Building Blocks of Life grants

19 December 2016

Sixteen multidisciplinary consortia have been allocated more than ten million euros to explore the building blocks of life.

With the Building Blocks of Life programme, the Netherlands Organisation for Scientific Research (NWO), the Netherlands Organisation for Health Research and Development (ZonMw), the Foundation for Fundamental Research on Matter (FOM), and the STW Technology Foundation have awarded over ten million euros to researchers in sixteen different public-private consortia. The research of the multidisciplinary teams involved will focus on obtaining a better understanding of cellular systems, from the perspective of molecular building blocks. The successful consortia operate in a domain where physics, chemistry, biology, medicine, computer science and systems analysis intersect.

The cell, and its multitude of components, forms the basis of life. The goal of the Building Blocks of Life programme is to gain a fundamental understanding of the molecular structures, dynamics and interactions at the heart of cellular functions. Ultimately, the Building Blocks of Life programme aims to apply this knowledge in areas such as the development of medicines, measuring equipment, food and crops.

The funding made available within the Building Blocks of Life programme is intended to strengthen multidisciplinary partnerships between academic researchers and private companies. The Building Blocks of Life programme will provide a more in-depth understanding of the building blocks of life, while also promoting the social and economic implementation of this new knowledge.

The Building Blocks of Life programme is a cross-sectoral initiative of the NWO divisions of Earth and Life Sciences, Chemical Sciences, FOM/Physics, ZonMw and STW. The programme was set up in collaboration with the Top Sectors of Agri&Food, Chemicals, High Tech Systems & Materials, Life Sciences & Health, and Horticulture & Propagation Materials. Various consortia of academic researchers and companies submitted interdisciplinary research plans. The added value of consortia above and beyond that of existing partnerships was one of the four assessment criteria, in addition to scientific quality, level of compatibility with the programme, and potential for social and economic implementation. The private partners contribute 10% of the project budget. In this round, NWO received a total of 48 eligible applications.

Grants awarded for Building Blocks of Life

Sugary building blocks of cells
Prof. J.M.F.G. Aerts, Leiden University - Sanofi Genzyme
Glucosylceramide (GlcCer), a component of all cells, consists of glucose (a sugar) and ceramide (a fat). The hereditary defective breakdown of GlcCer results in Gaucher’s disease. It also leads to the accumulation of various glycosylated metabolites which seldom occur normally, if at all. It has recently been demonstrated that there are causal links between abnormalities in GlcCer metabolism and various diseases such as Parkinson’s (and other forms of dementia) and Kahler’s disease. The goal of this project is to gain an understanding of the molecular relationship between GlcCer metabolism and the above diseases, with the aim of developing new diagnostics and formulating new treatment options.

Novel perspective on cholera infection
Prof A. Briegel, Leiden University – FEI Company
The emergence of antibiotic resistance underscores the need for new methods of treating the life-threatening infectious disease caused by cholera bacteria. This demands a better understanding of the interplay between the bacteria and their host at all stages of the infection process. Like humans, zebrafish are natural hosts for cholera bacteria. The minute larvae of this model organism are particularly suitable for microscopic examination. For the very first time, using a combination of the latest cryo-electron microscopy techniques and innovative chemical labelling methods, it will be possible to show – in ultrastructural detail – exactly how cholera bacteria adapt to the challenge of colonizing their host’s intestinal tract.

Interactions between gut microbes and the intestinal immune system, in a human gut-on-a-chip
Dr H. Bouwmeester, Wageningen University & Research - DSM Food Specialties, Galapagos, Metalmembranes, Micronit Microfluidics - RIKILT
How can we study interactions between chemical compounds, food ingredients, microorganisms, intestinal cells and the immune system in the human gut? An innovative gut-on-a-chip module will be developed for this purpose. This chip will feature a sufficiently high degree of biological complexity to enable researchers to effectively study the interaction between the various components in the intestine. It is important for the researchers to be able to simulate micro-environments (like the one in the human intestine) in the laboratory as accurately as possible. The integrated gut-on-a-chip system will contain all the building blocks of a functional intestine. The use of this system might also be a significant factor in the reduction of animal testing.

