Sixteen innovative research projects launched through Domain Science-KLEIN

16 April 2020

The Board of the NWO Domain Science has awarded sixteen applications in the Open Competition Domain Science - KLEIN.

The topics range from research into mathematical models that can support the treatment of metastatic cancer, to exploring how better quality control in cells can prevent people from developing Parkinson’s disease. KLEIN grants are intended for innovative, high-quality, fundamental research and/or studies involving matters of scientific urgency.

How funds are distributed between KLEIN-1, KLEIN-2 and KLEIN-0

In this fifth KLEIN round, a total of 60 applications were evaluated, 27 of which were KLEIN-1, 14 were KLEIN-2, 2 were KLEIN-0 and 17 were KLEIN-1 applications with preferential treatment. The Board of the NWO Domain Science decided to approve the 13 highest priority applications and 3 additional applications through the preferential treatment scheme. In total, the Board has approved 4 KLEIN-2 applications and 12 KLEIN-1 applications, of which 6 with requested preferential treatment. The Board instituted the preferential treatment scheme to simplify the acquisition of funding for starting researchers.

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

 

The Antarctic Ice Sheet during the Last Interglacial: what does it really tell us about the ice sheet’s future?
Dr Pepijn Bakker (Vrije Universiteit Amsterdam)
During the Eemian (~130,000 years ago), global temperatures were 0.5-1°C higher than at present and global sea level was 6-9 m higher, due – to some extent – to the partial melting of the Antarctic Ice Sheet. This period is often presented as a picture of our future climate, in which similar conditions are expected to prevail. This project will involve a large number of Earth System model experiments, which will be compared to geological data, to clarify what really happened to the Antarctic Ice Sheet during the Eemian. If we can find out what actually triggered the partial melt of the ice sheet during that period, this may tell us something about its future.

Manipulating the protein aggregation energy landscape: how a passive chaperone protein safeguards against disease.
Prof. Mireille Claessens (University of Twente) and Dr Christian Ottmann (Eindhoven University of Technology)
Can Parkinson’s disease be prevented by improved quality control in cells?
People are living longer, which increases the risk of quality control errors occurring in their cells. Quality control errors lead to diseases such as Parkinson’s. In this project, we will explore the potential of using small molecules to engineer an important part of the cellular quality control system. We will attempt to identify a mechanism that we can use to improve this quality control system, and thus prevent people from developing Parkinson’s disease. 

The identification and functional analysis of translationally regulated mRNAs important for stem cell identity
Dr William J. Faller (Netherlands Cancer Institute)
Stem cells are vital for our health. In the intestine, stem cells maintain this organ and heal any damage to its tissues. Changes to these cells in the intestine are known to cause diseases, such as cancer and ulcerative colitis. In this proposal, we plan to study these cells to understand how they make the proteins they need, and how this process can be hijacked by disease. This should potentially enable us to identify ways of modifying that disease process, to improve the health of this organ.

Unravelling the cellular and organism-wide consequences of polyploidy
Dr Matilde Galli (Hubrecht Institute)
Polyploid cells contain a multitude of chromosome pairs. These cells are common in various animal tissues, such as the human liver, placenta and blood, where they are thought to play an important part in generating nutrients for their environment. However, the way in which polyploid cells perform this function is poorly understood, we also have much to learn about how having more DNA leads to increased protein production and growth. In this project, we will use C. elegans (a small roundworm) as a model system, to unravel the cellular and tissue-wide effects of polyploidization.

Endothelial junctions –forces guiding vasculation
Dr Stephan Huveneers (Amsterdam University Medical Center)
The formation of new blood vessels is vital for embryonic development, but it is also involved in cancer. When laying down new blood vessels, cells move as a coordinated whole. This collective motion is made possible by means of tight contacts between individual cells. This migration of blood vessel cells is triggered by ‘leader cells’ that guide ‘follower cells’ by means of direct contacts. It was recently discovered that excessive mechanical stresses between ‘leader’ and ‘follower’ cells cause dedicated signal molecules to be recruited to these cell-to-cell contacts. We plan to identify the molecular systems involved in regulating the bonds between interacting blood vessel cells. We will then use advanced microscopy techniques to visualize the function of these molecules.

Bioinspired and Environmentally Benign Halogenations
Dr Johannes Klein (University of Groningen)
In this study, we will develop new methods for the preparation of halogenated drugs and agrochemicals that are of great importance to society. The new approach was inspired by enzymes, microscopic bio-machines that mediate similar reactions in nature.

Translation-Driven Development of Deep Learning for Simultaneous Tomographic Image Reconstruction and Segmentation
Dr Felix Lucka (Centrum Wiskunde & Informatica & University College London)
Artificial intelligence (AI) may well be the most disruptive technology developed to date. Right now, however, one of the most important challenges that we face is to realize its full potential in real-world applications in science, health care, and industry. In this project, researchers will attempt to use AI to improve image-based decision-making, an important and complex task with many applications. This will involve reconstructing and analysing images simultaneously, instead of sequentially. Besides developing novel AI approaches and computational algorithms, the team plans to identify the most common problems encountered when using AI for such tasks, and to find ways of overcoming them.

Sleep research goes wild – new insights into sleep homeostasis from studies in geese
Dr Peter Meerlo (University of Groningen)
We still know very little about sleep, particularly about how and when animals sleep in the wild, where time for rest and recovery is often limited. Take Barnacle geese, for example. In the breeding season, they are fully occupied with caring for their young. During their annual migration between Russia and the Netherlands, they fly for days on end. Can they do entirely without sleep? Or do they use the same strategy as dolphins, in which one half of the brain stays awake while the other half sleeps? Using modern, miniaturized technology, we will measure their brain activity, to find out how they sleep under natural conditions.

