neuronal death. By using imaging and proteomics techniques, this project will determine how the ER shape is regulated in neurons. This knowledge could help to re‐shape the ER in neurological disorders.

Location, location, location - how inhibitory immune receptors initiate and relay their signals to dampen activation
Prof. dr. Linde Meyaard & Dr Kristina Ganzinger (UMCU/AMOLF)
A healthy immune system clears microbes without damaging the body. For this purpose, immune cells are regulated by inhibitory receptors that serve as a break on activation. The exact mechanism of how inhibitory signals are sensed by immune cells and how this can dampen many different activation signals is not understood. In this project, immunologists team up with biophysicists to visualize and follow individual receptors in immune cells using a very powerful microscope. In this way, the fundamentals of inhibitory signalling will be resolved, which will support development of drugs that target inhibitory receptors in cancer and inflammation.

https://www.nwo.nl/en/news/eighteen-inventive-research-projects-launched-through-open-competition-domain-science-m

The Great Escape of tuberculosis
Dr. Nicole van der Wel & Dr. Coen Kuijl (AUMC/AUMC)
Tuberculosis is the deadliest bacterial infectious diseases worldwide. The bacterium infects exactly those immune cells that try to eliminate it. Crucial for a successful infection is the escape from the degradative compartment in these immune cells. Here researchers will develop a new method (MyCo-TrAP), to coat tuberculosis bacteria with the proteins that help the bacterium to escape. Thereby, they will better understand the mechanism of immune recognition and escape of tuberculosis. Once successful, the method has the potential to aid in the development of vaccine strategies for TBC but also bladder cancer and viral infections.

Viral or not viral, that is the question
Dr. David Dulin (VU)
The cells of our body are equipped with a defensive arsenal against microbial infection. Part of this arsenal is the detection and signalling of double-stranded RNA (dsRNA), a hallmark of RNA virus infection, to induce the production of small antiviral molecules. A protein called MDA5 has a key role here: it specifically detects and binds to dsRNA to signal to the cell the infection. This proposal will use cutting edge biophysics technologies to reveal the mechanism by which MDA5 interrogates RNA to protect us against viral infection.

Novel microscopy to catch molecular motors on the move
Dr. ir. Carlas Smith & prof. dr. Nynke Dekker (TUD/TUD)
We will design and build a novel high-throughput single-molecule instrument that enables insight into the composition and dynamics of molecular motors on DNA molecules at high spatiotemporal resolution. The instrument design benefits results from a synergetic combination between novel hardware and information processing tools specifically tailored to maintain simplicity and effectivity. We will employ the instrument to obtain novel insights into how the composition and motion of our DNA copying machinery are orchestrated in space and time. Multiple other applications of the instrument can also be foreseen.

https://www.nwo.nl/en/news/twenty-two-innovative-research-projects-launched-through-open-competition-domain-science-m-programme

Understanding Tubulin Detyrosination: Mechanism, Structure and Function
Prof. Thijn Brummelkamp & Prof. Anastassi Perrakis (Netherlands Cancer Institute/Netherlands Cancer Institute)
The skeleton of our cells consists largely of microtubules, polymers that consist of alpha and beta tubulin dimers. Microtubules play an important role in the transport of molecules within the cell and are also the target of commonly used therapeutics such as chemotherapeutics (taxanes). Microtubules are modified in various ways, giving them different properties. The first modification described is detyrosination but the responsible enzymes remained unknown. Now, after more than 40 years, we have discovered these enzymes allowing us to study their mode-of-action and the importance of this modification.

How do we package newly copied DNA?
Dr Francesca Mattiroli (Hubrecht Institute)
Every day, billions of cells divide in our body. As the cells divide, they need to maintain their function to prevent the onset of diseases, such as cancer. Cell function is determined by the DNA and its packaging system. So, when cells divide, they need to inherit a copy of the DNA in the right packaging format. How this is controlled remains unclear. The team will visualize how key proteins responsible for packaging newly copied DNA perform their function. The work will provide fundamental knowledge on how to target this process in disease.

Molecular antibiotic fishing rods to decipher resistance
Dr Willem Velema (RU)Antibacterial resistance is a major threat to human health worldwide. Here, we will decipher mechanisms that bacteria use to evade antibiotics. We will chemically modify antibiotic drugs to turn them into molecular fishing rods to catch RNA. After applying them to bacteria we will analyse what we caught, which can tell us how bacteria utilize RNA to become resistant. By using this information we expect to develop radically different strategies for fighting resistance.

Pioneering chromatin: interaction of pioneer proteins with native, genomic nucleosomes
Dr Hugo van Ingen (UU)
Nucleosomes are the building blocks of chromatin and essential to switch off genes that are not needed by a cell. This way the identity of a cell, e.g. a liver vs. neuron cell, is determined. So-called pioneer proteins can however bind nucleosomes to activate these genes, thereby transforming cell types and even changing “adult” cells to stem cells. In this project, we will use NMR spectroscopy and biochemical techniques to unravel how pioneer proteins bind native, genomic nucleosomes. This will be useful to improve cell fate conversions and regenerative therapies.

