Over €6 million for innovative and urgent research via Domain Science-KLEIN

3 October 2019

The Board of NWO Domain Science has awarded 18 applications in the NWO Open Competition Domain Science - KLEIN. The topics involved vary from the study of DNA repair to research that focuses on the interaction between time and memory in a quantum computer. KLEIN (or ‘small scale’) grants are intended for innovative, high-quality, fundamental research and/or studies involving matters of scientific urgency.

Distribution of KLEIN grants

There are three categories of KLEIN grants: KLEIN-1 (one scientific position), KLEIN-2 (two cooperating scientific positions) and KLEIN-0 (investments). In this second KLEIN round, a total of 60 applications were processed, 37 of which were KLEIN-1, 13 were KLEIN-2, 1 was KLEIN-0 and 9 were KLEIN-1 applications with preferential treatment. The board decided to approve the 17 highest ranked applications and one additional application through the preferential treatment scheme. In total, NWO Domain Science has approved 2 KLEIN-2 applications and 16 KLEIN-1 applications, of which 5 requested preferential treatment. The board instituted the preferential treatment scheme to simplify the process through which researchers who are just starting out on their career can acquire funding.

The following applications have been approved (in alphabetical order, by author):

Targeting the neurons that drive overconsumption in obesity
Prof. R.A.H. Adan (Utrecht University)
Among the specific populations of neurons that stimulate eating behaviour, we have yet to identify those which play a role in over-consumption in obesity. In this project we focus on neurons in the lateral hypothalamus, an area of the brain involved in eating control. We study how these neurons change in obesity and whether manipulation of these neurons can prevent you from becoming overweight when exposed to an environment rich in food that is high in fat and sugar. Such insights are needed for the development of new strategies to treat obesity.

Stem cell differentiation programs in the regenerative flatworm Macrostomum lignano
Prof. E. Berezikov (University of Groningen)
New cells are formed by the differentiation of stem cells into specialized cells. Our understanding of the regulatory processes underlying this differentiation is still insufficient. The flatworm Macrostomum lignano provides a suitable model for studying this process due to the ongoing occurrence of differentiation during homeostasis and regeneration. The creature’s transparent body enables us to engineer transgenic worms with the aim of visualizing specific cell types using a fluorescent colour. These cells can also be isolated and characterised in detail. By focusing on cells that represent successive steps of differentiation, we can further our understanding of how this process is regulated.

Keeping the peace at the mucosal surface. How does host immunity control bad bugs?
Dr S. Brugman (Wageningen University & Research)
Intestinal bacteria are important to our health. Disruptions in the composition of our intestinal bacteria can lead to chronic conditions such as inflammatory bowel disease. When the immune system is not working properly, certain bacteria (pathobionts) can increase in number and cause illness. This study focuses on such processes in zebrafish. The cells of the immune system and intestinal bacteria can be readily controlled in these fish, enabling scientists to identify and analyse the mechanisms which play a role in controlling ‘bad’ bacteria. Once we understand how the immune system controls these pathobionts, we can use this knowledge to restore balance to the disrupted composition without having to resort to antibiotics.

Accurate gas dynamics of distant galaxies: resolving the controversies
Prof. F. Fraternali (University of Groningen)
The universe contains billions of galaxies such as our Milky Way; how these galaxies originated is still unclear. What is the role played by 'dark matter', matter that cannot be directly observed? As part of this research, new telescopes are being used with the capacity to observe galaxies at vast distances. The greater the distance, the earlier these systems were formed in the history of the universe. By studying the flow of gas in younger and older galaxies using a new, high-precision technique developed in my research group, the amount of dark matter at different developmental stages in galaxies can be clearly inferred.

Macrocyclic inhibitors of protein-protein interactions combining peptidic and small-molecular fragments
Dr S. Hennig (Vrije Universiteit Amsterdam)
Proteins play an important role in the cells of every organism. They form part of a complex network of protein interactions which, if out of balance, can result in neurodegenerative diseases or various forms of cancer. Modulators of protein interactions are essential for resolving these types of imbalances and can lead to the development of new drugs. In this project, I will combine the power of traditional, chemically active substances with the benefits of protein-inspired peptide molecules. This will generate chimeric compounds capable of tackling biological targets that have to date been inaccessible.