Habitat matching or local adaptation – how does habitat quality drive variation in cognitive traits?
Prof. Kees van Oers (NIOO-KNAW)
The influence of habitat quality on variation in cognitive traits.
Individuals consistently differ in the way they gather and process information, and how they translate this into behaviour. Could these cognitive traits be driven by variations in environmental quality? The aim of this project is to determine whether habitat quality affects cognitive processes in birds, such as the way in which they learn and solve problems, and to assess its impact on survival and reproduction. This study’s results will be a key contribution to our understanding of how cognitive processes evolve in the wild. This is all the more important today, when human activity is contributing to ongoing changes in our environment.

Fingerprinting the Higgs Sector with Effective Theories
Dr Juan Rojo (Vrije Universiteit Amsterdam) & Prof. Wouter Verkerke (Nikhef)
The Higgs boson is the most remarkable elementary particle ever discovered. It is the only particle that interreacts with anything that has mass, and is the mediator of a completely new type of fundamental force. Fingerprinting the Higgs particle to the highest possible degree of accuracy holds great promise, in terms of discovering the effects of new particles and interactions beyond the Standard Model. In this project, we will employ the powerful mathematical framework of Effective Theories to build an extensive interpretation of Higgs measurements from the Large Hadron Collider. We will efficiently develop a range of theories to extend the Standard Model and address its shortcomings.

Generating Peptactins – peptide-based activators of the immune system form a new class of immunotherapeutics
Dr Thomas Sharp (Leiden University Medical Centre)
The researchers aim to identify the signals that activate our immune system and to distil these down to their fundamental components. This will produce new and simplified ways of stimulating our immune system, giving physicians the ability to direct our body’s defences to attack cells they would ordinarily ignore, such as invading pathogens and cancer cells. It will also deliver powerful new therapies for tackling disease.

Improving treatment of metastatic cancers through game theory and dynamical systems theory
Dr K. Staňková (Maastricht University) & Dr J.L.A. Dubbeldam (Delft University of Technology)
It is incredibly difficult to successfully treat metastatic cancer. One reason for this is that cancer cells continue to evolve during treatment. In this project, we will develop new mathematical models that draw on game theory and on the theory of dynamical systems, while taking the evolutionary dynamics of cancer cells into account. Physicians can use these models to anticipate cancer cells’ responses to treatment. This research will help them to identify the ideal treatment strategy for each patient.

Temperature as a force of selection in enzyme evolution
Prof. Marcellus Ubbink (Leiden University)
Enzymes, the biomolecules that accelerate and regulate nearly all chemical reactions in living organisms, are shaped and changed by evolution. Our research will elucidate the role of temperature in the evolution of a new function for an enzyme. The results will help to make clear how evolution uses and changes the internal dynamics of each and every enzyme. An enzyme responsible for antibiotic resistance in the bacteria that cause tuberculosis will be subjected to laboratory evolution. The dynamics of the resultant mutants will then be studied, using advanced nuclear magnetic resonance techniques.

The regulation and function of a newfound immunometabolite in macrophages
Dr Jan Van den Bossche (VU University Medical Center)
How does metabolism regulate the immune system? In much the same way as you and I need energy to perform an activity, the cells of our immune system require energy to protect us against pathogens. The way in which our immune cells metabolize their resources not only provides them with energy, it also regulates their functions. We are attempting to understand exactly how this works. We have previously discovered that a specific metabolite accumulates in activated macrophages (specialized immune cells that engulf and destroy pathogens). We aim to understand how this new ‘immunometabolite’ is induced and how it functions.

Tuning immune-cell biology using macrocyclic glycopeptides
Dr Sandra van Vliet (VU University Medical Center) & Dr Seino Jongkees (Utrecht University)
Normal human cells, tumour cells, and all sorts of pathogens are covered with a unique sugar layer. This layer contains a great deal of biological information. That signature can be read by sugar-binding receptors on immune cells and translated into an appropriate immune response. In this study, we want to develop novel molecules that will enable us to manipulate these receptors, which can be used in future immune-stimulating or immune-blocking therapies.

Taming tensors – an optimization approach to computational invariant theory
Dr Michael Walter (University of Amsterdam)
Intuition tells us that it should be easier to scramble a solved Rubik’s cube than to solve a scrambled one. Computer scientists recently discovered tantalizing evidence that, for a broad and important class of puzzles with continuous symmetries, that intuition may well be mistaken! In this project, we will develop novel algorithms for solving such puzzles much more efficiently than was previously thought possible. This has important applications for ‘tensors’ (large arrays of high-dimensional data that are ubiquitous in machine learning and quantum computing, but which are notoriously difficult to work with), and promises to shed new light on fundamental questions about the speed limits of computation.

About the NWO Open Competition Domain Science-KLEIN

KLEIN grants are intended for realizing curiosity-driven, fundamental research of high quality and/or scientific urgency. The KLEIN grant enables researchers to formulate and test creative, more speculative ideas and to realize scientific innovations that can serve as a basis for the research themes of the future. There are three categories of KLEIN grants: KLEIN-1 (one scientific position), KLEIN-2 (two cooperating scientific positions) 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 the NWO Open Competition Domain Science-KLEIN at any time. A new call for proposals is expected after 1 August 2020. The Executive Board of the NWO Domain Science will decide on this in July and determine the terms and conditions of the round. Further information will follow in July 2020.

Contact

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

 

Source: NWO

Details

Science area

Exact and Natural Sciences

Programme

Open Competition Domain Science (ENW)

Objective

Curiosity driven research and talent (2015-2018)