On the origin of cristae
Dr Taco Kooij (RUMC) & Prof. Laura van Niftrik (RU)
The inner membrane of mitochondria, the powerhouses of the cell, is characterized by invaginations, termed cristae. Malaria parasites harbour a single, unusual mitochondrion that lacks cristae during the pathogenic blood-infection. After formation of sexual-stage parasites, required for transmission to the mosquito vector, mitochondrial functioning changes dramatically and cristae are formed from scratch. The investigators will employ cutting-edge live- and electron microscopy to provide an unparalleled 4D-reconstruction of cristae formation in this unique biological system. By combining these insights with data on protein complexes, they will shed light on this validated antimalarial drug-target and on basic principles of cristae formation.

Filming cell division using AI
Dr Rifka Vlijm (RUG)
During cell division each daughter cell should receive one DNA copy. Microtubules divide the DNA by pulling on it. Therefore, which microtubule binds to which DNA molecule is crucial. How the protein complex called corona organizes this binding remains a mystery as it is too small and dynamic to be detected by ordinary microscopes. The researcher solves this by imaging fixed cells in low- and high-resolution using a super-resolution-microscope. Next, low-resolution movies in living cells (=faster and less damaging) are translated into super-resolution using AI, to finally film how the corona ensures robust genome inheritance.

Exposing a motley enemy hidden under a smart blanket: elucidating Candida albicans biofilm formation using highly-sensitive fluorescence microscopy.
Dr Evelina Tutucci (VU)
Candida albicans is a commensal inhabitant of our flora found in the microbiome of 40-60% of healthy adults. In immunocompromised individuals, however, C. albicans overgrows, causing deadly systemic infections. Its virulence is linked to albicans ability to change its morphology and switch from a single cell form, to a filamentous form and to build-up multicellular drug-resistant structures called biofilms. How these morphological changes occur is still largely unclear, impairing the development of much-needed therapies. With this research, we develop highly sensitive fluorescence microscopy tools to elucidate the molecular events controlling how single pathogenic fungi change their morphology to build biofilms.

https://www.nwo.nl/en/news/fourteen-innovative-research-projects-launched-through-open-competition-domain-science-m-0

https://www.nwo.nl/en/news/twenty-six-innovative-research-projects-launched-through-open-competition-domain-science-m

Role of the cellular cytoskeleton in membrane electroporation and cargo translocation (ROCKET)
Dr Pouyan Boukany & Prof. Gijsje Koenderink (TUD/TUD)
CRISPR-Cas is a revolutionary new technology which enables researchers to make fast, affordable and precisely targeted changes in the DNA of living cells. Congenital diseases can thus be treated at the source by repairing genes. Widespread application is however currently hampered by the fact that the CRISPR-Cas proteins need to be safely introduced into cells together with DNA or RNA, without cell damage. Here a multidisciplinary team of researchers will study how they can overcome the barrier posed by the cell membrane with electrical pulses, combining experiments and computer models.

https://www.nwo.nl/en/news/seventeen-innovative-research-projects-launched-through-open-competition-domain-science-m-1

The art of the first cut: elucidating the molecular mechanism of the signal peptidase complex
prof. dr. Friedrich Förster (UU)
Many proteins such as the protein hormone insulin and antibodies have ‘zip codes’ that ensure their correct delivery in the cell. Signal peptides constitute these zip codes, and they are removed from the proteins shortly after reaching their first destination, from which they are transported further. In this project we investigate how the enzyme that is responsible for the correct removal of the signal peptide works in atomic detail. This research is important to understand how essential proteins such as insulin are produced in a healthy cell, but also to obtain clues into how viruses hijack the enzyme for reproduction.

Understanding the master chaperone of our cells
dr. Sonja Schmid & dr. Kasia Tych (WUR/RUG)
Proteins constitute the molecular machines in our cells. However, many of them would be non-functional without the help of the cell’s master chaperone, Hsp90, which turns them into functional entities. Surprisingly, despite this central role, we still don’t understand how this Hsp90 actually works. We will therefore use new technology to elucidate the relevant small scale of individual molecules. We will test how Hsp90 is energetically powered, how it treats the other proteins, and how it coordinates its necessary helper proteins. Our research will provide a currently missing molecular-level understanding of Hsp90 and thus inform the development of cancer therapeutics.

https://www.nwo.nl/en/news/pre-announcement-new-round-open-competition-domain-science-m-0

Visualizing single RNA polymerase complexes upon DNA damage
Dr. ir. Jurgen Marteijn & Dr. Tineke Lenstra (EMC/NKI)
Damage in the DNA inhibits transcription of genes by RNA polymerase II, which copies the genetic information of the DNA into RNA. This inhibition of RNA polymerases results in severe cellular dysfunction and accelerated aging. In this proposal, we develop a novel microscopy-based approach that can measure the effects of DNA damage on individual RNA polymerase complexen in living cells. Using this approach, we will be able to discover what exactly happens to RNA polymerase when it encounters DNA damage, and how this affects transcription of genes.

How neurons achieve life-long memory of their identity.
Dr. Jeroen van Zon & Dr. Gert Jansen (AMOLF/EMC)Neurons existing in many different kinds and are not renewed during our lifetime. How do neurons ensure that during this entire time they never accidentally lose their cell type identity? The researchers use microscopy, behavioral analysis and computer simulations to uncover the mechanisms that form this memory in the neurons of a simple worm. Because the structure of the molecular networks that form this memory are conserved from worm to man, this project will also give insight into the memory of human neurons and how this is possibly perturbed in neurodegenerative disease.

