The summaries of the approved projects are listed below in alphabetical order:
Running on fumes: modelling the loss of metabolic flexibility in the failing heart
Dr. M.E. Adriaens (Maastricht University)
When heart failure occurs, our heart loses its ability to use a wide variety of nutrients for energy production. This loss of metabolic flexibility appears to worsen with disease progression, but it is not clear which metabolic processes are affected nor how these changes differ between men and women. In this project, I will develop a systems biology approach to study the loss of metabolic flexibility during heart failure in detail. In doing so, I aim to shed some much-needed light on a complex symptom of a deadly disease.
Beyond graphene: hydrogen fuel generation via borophene-based sustainable chemistry
Dr. I. Amin (Universiteit van Amsterdam)
Hydrogen is suggested as the future fuel, replacing fossil-based fuels. Hydrogen storage should be safe, easy, reversible, have a high gravimetric/volumetric capacity. This makes chemical hydrogen storage promising. To generate hydrogen from them, we need to develop suitable catalysts. Herein, we propose to use Borophene, a new emerging 2D material, as catalyst to generate hydrogen. Theoretically, Borophene outperforms other 2D materials, even Graphene, in generating hydrogen. Our work will be performed in a sustainable way, following concept that would generate energy with greener process and product. Our work will benefit storage and distribution of the hydrogen and thus the society.
Next generation 3D-printed separation membranes
Dr. H. Bazyar (TU Delft)
Current membrane fabrication processes are not sustainable as they are energy-intensive and require hazardous solvents. A new green method for membrane fabrication is 3D printing which eliminates extra fabrication steps, decreases waste production and CO2 emissions. Also, more control is provided on the design, shape and type of membranes. In this proposal I study the possibility of fabricating 3D-printed porous membranes with well-defined nano/micro-scale pore size, location and geometry. The proposed method can revolutionize membrane fabrication procedures leading to the development of novel membranes with high permeability and selectivity. The fabricated ultra/microfiltration membranes will be used for wastewater treatment applications.
Feeding on light: genetic mechanisms of photosymbiosis in a highly regenerative animal
Prof. dr. E. Berezikov (UMC Groningen)
Can animals substitute food with sunlight? Yes, if they form a symbiotic relation with an organism that has photosynthesis. This form of symbiosis, called photosymbiosis, is in fact widespread and present in diverse species, from sponges and corals to even some vertebrates. Photosymbiosis plays a key role in ocean ecology. Biomedical applications of photosymbiosis are also under active development and hold a great promise. However, very little is known about the genetic mechanisms required for the establishment of photosymbiosis. We propose to bridge this knowledge gap using a remarkable novel model organism, a photosymbiotic acoel worm Symsagittifera roscoffensis.
Finding new ways to kill pathogenic fungi
Dr. S. Billerbeck (Rijksuniversiteit Groningen)
Fungal pathogens pose a threat to human health and food security. Very few antifungals are available, and resistance to these is rising. There is an urgent need for new antifungals that feature new modes of killing action. Yeasts – such as our common baker’s yeast and related species – have evolved a large set of functionally diverse toxic proteins to compete against fungi in the environment. The researchers will develop a workflow that can reveal how these toxins kill pathogenic fungi and how different their killing strategies are. This knowledge could be used to develop new antifungals with diverse modes of action.
MechanoPore – Programmable, shape-shifting DNA origami nanovalves for size-selective delivery of biomolecules across cell membranes
Dr S. Caneva (TU Delft)
Protein nanopores are the gatekeepers of the cell. They are narrow, fixed channels through which ions and small molecules are selectively transported. Macromolecules, however, are too large to shuttle into cells through these nanochannels. With MechanoPore, we will pioneer the first mechanically-adaptable nanopores by uniquely combining DNA origami nanotechnology, machine-inspired design and synthetic biology. Our innovative approach will answer fundamental biophysics questions regarding the i) dynamics of the shape change, ii) the force balance at the membrane/nanopore interface and iii) the design of a fast and programmable trigger mechanism, opening up an entirely new direction in the nanopore field.
All immune-defence mechanisms are balanced: fact or fiction? Truth-finding in cancer patients.