New tools for studying and perfecting improving yeast cell factories
Dr P.A.S. Daran-Lapujade, Delft University of Technology – DSM Food Specialties
The use of microorganisms as ‘cell factories’ for the production of chemicals from renewable resources is an important key to sustainable development. These processes require microbes with new properties. To this end, microbes’ genetic information – which consists of thousands of different genes – has to be will need thoroughly investigated to be studied in minute detail, and extensively modified. To date, these changes have been introduced step by stepstepwise,; in other words, slowly. The newly discovered CRISPR-Cas bacterial immune system enables researchers to reprogram genomes (the ‘software’ of microbial cell factories) much more rapidly and precisely than was previously possible. The goal of this project is to boost the effectiveness efficiency of CRISPR-derived tools still even further. The main purpose is to rapidlyenable the rapid construction generate – and study – of countless new variations of the metabolism of baker's yeast. In this way, thise project will offer unique and novel opportunities for fundamental research and for the industrial use of yeast and other microbes.

Bricks and mortar – how archaea build their cell membranes
Prof. A.J.M. Driessen, University of Groningen – DSM Ahead Innovative Synthesis and Kinetic Evaluation Instruments B.V.
Archaea are microorganisms some of which live under extreme conditions, at temperatures of up to 120°C and in highly acidic environments. Their cell membrane, which is composed of complex lipids, is particularly impermeable. Exactly how archaea make these membrane lipids is still something of a mystery. This study aims to solve this puzzle by feeding archaea synthetic precursors of these lipids (labelled with the stable carbon isotope ¹³C) and then analysing the products. The enzymes involved will also be identified. The knowledge gained in this way will be used to combat the tuberculosis bacterium, which also uses complex lipids in its membrane to protect itself from our immune system.

Cut out for the future!
Prof. J.H. Gribnau, Erasmus MC - DDL
Gene expression is effectively controlled by chemically changing the DNA at specific sites, by means of DNA methylation. An entirely novel assay will be developed, as a cheap and efficient way of reading out these changes. This is done with the aid of an enzyme that specifically cuts sections of DNA with methyl groups out of the genome. Sequencing is then used to determine the exact position of these methylated sections of DNA. The importance of a technique for reading out these changes is that it will help us to understand the role of DNA methylation in gene regulation in general. More specifically, it will improve our understanding of – and ability to predict – disease progression in bowel cancer and cervical cancer.

Building blocks, biomarkers and intervention options for muscle aging
Prof. J.H.J. Hoeijmakers, Erasmus MC - Nestlé Institute of Health Sciences
Remaining vital in old age is not only important to individuals, it is also important to society at large. One of the main factors that cause elderly people to lose their independence is decreased muscle function. In this project, the consortium partners plan to investigate which of the building blocks of muscle are responsible for the decline in function with ageing, how this could be detected already at a young age, and how it might be prevented by dietary interventions.

How can DNA damage be lethal to tumours?
Prof. R. Kanaar, Erasmus MC –Philips Electronics Nederland B.V.
Research on cells grown in culture flasks has taught us a great deal about how molecules detect and repair DNA damage. One of the methods used involves filming living cells and tracking the DNA-repair proteins, which are labelled with miniscule lights. The knowledge obtained in this way enables physicians to select individual cancer patients for customized therapy. Normally, however, tumour cells exist within a three-dimensional structure that is much more complex than the flat bottom of a culture flask. For this reason, researchers are culturing thin slices of living tumours on so-called ‘chips’, which are better able to simulate the tumour’s environment in the body. DNA damage response proteins in tumours will be labelled with miniscule lights to find out how they work in cells that are still part of a tumour. The knowledge obtained in this way will make it possible to precisely select the appropriate therapy for each individual patient, before their treatment commences.

A three-dimensional standard atlas for tumours
Prof J. Klumperman, UMCU- Genentech, Delmic
Cancer cells can be killed by our immune system’s T cells, but some tumour cells are able to avoid this fate, literally by keeping the T cells at a distance. We do not know exactly how they do this, or which molecules are involved. The researchers will use a novel microscopy technique to create a three-dimensional atlas of a cancer cell and its immediate surroundings. This will show exactly how, and in what regions, the T cells are held at bay, and which molecules are responsible for this. If these molecules can then be deactivated, the tumours can be sensitized to infiltration by T cells and to cancer immunotherapy.

Tailored microalgae for sustainable oil production
Dr P.P. Lamers, Wageningen University & Research - Biostream
In today’s society, there is a growing demand for sustainably produced, high-quality oils for use in food, fuels and chemical applications. Microalgae are unicellular micro plants that can produce such oils, by using photosynthesis to convert light energy into energy reserves. Microalgae can grow in salt water and in areas that are not suitable for agriculture, which makes them a good alternative to less sustainable (plant-based) sources of oil. This research focuses on further improving microalgae in terms of increased oil production and enhanced oil quality. Another of its goals is to identify the genetic factors that underpin these properties.