Man-made microswimmers in 3D.
Dr. Hanumantha Rao Vutukuri (UT)Autonomous motion, activity, and transport of microorganisms in fluids are the hallmark features of living systems. In recent years, this has fueled an emerging new research field, namely ‘’active matter,” focused on designing synthetic microswimmers with unique capabilities such as self-propulsion, assembly themselves, and response to local environments. But making micron-sized artificial building blocks that are capable of swimming on their own in 3D is challenging. We will develop a new model system to better understand the dynamic self-organization of microorganisms in 3D using optical microscopy techniques.

How do transcription factor proteins choose their partners?
Prof. dr. ir. Richard Immink & Dr. Aalt-Jan van Dijk (WUR/WUR)To regulate gene activity, proteins named ‘transcription factors’ work together with specific partner proteins in complexes. Identification of these specific partners is essential to understand which genes can be activated or repressed, but currently requires time-consuming laboratory experiments. However, the recently produced wealth of genome information, in combination with the advances in artificial intelligence, now enable the development of computer models that can predict protein-protein interactions. Here, we will combine artificial intelligence with laboratory experiments to develop a robust computer model that can reliably predict plant protein-protein interactions.

https://www.nwo.nl/en/news/nineteen-innovative-research-projects-launched-through-open-competition-domain-science-m-programme

Break and make: the route to self-healing
Dr. Camilla Terenzi & Dr. Thomas Kodger (WUR/WUR)In nature, biological materials, such as living tissues, are universally capable to self-repair even under constant load, while man-made materials, once deformed, cannot spontaneously re-form. The mission of scientists, inspired by these natural systems is to realize, in novel materials, the intricate dance between the chemistry and the hierarchical mechanics of reversible molecular bonds, at the core of self-healing. In this project, the researchers will quantify the real-time breaking and recovery of smart materials, capturing the whole range of length scales whose interplay has thus far remained elusive, by means of newly developed experimental methods.

Survival of the fittest
Dr. Saskia Suijkerbuijk (UU)
The cells in our body are in a constant battle. Through removal of less fit cells, tissues can make sure they remain strong. Sometimes, this process does not go as planned and this causes disease. For example, tumors can use this mechanism to enhance their growth. To better understand how the interaction between tumors and the surrounding organ tissue works, the researchers will study how cells talk to each other. This allows us to learn which molecules are involved in the formation of tissues and how tissues can remain healthy.

https://www.nwo.nl/en/news/twenty-one-innovative-research-projects-awarded-through-open-competition-domain-science-m-programme

2023/2024

Does molecular clutter cause trouble during aging?
Dr Tessa Sinnige & Dr Arnold Boersma (UU)
Living cells are densely packed with large molecules such as proteins and DNA. As molecules are fighting for space inside the cell, they may accidentally clump together. Clumping of proteins is associated with diseases such as Alzheimer’s and Huntington’s, but also occurs during regular aging. In this project, the researchers will measure the packing of molecules inside a small worm that is often used as a model organism in biology. They will investigate whether cells of the worm become more crowded as the animal gets older, and whether this indeed causes protein clumping.

2024/2025

SuperAssembly: Tunable high-speed self-assembly at the super-resolution
Uddalok Sen (WUR)
The evaporation of a ﬂuid volume containing dispersed colloidal particles can be harnessed to develop bottom-up materials in a process known as evaporation-induced self-assembly. While most prior research has focused on the ﬁnal structure of the self-assembled particles in multicomponent systems, how the particles arrive at the interface remains largely unexplored. Through high-speed super-resolution microscopy experiments, this project aims to unravel the self-assembly dynamics in a unidirectionally evaporating binary liquid containing a binary colloidal dispersion. The ﬁndings of this project will provide fundamental mechanistic insights into tunable colloidal self-assembly by modulating the liquid composition, particle shape, and particle interactions.

How nanoplastics change proteins
Sander Woutersen (UvA)
Plastic nanoparticles are everywhere, including in our own bodies, and there is increasing evidence that these nanopar-ticles aﬀect our health. The biological eﬀects of nanoparticles are ultimately due to their interaction with proteins, the molecules that catalyze all reactions in the cell. However, whereas intensive research is being done on the bio-logical eﬀects of plastic nanoparticles, very little is known about the underlying nanoplastic-protein interactions that give rise to these biological eﬀects. In this project, we use advanced spectroscopy methods investigate how plastic nanoparticles change the structure and aggregation behavior of proteins.

Approaching De-Novo Life
Prof Sijbren Otto (RUG)
Co-applicants: Siewert-Jan Marrink (RUG); Anouk Rijs (VU); Evan Spruijt (RU); Sabeth Verpoorte (RUG)
The researchers aim to create, for the first time, a minimal form of life from synthetic molecules. They will take a system that is able to replicate (i.e. make copies of itself) and metabolize (construct its own components from material in its environment) and make it produce its own cell-like compartments. They will then make these systems grow and divide and undergo Darwinian evolution. The research involves a collaboration between experts in chemistry, microfluidics, mass spectrometry, computer simulations, and early evolution theory. This work touches on existential questions like: “Why is there life?” and “Why are we here?”.