Cleaving like a Pro: PPEP (Pro-Pro endopeptidase)-regulated processes in Clostridiodes difficile
Dr P.J. Hensbergen (Leiden University Medical Center)
Clostridioides difficile, a bacterium that causes intestinal infections, secretes an enzyme (PPEP-1) that regulates the spread of the bacterium. In doing so it cleaves surface proteins from the bacteria, proteins which are necessary for attachment. However, in the case of one of these surface proteins, we have yet to discover what it attaches to. PPEPs also occur in other bacteria, but their activity is slightly different. C. difficile also has a second PPEP, but its function is unknown. In this project we want to further unpack the PPEP-regulated processes in C. difficile, and to better understand the activity of different PPEPs.

Temporal control of chromatin factor binding during in vivo cell differentiation
Prof. S.J.L. van den Heuvel (Utrecht University)
In human and animal development, most body cells stop dividing and fully specialise. The cessation of cell division associated with differentiation is essential for forming tissues and organs, and prevents cancer from developing (tumour suppression). The molecular mechanisms responsible for this coupling are not yet understood within living systems. The research described will use a simple animal model to explore how key tumour suppressor proteins switch off cell division while stimulating differentiation. It will also determine when and where these proteins bind to DNA, and how this regulates cell division.

The MAP7 family – understanding the MAPs for neuronal transport
Prof. C.C. Hoogenraad (Utrecht University)
The human brain consists of billions of interconnected nerve cells. These cells use specialised extensions called dendrites to send signals to or receive signals from one another. All of the components needed to perform these specialised tasks are transported in these dendrites by small motors running over a network of microtubules; the information highways of the cell. This transport is further regulated by proteins that bind to the microtubules and affect the motors. In this study, we will investigate how MAP7 proteins stimulate the transport in nerve cells and how this process contributes to nerve-cell development.

Quantum time-space tradeoff lower bounds
Dr S. Jeffery (Centrum Wiskunde & Informatica)
In order to make the fullest possible use of quantum computers, we need to understand both their capabilities and their limits. We know how much time a quantum computer takes to solve many types of problems, but the fastest methods use a lot of memory while the methods that use the least memory are very time-consuming. Is it possible to find algorithms that combine optimum speed with optimum memory use, or will a compromise always be inevitable? Researchers will develop new techniques to gain insight into the interaction between time and memory required for a quantum computer to solve computational problems.

Seminal fluid dynamics: embracing variation from individuals to species
Dr J.M. Koene (Vrije Universiteit Amsterdam)
In addition to sperm, an ejaculate contains a complex composition of substances, the main ones being seminal fluid peptides. These proteins can bring about dramatic changes, such as stimulating egg-laying or inhibiting mating with other partners. These are among the fastest evolving proteins and our goal is to identify the underlying reason for this rapid evolution. We use hermaphrodites to investigate this, as they provide the only way to distinguish between competing hypotheses. By mapping genome, transcriptome and proteome diversity within and between species, we can answer this question at both micro-evolutionary and macro-evolutionary level, and also identify new options for reproduction control.

State estimation for spatio-temporal point processes with applications to criminology.
Prof. M.N.M. van Lieshout (Centrum Wiskunde & Informatica)
In information-driven police work, attempts are made to predict where and when crimes such as burglaries may occur with a view to possible intervention. This calls for reliable mathematical models. The ETAS model used in California leads the way in this area, defining a point process in time and space with a stochastic intensity that combines neighbourhood-related information with a clustering of crime over time (the 'contamination' or 'near repeat' effect). Police reports are used as a basis for estimating the model's parameters, generating a risk map that shows where and when there is an increased risk which necessitates the deployment of additional police capacity. Such estimates are often complicated by the fact that the exact time of a burglary is often unknown, for example if it occurs while the residents are on holiday. It is also interesting to know which crimes have been committed by the same perpetrators. This kind of unobservable information is referred to as latent. The aim of our research proposal is to reconstruct such latent information on the basis of observations and to use it to improve the model’s predictions.

Deciphering the biochemical basis of transcription-coupled DNA repair
Dr M.S. Luijsterburg (Leiden University Medical Center)
Protein machines that read DNA code can collide head on with damage in the DNA. This damage is cleaned up through the coordinated structure of DNA repair machines. The researchers use a combination of advanced genetic and biochemical analyses to study how these repair machines are constructed and go about their task.