Dr. G. Flórez Grau (Radboud UMC)
Cancer patients often suffer from other diseases like infections. A scientific explanation is that tumour cells secrete factors that modulate the immune mechanisms in their own favour, hence facilitating their own survival. Here, I postulate that the presence of tumour cells even impedes the development of trained immunity, a state in which the immune system can react very fast to intruders due to previous stimulation. If this immune-inhibiting form of trained-immunity exists this project uncovers a whole new scientific field. Reversing this inhibitory state will facilitate the development of beneficial trained immunity types of immunotherapies for the benefit of patients
A novel technology for long-term mapping of memory representations in the brain
Dr. K. Gulmez-Karaca (Radboud UMC)
Memories are highly dynamic and can be updated, forgotten or transformed with the passing of time. In the brain, memories are represented by alterations in the connections between activated neurons. The investigation of these time-dependent changes in memories at the level of their neural representation therefore requires long-term mapping of neuronal connectivity. So far this was not possible. This project will develop a new technique to capture the neuronal connectivity footprints of specific memories in the brain, enabling the investigation of the dynamic nature of memory representations over time.
HIV latency: short-term decisions with long-term effects
Dr M.M.K. Hansen (Radboud Universiteit)
Human immunodeficiency virus (HIV) is the virus responsible for AIDS, for which there is still no cure. HIV infected cells can be found in two states: actively replicating, where HIV is killing patients’ immune cells as it spreads; or in a dormant state–– termed latency––where HIV is quietly hiding and cannot be targeted by drug treatment. HIV latency is the major barrier to an HIV cure. In this project, we will study how HIV remains dormant and hides within human cells with the ultimate goal of devising a new strategy to minimize the latent HIV population within patients.
Nanocarriers for Proteolysis Targeting Chimeras to Fight Incurable Diseases
Dr. M.A. Hempenius (Universiteit Twente)
Alzheimer, cardiovascular disease, chemotherapy-resistant cancers- all these conditions remain incurable. We will develop tiny particles, nanocarriers, for treatment of such conditions. Our unique approach is to encapsulate Proteolysis Targeting Chimeras (PROTACs) in nanocarriers. PROTACs are novel, revolutionary drugs that degrade “bad” proteins involved in these conditions. PROTACs were efficient in initial experiments. However, major challenges hamper PROTACs performance: stabilization of PROTACs in blood, and targeting the diseased cells. Encapsulation of PROTACs in nanocarriers will tackle these challenges, leading to new treatments of major public health problems in the future.
Testing the ‘Stagnant Mantle’ Hypothesis: Finding geological fingerprints of ancient plate subduction in young Pacific volcanoes
Dr. D.J.J. van Hinsbergen (Universiteit Utrecht)
Geology textbooks show a vigorously convecting mantle below tectonic plates, but recent geological and geophysical observations suggest the opposite: a stagnant mantle that only flows where disturbed by plates. Paleogeographic reconstructions show that >150-million-year-old volcanoes of Vancouver Island (Canada) formed due to subduction at the location of the active Revillagigedo volcanoes, 1000 km west of Mexico, now far away from a subduction zone. The researchers will test if the Revillagigedo volcanoes contain geochemical fingerprints of subduction and minerals with ages comparable to the Vancouver Island volcanoes. If true, this will have major impact on understanding earthquakes, volcanism, and natural resources.
Detecting Multiple Sclerosis via breath analysis using an electronic Nose
Prof. dr. F.J.P.M. Huygen (Erasmus MC)
We will investigate whether an eNose can detect Multiple Sclerosis (MS) and monitor the disease’s progression. There is not yet a quick test nor a non-invasive method to identify patients with MS or distinguish between various types of MS. An electronic Nose is a diagnostic device to detect patterns in the compounds that are exhaled by patients. The disease-specific metabolic pathways give rise to specific compound-patterns in exhaled breath that aid in detecting diseases. Exhaled breath data and clinical parameters will be used to develop a predictive model to detect and monitor MS, based on supervised machine learning techniques.
Elucidating enzymatic dark matter
Dr. R.S. Jansen (Radboud Universiteit)
Despite extensive efforts, even the best-characterized organisms still contain numerous uncharacterized proteins predicted to be enzymes. Enzymes convert one molecule into another and are essential for life. This enzymatic dark matter greatly obscures our understanding of life at the molecular level but elucidating it will take decades at the current pace. This project aims to dramatically increase the speed of enzyme annotation by developing an innovative method that links all enzyme activities in a cell to its proteins. The approach can be applied to any organism and has the potential to revolutionize the field of biochemistry.