Holey trap – disordered proteins guard the gap
Prof Patrick Onck (RUG)
Co-applicants: Liesbeth Veenhoff (RUG), Cees Dekker (TUD), Rifka Vlijm (RUG)
The transport proteins in cells are highly selective, transporting only those molecules that have precisely the right shape: structure determines function. Until recently the nuclear pore complex, a large transport system to access the cell nucleus, was the only exception to this. Its selectivity for transport arises from a unique filter system based on unstructured proteins. Now, recently, a second filter system has been found (in peroxisomes) that works similarly but at a drastically reduced complexity. In this research programme we combine biological, physical and chemical methods to use this exciting opportunity to uncover how these filters system actually work.

How developing embryos use noisy clocks to tell time with high precision
Jeroen van Zon (AMOLF)
Co-applicants: Marianne Bauer (TUD); Alexander van Oudenaarden (Hubrecht); Rik Korswagen (Hubrecht); Jacques Bothma (Hubrecht); Marie-Anne Félix (CNRS)
During our embryonic development, each cell divides and differentiates at exactly the right time. However, how cells keep track of time is largely unknown, mostly because these processes are difficult to follow in most types of embryos. In this project, we will solve this fundamental question by studying the timing of cells in the simple nematode worm C. elegans, using novel biological techniques and theoretical concepts from physics. A better understanding of the mechanisms cells use to measure time will be crucial for applications in regenerative medicine and provide novel insight into the emergence of birth defects and other diseases.

Joining Forces for Human-Made Molecular Machines
Iddo Heller (VU)
Co-applicants: Ben Feringa (RUG); Jocelyne Vreede (UvA); Jan) Lipfert (UU); Chase Broedersz (VU) ; Shirin Faraji (RUG)
In all forms of life, molecular motors are indispensable for transporting molecular building blocks inside cells, for maintaining DNA, and for generating (muscle-based) motion. Only recently, mankind has developed the ability to build synthetic molecular motors and machines and to control these with light. In this project, researchers from various disciplines will join forces to unravel the design-principles of synthetic nanomachines, to design motorized nanoscale building blocks and to demonstrate the first light-controlled artificial muscles and conveyor belts. These discoveries enable mankind to pursue new applications such as in nanomedicine and in the design of adaptive, mobile, and self-healing materials.

On Form and Growth: Understanding microtubule structure and dynamics at the nanoscale
Main applicant: Prof. dr. A.S. Akhmanova (UU)
Co-applicants: Prof. dr. L.C. Kapitein (UU), Prof. dr. A.M. Dogterom (TUD) , Dr. T. Zeev-Ben-Mordehai (UU), Dr. S.C. Howes (UU), Dr. A.J. Jakobi (TUD)
Microtubules are tiny cellular tubes, which form rails for transport inside cells, drive cell division and allow cells to move. Understanding microtubule organisation and function is important because microtubules are perturbed in different human diseases and can be targeted to treat cancer and inflammation. In this project, we will combine advanced light and electron microscopy techniques to better understand how the structure and dynamics of microtubules are related at the molecular scale and how this underlies their biological functions.

In search of the coronavirus Achilles’ heel
Main applicant: Dr. D. Dulin (VU)
Co-applicants: Prof. dr. F.J.M. van Kuppeveld (UU), Prof. dr. ir. G.J.L. Wuite (VU), Prof. dr. W.H. Roos (RUG), Dr. R. Vlijm (RUG), Dr. M. Bauer (TUD), Dr. S.M. Depken (TUD), Dr. R.J. de Groot (UU)
COVID19 is the disease resulting from SARS-CoV-2 infection and is responsible for the ongoing pandemic. Though vaccines are available, we need to understand how the virus replicates within the cell in order to develop new antiviral drugs. New drugs will protect people against lengthy hospitalizations, long-COVID, and future new variants that make vaccinated people ill. We will investigate the coronavirus Achilles’ heel, namely how coronaviruses multiply their genetic material and how genetic material is packed into new viral particles. We bring together an interdisciplinary team of biologists,experimental- and theoretical physicists to uncover the very early stages of coronavirus infection.

How do the first lineage decisions of cells take place during early embryogenesis?
Main applicant: Dr. H. Marks (RU)
Co-applicants: Prof. J.H. Kind (Hubrecht), Dr. T.L. Lenstra (NKI), Dr. R van Amerongen (UvA), Dr. ir. S.J. van Heeringen (RU)
How one cell, the fertilized egg, can faithfully develop into an organism with many different cell types is one of the most fascinating questions in biology. An important step takes place in the early embryo, when it is still a small clump of seemingly equal cells. A diverse team of top researchers will use detailed molecular analyses to investigate when and how these individual cells decide their future. This will provide fundamental new insight into how cells make decisions. It will also help with developing innovative strategies in cancer and stem cell research, and improve our understanding of developmental defects.

Unravelling proteins one by one with nanopores
Main applicant: Prof. dr. G.M. Maglia (RUG)
Co-applicants: Prof. dr. C. Dekker (TUD), Dr. S. Schmid (WUR)
Proteins are the workhorses in our cells. Yet, we still miss lots of information on these fundamental molecules of life. We will develop new nanopore technologies to tackle the main challenges in protein analysis: to count and identify proteins, to read off their basic code at the single-molecule level, and to resolve the temporal shape changes of individual proteins that underlies their function. Unravelling proteins one-by-one by resolving their sequence and functional dynamics provides extraordinary potential to radically advance our understanding of proteins.