Stress and Hormones Induce Test Tube Babies in Plants
Dr R. Offringa, Leiden University - KWS Saat, ENZA Zaden, Vilmorin & Cie, Iribov - Vegenov
The plant kingdom is characterized by a high level of developmental plasticity, including the ability of in vitro cultured plant cells to form embryos from cells other than the fertilized egg. In vitro embryogenesis is induced in tissue culture by applying stress or plant hormones, but very little is known about how these two different treatments reprogram cells to form embryos. We will use different in vitro embryogenesis model systems, as well as a combination of chemical biology and molecular genetic approaches to understand where and how stress and hormone signaling pathways converge to promote in vitro embryogenesis.

Light in the darkness: the influence of light quality on the development of plant roots
Prof. R. Pierik, Utrecht University - Limagrain Nederland B.V. and Rijk Zwaan Breeding B.V.
Changes in the light spectrum enable plants to sense when they are in danger of being overshadowed by the surrounding vegetation. They respond to this threat by rapidly growing upwards towards the light, while the growth of their roots actually decreases. Both of these changes reduce investments in the edible parts of plants. In this project, we will attempt to identify the nature of the signals sent from the shoot to the root, and to localize and identify those processes within plant roots that are affected by such signals. However, different root growth processes also influence one another. Accordingly, the researchers will combine experiments with mathematical models, to sort the wheat from the chaff and find out exactly what is going on.

E pluribus unum: from single cells to mini-organs
Prof. S.J. Tans, FOM Institute AMOLF - Hubrecht Organoid Technology
Cells must cooperate in order to form and maintain organs. This issue is adressed using ‘organoids’, which are mini organs that can grow outside the body, in combination with advanced microscopy and quantitative biophysical analysis techniques. The goal is to understand how local interactions between cells lead to order and regulation at the level of entire organs. By comparing healthy and diseased organoids, researchers will identify changes in the behaviour of a few individual cells that lead to symptoms of disease at the level of the entire organ.

Getting to grips with yeast metabolism under dynamic conditions
Prof. B. Teusink, Vrije Universiteit Amsterdam - DSM Food Specialities B.V.
The metabolism of Baker’s yeast is not only essential for bread and beer, it is also of pivotal importance to industrial fermentations that produce biofuels and chemical building blocks from renewable resources. We know what reactions are involved (the roadmap), but we do not yet understand how the activities of these reactions (the traffic) are normally regulated, nor how they might be influenced (e.g. road widening or traffic lights), especially not under dynamic conditions such as those found in nature and in large fermenters. In order to better understand this regulation, the researchers will create a computer model capable of simulating the chemical flows involved. This is a fundamental scientific challenge with major practical applications.

How the pores in our cell nuclei play a role in in neurodegenerative diseases such as ALS
Dr L.M. Veenhoff, University Medical Center Groningen - Pivot Park Screening Centre
It was recently discovered that several neurodegenerative diseases, such as ALS, are associated with problems involving transport to and from cell nuclei. That transport process is mediated by the nuclear pore complex. The researchers will be studying certain organic substances produced in ALS patients to find out exactly how they are associated with changes in nuclear transport. The researchers plan to tackle this problem in four different ways. Firstly through the use of artificial mimics of pore complexes, secondly by means of real nuclear pore complexes in living yeast cells, thirdly using computer models, and finally by identifying chemicals that influence this process, which could provide insights into potential drugs. The knowledge gained by the researchers, as well as the substances they discover, may eventually be used to help combat these diseases.

How are the genome’s dynamics and plasticity involved in health or disease?
Dr K.S. Wendt, Erasmus MC - Harbour Antibodies
The genome’s 3D structure and internal interactions are determinants of gene activity and the intervening non‐coding parts of the chromosomal DNA, for example enhancers, play an important role to shape these structures. Despite the tremendous progress that has recently been made, the 3D dynamics of the genome (which can vary from cell to cell) is still quite obscure, as our understanding is primarily based on static observations on large cell pools. Accordingly, a multidisciplinary team and a biotechnology company have set themselves a number of ambitious targets in this regard. These involve working out the structure and dynamics of the genome in normal and abnormal (diseased) cells, through the development of integrated biochemical methods and advanced microscopy techniques.

Source: NWO