Building a minimal cell cycle clock in the test tube
Dr. J.L. Kamenz (Rijksuniversiteit Groningen)
Cell division is a fundamental process that is the basis of all uni- and multicellular life. At its core, the cycle of cell growth and cell division is thought to be driven by a negative feedback loop consisting of only a handful of proteins. We aim to assemble this central cell cycle clock from its individual parts taking a systematic bioengineering approach. If we succeed, we will gain new insights into this important process, if we fail it will lay open current gaps in our knowledge.
CHitosan Interacts with Polyphenols & Digestible Acorn proteins are Left in solution
Dr. ir. S. Lindhoud (Universiteit Twente)
To feed the world sustainable protein sources have to be found. Plants would be an ideal protein source, but protein recovery from plants has been proven difficult due to the interactions between proteins and polyphenols. In CHIP&DALE an environmentally friendly water-based method will be developed to separate polyphenols and proteins from acorns. This separation method is inspired by the way molecules are spatial temporal organised in the cellular fluids. If our recovery method is successful it can be applied to other seeds, peels and plant waste material, uncovering new sustainable protein sources to feed the planet.
Size distribution of nanoplastics in indoor, urban and rural air
Dr. D. Materic (Universiteit Utrecht)
Air quality in urban areas is a topical public health concern; it has been reported that aerosol concentration in the air significantly affects human health, decreasing life expectancy by up to 5 years. Plastic aerosol pollution is recognised as an emerging global problem, as microplastics have been found to be globally pervasive. Smaller plastic particles have an even greater toxicological importance, so in this project, we will focus on nanoplastics (size <1 μm) We suggest a novel experiment to measure the different types and size-distributions of the nanoplastics in indoor, urban and rural air.
Making Specialty Chemicals and Pharmaceuticals from Wastewater
Dr. J.B. Mensah (Universiteit Utrecht)
In our current linear economy, resources are inevitably lost as waste. In contrast, in a circular society, waste is a resource, e.g., for renewable carbon to produce essential chemicals. Research aimed at recovering and upgrading this carbon to value-added chemicals sustainably, i.e., with efficient and clean conversion processes, is still in its infancy. Here, we aim to develop a novel strategy that enables the direct catalytic transformation of wastewater-sourced carbon feedstock into valuable chemical building blocks for specialty chemicals and pharmaceuticals. If successful, this work will enable new environmentally friendly manufacturing processes using waste as circular feedstock.
Microbially-produced lipids as a sustainable alternative to palm oil
Dr. R.A. Ohm (Universiteit Utrecht)
Palm oil is an important ingredient of food and biofuel. However, oil palm trees are mostly grown in tropical areas, resulting in the clearance of large swaths of rainforests. Microbially-produced lipids are an attractive sustainable alternative. The singlecelled yeast Cutaneotrichosporon oleaginosus produces high amounts of lipids, but only under specific growth conditions. The aim of this project is to understand the genetic regulation of lipid accumulation. Eventually, this knowledge may result in strains that produce lipids under all growth conditions, considerably increasing the economic viability of microbial lipids as a sustainable alternative to palm oil.
Mosquito RNA vaccine (MORV)
Dr. ir. G.P. Pijlman (Wageningen University & Research)
Vaccination of humans is not always possible for viral diseases transmitted by blood-feeding mosquitoes. This proposal is a proof-of-concept to ‘vaccinate’ mosquitoes using a self-replicating mosquito RNA vaccine (MORV). The MORV is a small synthetic RNA that can be rapidly tailored to any viral disease. This short project will engineer the MORV, study the mosquito immune response, and test if mosquitoes become resistant to Zika and West Nile virus. Eventually, MORV-vaccinated mosquitoes can be released into the environment to reduce virus transmission. The project is also important to establish the legal status of novel genomic techniques in renewed European legislation.
From methanol to medicine – Sustainable microbial production of polyketide antibiotics
Dr. L. Schada von Borzyskowski (Universiteit Leiden)
Polyketide antibiotics, such as erythromycin or tetracycline, are vital in treating infectious diseases. However, their current production by Streptomyces bacteria is complex, expensive and unsustainable. Therefore, alternative production methods are urgently needed. Here, an innovative concept for the sustainable microbial production of polyketide antibiotics from the inexpensive compound methanol is proposed. Antibiotic-producing enzymes from Streptomyces will be transferred to Methylorubrum extorquens, a bacterium growing efficiently on methanol. Since these enzymes are complex molecular machines, their transfer into another microorganism is highly challenging. Antibiotic production from methanol represents a ground-breaking achievement and opens up a new research field.