Advanced bioengineering strategy for production of human miniature hearts
Prof. dr. P.C.J.J. Passier (UvT)
Co-applicants: Prof. G.J.C. Veenstra (RU), Dr. ing. J.N. Post (UvT), Dr. JCH Leijten (UvT)
Cardiovascular diseases are the number one cause of death worldwide. Current animal and cell culture models are not accurate enough to sufficiently predict the efficacy and toxicity of drugs. In this research proposal, we use an ultra-high-throughput platform that allows us to encapsulate and culture human stem cells in hollow microgels. Using single cell analysis of regulatory pathways in combination with predictive computational modelling, we aim to differentiate cells into miniature hearts, resembling the structure and function of the human heart. This allows us to use a screening platform of human miniature hearts for studying heart disease and testing drugs.

https://www.nwo.nl/en/news/twenty-one-innovative-research-projects-launched-through-open-competition-domain-science-xl

IMAGINE!: Seeing and steering cells in our tissues
Full project title (IMAGINE! Innovative Microscopy and Guidance of Cells in their Native Environment
The main applicants are Anna Akhmanova (UU), Peter Friedl (RadboudUMC), Jacco van Rheenen (NKI and Oncode Institute), Madelon Maurice (UMC Utrecht and Oncode Institute), Geert Kops (Hubrecht Institute and Oncode Institute) and Lukas Kapitein (UU). Also involved are researchers from TU Delft, TU Eindhoven, Prinses Máxima Centrum and ErasmusMC, and various microscopy centres, including the UU’s Biology Imaging Center.
Cells, life’s basic building blocks, have been extensively studied, but how cells self-organise into tissues and how molecular processes inside cells enable tissue formation is poorly understood. IMAGINE! will bring together biology and technology experts to address this major challenge by studying and manipulating cells at the molecular level in their native tissue environment. The programme will provide essential knowledge and tools for regenerative medicine, optimising therapies and repurposing existing drugs.

PRELIFE - Pathways, Reactions, and Environments leading to LIFE: An interdisciplinary approach
Coordinator on behalf of the consortium: Prof. Dr I.L. ten Kate (Utrecht University)

Consortium: Amsterdam University of Applied Sciences, Avans Hogeschool, Dutch Society for Theoretical Biology(NVTB), Frederic Petrignani, Marieke Baan Wetenschapscommunicatie, Naturalis Biodiversity Center, Netherlands eScience Center (NLeSC), NextNature, SRON, Radboud Universiteit Nijmegen, Rijksuniversiteit Groningen, Studio HB , Technische Universiteit Delft, Universiteit Leiden, Universiteit Twente, Universiteit Utrecht, Universiteit van Amsterdam, Vrije Universiteit Amsterdam

The origin of life is one of science's greatest unsolved puzzles. Several theories exist, but there is no consensus. PRELIFE is built on an interdisciplinary approach in which astronomy, biology. chemistry, computer science, earth and planetary sciences, education science, mathematics, and physics work together on the question 'How and under what conditions did life arise on Earth, and how common are these conditions in the universe?' These questions are also alive in society, which is why teachers, schoolchildren and the public will be involved in the search for answers, through educational projects and collaborations with artists and museums.

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CURE4LIFE: Development and societal impact of stem cell based genetic medicines
For a number of rare genetic diseases, lifelong cure can be obtained by correcting the genetic defect in the patients’ own blood stem cells. Many curative gene therapies do not reach patients for reasons other than a lack of treatment quality. The consortium proposes to develop platform infrastructure that can be used for many diseases rather than every time focusing on one approach unique for each disease. Simultaneously they address challenges regarding the regulation, reimbursement and public acceptance of these therapies in a knowledge hub for dialogue with society.
Consortium: Leiden University Medical Center, Erasmus MC, VU Amsterdam, Utrecht University, Leiden University, Avans University of Applied Sciences, UMC Utrecht, Radboud university medical center, Radboud University, Batavia Biosciences, ISHEO, Spierziekten Nederland, Prinses Beatrix Spierfonds, Miltenyi, Oscar Nederland, Foundation for Immune Disorders (SAS), Patiëntenvereniging voor Stofwisselingsziekten (VKS), Stichting Alexander, National Health Care Institute (Zorginstituut Nederland), IPOPI - International Patient Organisation for Primary Immunodeficiencies. Official secretary on behalf of the consortium: prof. dr. F.J.T. (Frank) Staal – Leiden University Medical Center (LUMC)
Amount awarded: 5.0 million Euro