Towards a mathematical theory of functions of random distributions
Dr W.M. Ruszel/ Dr A. Cipriani (TU Delft/TU Delft)
Universality classes are used in the natural sciences to classify various models for microscopic behaviour according to their macroscopic behaviour. One aim of this proposal is to identify new classes for generalized stochastic distributions. These objects are very irregular. Even so, they can be studied using a constructive approach involving discrete grid models, after which we allow the grid discretization distance to reach zero. In addition to models in Euclidean spaces, we also study models in compact Riemannian varieties. Our construction also has implications for the study of stochastic partial differential equations and logarithmic conformal field theory.

Where do we lose potential in perovskite solar cells?
Dr T.J. Savenije/ Dr B. Ehrler (TU Delft/AMOLF)
Solar cells are an essential component of the transition to a renewable energy supply. The efficiency of perovskite solar cells has increased enormously in recent years and is now comparable to that of existing technologies, such as multicrystalline silicon. In this project we will develop a special kind of perovskite solar cell with the electrical contacts on one side using microscopic, optical and electrical techniques to identify the loss mechanisms. We will then develop methods to eliminate these losses with the ultimate aim of further improving the efficiency of perovskite solar cells.

Packaging and accessing DNA molecules
Prof. H. Schiessel (Leiden University)
Our DNA molecules are packaged by proteins in compact structures. The aim of this project is to understand how modern gene editing techniques nevertheless get access to their target in the DNA.

Backward Lagrangian Tracking of the Patchiness of Oceanic Nutrients in a Turbulent Ocean
Dr E. van Sebille (Utrecht University)
Phytoplankton is the basis of ocean life and absorbs CO2 from the atmosphere, mitigating the effects of climate change. Phytoplankton needs light and nutrients in order to grow. The source of these nutrients is unknown, however, making it almost impossible to gauge the sensitivity of phytoplankton growth to changes in the ocean. With this in mind, oceanographers are planning to simulate how ocean currents transport nutrients. They will do this by implementing for the first time an advanced mathematical technique to simulate turbulence in an ocean model. This will enable them to understand how small-scale variations in quantities of nutrients lead to complex patterns in the distribution of phytoplankton.

Molecular drivers of extracellular vesicle-mediated intercellular RNA transfer
Dr P. Vader (University Medical Center Utrecht)
Cells in the human body exchange information, including genetic material, through small membrane vesicles. These vesicles fulfil important functions in the healthy human body, but can also contribute to the progression of diseases such as cancer. This project investigates how the vesicles deliver their genetic material to other cells and which vesicle surface proteins are involved in this process.

Synchronized, stochastic transcription factor dynamics during insulin-mediated stress response in C. elegans.
Dr J.S. van Zon (AMOLF)
When living organisms are exposed to stress, they have to activate the right genes to survive. In the nematode worm C. elegans , the insulin-signalling network regulates the response to very different types of stress, such as high temperature or a lack of food. We use advanced microscopy to understand why one protein in this signalling network, DAF-16/FoxO1, randomly oscillates under constant stress between the cytoplasm and the cell nucleus, where it switches on stress-specific genes. Our aim is to investigate whether the dynamics of these oscillations provide information on the level and type of stress, and on the mechanism that synchronizes these oscillations so strongly within the body.

About the NWO Open Competition Domain Science – KLEIN

KLEIN grants are intended for realising curiosity-driven, fundamental research of high quality and/or scientific urgency. The KLEIN grant offers researchers the possibility to elaborate creative and risky ideas and to realise scientific innovations that can form the basis for the research themes of the future. There are three categories of KLEIN grants: KLEIN-1 (1 scientific position), KLEIN-2 (2 scientific positions in collaboration) and KLEIN-0 (investments) that are assessed in competition with each other. A preferential treatment scheme is available to make it easier for researchers who are just starting out on their career (new permanent members of staff and tenure trackers) to acquire funding. This only applies to KLEIN-1 applications.

You can submit applications to NWO Open Competition Domain Science - KLEIN at any time.

Contact

For more information about NWO Open Competition Domain Science - KLEIN, please contact Margot Snel, enw-klein@nwo.nl, +31-(0)70 344 07 58.

Source: NWO