Aurora in a flask: liquid-phase plasma reactors for sustainable production of chemicals and fuels
Dr. N.R. Shiju (Universiteit van Amsterdam)
Traditionally, chemical reactions are done in thermally heated reactors. The plasma reactors are being developed as alternative for gas-phase reactions, but not for liquid-phase. We will develop a novel, inexpensive plasma-in-liquid reactor to conduct chemical reactions in liquid-phase at low temperature and pressure. The plasma-in-liquid will produce energetic species which will react with the liquid reactants and convert them into value-added products. No external reactor heating will be necessary, an advantage for temperature sensitive biomass conversions. Since the plasma can be generated with renewable electricity, and the reactor system is scalable, this will lead to a sustainable electricity-based chemical industry.
DNA Metabarcoding might illuminate plant-pollinator networks
Dr. K.B. Trimbos (Universiteit Leiden)
Pollinators are crucial for ecosystem functioning and food production. Understanding which pollinators are associated with which plants (plant-pollinator networks) and how these interactions change across time and space is of critical importance, especially given the current pace of human-induced environmental change. Our current understanding is limited to visual observations, which are extremely time-consuming, labour intensive and biased against rare species. This project aims to test the possibility and accuracy of using pollinator DNA extracted directly from flowers as a new method. If successful, this will revolutionize our understanding of plant-pollinator networks through a more efficient and accurate assessment.
Assessing mobilized cancer stem cells in bile for diagnosis of cholangiocarcinoma and drug-sensitivity screening.
Dr. ing. M.M.A. Verstegen (Erasmus MC)
Bile duct cancer (cholangiocarcinoma) is an aggressive malignancy for which early diagnosis remains challenging. Reliable biomarkers accurately predicting tumour progression or therapy responsiveness are unavailable. Therefore, better diagnostic methods are urgently needed. We hypothesize that tumour cells shed into bile, can be isolated allowing early diagnosis and drug-sensitivity testing in vitro. We will assess if these shed tumour cells can be detected in patient bile samples and confirm tumorigenicity by passing these cells (expanded in organoids) through a bile duct-on-a-chip, mimicking the natural bile duct environment. This provides detailed monitoring of tumour invasion in vitro and allows effective drug-response measurements.
Sustainable Forest Protection: Biobased Nanocarriers Against the Bark Beetle
Dr. F.R. Wurm (Universiteit Twente)
The bark beetle is a major threat to forests worldwide, destroying this natural protection of our climate. Even worse, climate change lets the bark beet population grow rapidly. Thus, this pest can destroy larger quantities of forests. The only weapons to date are massive spraying of pesticides and cutting the infected trees. We propose a sustainable alternative using drug-loaded sugar- or lignin-based nanocarriers. These nanocarriers are injected inside of the trunk of infected trees, transported to the place of the beetle or their larvae, and attack them as a nanosized Trojan horse - without spraying of pesticides.
Air-water flow properties in highly unsteady flows
Dr. ir. D. Wüthrich (TU Delft)
In a world strongly influenced by climate change and sea-level rise, natural hazards in the form of highly unsteady flows represent an increasingly worrying threat. The large air entrainment involved in these phenomena’s physical behaviour remains mostly unknown. For this, I introduce a new methodology to investigate the air-water flow properties in breaking bores using an array of dual tip phase-detection probes. This method will lead to a reliable estimation of air-water characteristics and turbulent properties in highly unsteady flows, providing new and useful insights on the working mechanism of water-related extreme events.
Firefly: Communicating, Navigating and Localizing Drones Solely With Light
Dr. M.A. Zuñiga Zamalloa (TU Delft)
Drones are not fully trusted yet. Their reliance on radios and cameras for navigation raises safety and privacy concerns. These systems can fail, causing accidents, or be misused for unconsented recordings. Considering recent regulations allowing commercial drones to operate only at night, we propose a radically new infrastructure where drones obtain communication and navigation solely from the light bulbs in our streets, roads and buildings. Modulated light intensity will allow drones to operate outdoors and indoors without the need for radios, GPS or cameras. Firefly will transform our vast lighting infrastructure into the backbone for drone operation.