CureQ: Predict, Delay & Cure polyglutamine(Q) caused neurodegeneration
There are over ten inherited neurodegenerative disorders that are caused by a similar DNA mutation, including Huntington’s Disease. Recent trials are hopeful but also leave many questions. What is the best moment to start therapy? Can we predict age-of-onset more accurately, and do gene-carriers want to know this? Are there alternative therapeutic strategies possible that don’t require repeated lumbar injections? What does this all mean for very young patients? Researchers from academia and biotech, neurologists, lecturers and patient foundations aim to answer these questions together, with a personalized treatment as the ultimate goal.
Consortium: Amsterdam UMC - Location AMC, Radboud university medical center, Erasmus MC, Hanze University of Applied Sciences, Leiden University Medical Center, VU Amsterdam, Princess Máxima Center for pediatric oncology, University Medical Center Groningen, Amsterdam University of Applied Sciences, Maastricht UMC+, Proefdiervrij, Campagneteam Huntington, Vico Therapeutics, ADCA/Ataxie Vereniging, VectorY, Vereniging van Huntington. Official secretary on behalf of the consortium: prof. dr. E.A.J. (Eric) Reits - Amsterdam UMC - Locatie AMC

NANOSPRESSO-NL: Local preparation of high-quality, personalized nucleic acid nanomedicines
NANOSPRESSO-NL specifically addresses the current mismatch between personalized therapeutic strategies and industrial centralized large-scale manufacture of medicines. The NANOSPRESSO-NL consortium is convinced that nucleic acid therapeutics are uniquely qualified for production in local hospital pharmacies in response to the needs of the individual patient. By switching towards a fully standardised platform formulation, quality control can be centred around the production process rather than the end product, quite similar to a popular method of decentralized high-quality espresso making.
Consortium: UMC Utrecht, University of Twente, Saxion University of Applied Sciences, Leiden University Medical Center, Princess Máxima Centre for pediatric oncology, Utrecht University, Leiden University, Solstice Pharmaceuticals B.V., CelluTx LLC USA, Anjarium Biosciences Switzerland, siTOOLs Biotech GmbH Germany, Lipoid GmbH Germany, Patiëntenvereniging Stofwisselingsziekten (VKS), Dutch Institute for Rational Use of Medicine (IVM), Karolinska Institute (Sweden), SINTEF (Norway), Val d’Hebron Hospital Spain, National University Singapore, European Technology Platform Nanomedicine (ETPN) (FR), Friedrich-Alexander- Universität Erlangen-Nürnberg (DE). Official secretary on behalf of the consortium: prof. dr. R.M. (Raymond) Schiffelers – UMC Utrecht

Large-Scale Neo-Cartilage Engineering: regenerative treatment technologies for osteoarthritis (LS-NeoCarE)
More than 1.5 million people in the Netherlands suffer from osteoarthritis – a degenerative joint disease. For many osteoarthritis patients, there is currently no treatment that can slow the disease process or cure it. Therefore, they struggle with pain and movement limitations every day. LS-NeoCarE wants to improve their lives by developing durable regenerative cartilage implants. These living implants are based on revolutionary stem cell, bioreactor, and 3D-printing technologies. Through the active involvement of researchers, industry, doctors, and patient organizations, the project creates support among both patients and doctors for applicability and with industry for marketing the developed implants.
Consortium: Eindhoven University of Technology, Leiden University Medical Center, UMC Utrecht, Utrecht University, Leiden University, Fontys University of Applied Sciences, University of Applied Sciences Utrecht, University of Applied Sciences Leiden, Regenerative Medicine Crossing Borders, Purac Biochem BV, Demcon, Scinus Cell Expansion BV, ASR Zorgverzekering, NC Biomatrix BV, Azar Innovations, Poietis France, Dutch Arthritis Foundation (ReumaNederland), patient participation arthritis Leiden LUMC (PPA-Leiden). Official secretary on behalf of the consortium: prof. dr. ir. K. (Keita) Ito – Eindhoven University of Technology

https://www.nwo.nl/en/researchprogrammes/dutch-research-agenda-nwa/research-along-routes-consortia-nwa-orc/awards-nwa-1

Criminal InvestigationDX - advanced diagnostics for criminal investigations based on innovative micro/nano technology
Official secretary on behalf of the consortium: dr. ir. M.L. Bennink (Saxion University of Applied Sciences)
Consortium: Saxion University of Applied Sciences, Ministry of Security and Justice, University of Twente, Wageningen University & Research, VU Amsterdam, Amsterdam UMC - location AMC, Nytor BV, Salvitat B.V., Beleef!Media, Benchmark, Center for Safety and Digitization (CVD), Public Prosecutor's Office (OM), National Police, Pervatech, Micronit BV, Novel-T, D Andrea&Evers.

To improve the efficiency and effectivity of tactical and forensic research, two novel innovative tools including working protocols are being developed, and implemented in the criminal justice system that empower the criminal investigator to rapidly acquire reliable information at the crime scene. The tools can determine whether a trace contains a sufficient amount of DNA for further analysis, or to extract more information from them, that can directly guide the investigation. Both tools will result in solving more cases in a shorter time, which directly contributes to the trust in criminal investigations and the sense of security of everybody.

HOLLAND HYBRID HEART, combining tissue engineering and soft robotics to build a biocompatible artificial heart that offers a future to heart failure patients
Official secretary on behalf of the consortium: prof. dr. J. Kluin (Erasmus MC)
Consortium: Erasmus MC, Eindhoven University of Technology, AMOLF, University of Twente, Saxion University of Applied Sciences Sustainable & Functional Textiles, Delft University of Technology, Maastricht University, Dutch Heart Foundation, Dutch Cardiovascular Alliance (DCVA), TrailBlazers, EE labels, Evos GmbH, Harteraad, Dutch Pulmonary Hypertension Association (PHA).
Worlwide, 23 million people suffer from heart failure. For advanced heart failure, heart transplantation is the gold standard. However, due to the limited availability of donor hearts, waiting lists are long and many patients die while on the waiting list. We are developing the Holland Hybrid Heart (HHH): the first functional artificial organ. The HHH is a soft robotic heart with an innerlining of the patient’s own cells. Together, the HHH resembles the healthy human heart as closely as possible. This safe alternative to a donor heart is essential to offer a lifesaving solution for thousands of heart failure patients.

https://www.nwo.nl/en/researchprogrammes/dutch-research-agenda-nwa/research-along-routes-by-consortia-nwa-orc/nwa-orc-2018-2022/awards/2022

LightUp – a pill-sized capsule endoscope for the early detection of esophageal cancer
prof. dr. J.F. de Boer (VU)
Each year, 600,000 people are diagnosed with esophageal cancer and 75% die within 5 years after their diagnosis. Screening with conventional endoscopy is offered to people with Barrett’s esophagus, a disease with a higher cancer risk, but it misses 25% of early cancer and is expensive. We developed the LightUp, a pill-sized imaging device that patients will be able to swallow. A nurse pulls the capsule up by a string and an AI algorithm will give a diagnosis. LightUp combines a technique that makes cancer tissue light up with high-resolution imaging. LightUp will detect at least 27% more early cancer.

ARTIC – Magnetic artificial cilia integrated modules enhancing life science applications
prof. dr. ir. Jaap den Toonder (TU/e)
Currently, 90% of drugs fail to pass clinical trials. Organ-on-a-chip (OoC) is an approach where microfluidic chips are used to test drugs on human tissues. OoC has proven to predict drug safety and efficacy better than animals and other traditional preclinical models. However, industry adoption of OoCs is still very limited. One main reason is that scientists have to choose between either a system with physiologically relevant flow but not fit for pharmaceutical procedures (e.g. automation, reliability, and reproducibility), or the other way around. To accelerate industry adoption of OoC, we introduce a new pumping technology that meets both criteria.

OPENOPTICS - Open Science for Optical Simulations
Dr. J.W.M. Beenakker (LUMC), with C. Haasjes (LUMC), L. van Vught (LUMC), M.J. Simpson (Freelance optical scientist, Texas, USA)
Ray-tracing is a widely used technique to study optical systems, such as a telescope or the eye. We have developed ZOSPy to automate these analyses and make them more accessible. Since we made ZOSPy available open-source, scientists from various disciplines are using it as a platform to share their methods and make them publicly available. In this project we will add features to ZOSPy that simplify this sharing of methods and results, together with a better documentation. This will allow ZOSPy to become a tool that stimulates the adoption of Open Science for optical simulations.

Evolving living cells from lifeless molecules
Main applicant: Prof. Dr. C (Cees) Dekker (TUD)
Coapplicants: Prof. Dr. G.H. (Gijsje) Koenderink (TUD), Dr. K (Kristina) Ganzinger (AMOLF), Prof. dr. S.J. (Siewert-Jan) Marrink (RUG), Prof. dr. M. (Marileen) Dogterom (TUD), Prof. dr. T.S. (Wilhelm) Huck (RU), Prof. dr. M.J. (Jeroen) van den Hoven (TUD)
What is life? To address this longstanding question, EVOLF will use lifeless biomolecules to build a living synthetic cell that has the attributes of living systems: autonomous growth, self-replication, communication, and evolution. To realize and integrate these complex cell functions, we will use laboratory evolution aided by artificial intelligence. In parallel, we will articulate ethical guidelines for responsible human control of synthetic life. Building a synthetic cell will yield an unprecedented deep understanding of biological life.

Visualising metazoan replication initiation with correlative fluorescence and cryo-electron microscopy
Dr. D.F. Ramirez Montero -> Delft University of Technology -> United Kingdom -> The Francis Crick Institute -> 24 months
Before dividing, cells need to make an exact replica of their DNA to ensure that each daughter cell obtains a copy. Mistakes in this process can be fatal and cause several genetic diseases. This study aims to understand how cells start this DNA copying process, a critical stage that is defective in many diseases.

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Breaking Barriers in Cardiac Regeneration: Harnessing Cardiac Stem Cell Mechanobiology and Hydrogel Building Blocks for Next-Generation Therapies
Dr. ir. D. Mostert (TU/e -> DWI-Leibniz-Institut für Interaktive Materialien (DE)).
This research aims to improve recovery after a heart attack by using advanced hydrogels and heart cells derived from stem cells. These hydrogels and cells work together to restore heart tissue structure, laying the groundwork for enhancing heart function and preventing heart failure.

Uncovering the universal mechanism to bacterial mutagenesis and antibiotic resistance
Dr. M. Tišma (TUD -> Harvard University (US))
Antibiotic resistance presents a rapidly growing public health crisis today. Bacteria evade the antibiotics by rapidly mutating and altering their DNA. This project will focus on understanding a central mechanism that promotes mutations necessary for antibiotic resistance. This research provides a key target for preventing bacteria to gain antibiotic resistance.

Optimizing Teixobactin: Minimizing Nephrotoxicity through Megalin-Directed Strategies
Markus Weingarth (UU)
Consortium: Nathaniel Martin (LEI), Dallas Hughes (Novobiotic Pharmaceuticals/Cambridge), Ron Byron (Cell4Pharma), Roos Masereeuw (UU), Kim Lewis (Northeastern University)
There is an urgent need for the development of new antibiotics. Clinically useful antibiotics need to be effective and safe. However, while the molecular rules of antibiotic effectivity are increasingly better understood, not much is known about how to make antibiotics safer. Especially the kidney, which serves as a filter of the human body, can be damaged by unsafe, so-called nephrotoxic antibiotics. In our project, a consortium of two academic and two industrial collaborators will combine structural biology, medicinal chemistry, nephrotoxicity expertise, and drug development expertise to design improved antibiotics that are less toxic to the human kidney.

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Demand by Consortia – S Read more >

Future Optical Broadband Systems research programme Read more >

Next generation detectors and light sources for imaging and spectroscopy (NextDeLights)
Jeroen Kalkman (TUD)
Co-applicants: Steven van den Berg (HHS), Arjan Lock (HHS), Joke Korevaar (HHS), Renate van den Bos (Erasmus MC)
In this project, researchers will work together with industry to improve light sources and detectors for the development of new devices for spectral and optical coherence tomography imaging. The developed devices will be applied in the agro-food, semiconductor and in particular to healthcare, where they will contribute to, respectively, improving food yield, better quality control, and early skin cancer detection and diagnosis.

Chiral symmetry breaking by self-assembly
Sijbren Otto (RUG)
Most molecules can exist in two forms that are each other's mirror images. Current life mostly uses only one of these. It remains a mystery how this preference emerged. The researchers will address this question by investigating a recently discovered system in which a preference for one of the mirror images emerges spontaneously.

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Enhanced ssNMR for Nano-materials, Surfaces and Non-Equilibrium Processes (NaSuNe-ssNMR): Visualizing (bio)materials and their motions with enhanced molecular MRI scans
Main applicant: Prof. Dr. Patrick van der Wel (RUG)
This new research infrastructure will enable researchers to understand how (smart) materials and biological processes behave and function on the molecular level. Combining light and microwaves together with a form of molecular MRI scanning allows for new insights of how molecules move and interact. A central focus is on seeing processes on surfaces of materials, such as catalysts and solar panel materials. These new abilities will be deployed in studies of molecular machines, ‘green’ materials, drug carriers, and ageing-associated diseases.

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Cryogenic-soft landing imaging mass spectrometry: an ultrapure biological sample preparation platform for cryogenic-electron microscopy
Dr. A. Mathew (UM), Prof. dr. R.M.A. Heeren (MU), Amsterdam Scientific Instruments, DEMCON, Thermofisher Scientific, VitroTEM
Macromolecular assemblies (MMAs), such as protein complexes and viruses, play a crucial role in biological processes such as signal transduction and cellular transport. Understanding their molecular structure is essential for insights into human health. Cryogenic electron microscopy (cryo-EM) is a powerful tool for determining the atomic structure of MMAs. However, several challenges related to sample preparation, data collection and processing, electron beam damage and instrument limitations, hinder further progress in spatial resolution. The project focuses on image-guided native mass spectrometry (nMS) as a tool for sample preparation for cryo-EM.

PRISTINE: PReclinical validation of multi-modal Imaging Systems and Technologies In NEuromuscular disorders
Prof. dr. ir. T.W.J. Scheenen (RUMC), Prof. dr. N. van Alfen, (RUMC), dr. J.C. de Greef (LUMC), prof. dr. ir. N.J.J. Verdonschot (UT), iThera Medical, Solve FSHD
Muscle diseases have a huge impact, not only on patients, but also on their families and those closest to them. These conditions limit daily functioning, lead to reduced quality of life and cause both emotional and physical stress. This project aims to improve healthcare and the lifespan of individuals living with a muscle disease through the development of advanced multimodal imaging. A comprehensive preclinical muscle imaging tool is being developed. The multimodal imaging protocol will provide robust assessment of muscle contractility and tissue quality to characterise the changes in muscle health observed in the FLExDUX4 mouse model of facioscapulohumeral muscular dystrophy (FSHD).

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Open Technology Programme Read more >

Degrading gradients
Ruud Weusthuis (WUR)
Co-applicant(s): Mark Bisschops (WUR), Max Fürst (RUG), Cees Haringa (TUD)
Sugar and oxygen gradients frequently occur in industrial-scale bioreactors and commonly have a detrimental effect on yield, productivity, and product quality. Reducing or even preventing the occurrence of these gradients is therefore of eminent importance but attempts to realize this by improving the bioreactors have so far only been partially successful. We are proposing a completely new approach to solve this challenge by changing the microorganisms, not the bioreactor.

Veni

2021

2022

2023

2024

Vidi

2021

2022

2023

Vici

Open Competition XS

2023/2024

2024/2025

Open Competition M

2023/2024

2024/2025

Open Competition XL

Gravitation

ORC

Take off

Open Science fund

Summit grant

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KIC

NWA – Innovation and Networks

Infrastructure – Research infrastructure National Consortia

HTSM

NWO Domain Applied and Engineering Sciences