ERC FUNDED PROJECTS

The role of intestinal bacteria in human health and disease has been intensively studied; however the viral composition of the microbiome, the virome, remains largely unknown. As many of the viruses are bacteriophages, they are expected to be a major factor shaping the human microbiome. The dynamics of the virome during early life, its interaction with host and environmental factors, is likely to have profound effects on human physiology. Therefore it is extremely timely to study the virome in depth and on a wide scale. This ERC project aims at understanding how the gut virome develops during the first year of life and how that relates to the composition of the bacterial microbiome. In particular, we will determine which intrinsic and environmental factors, including genetics and the mother’s microbiome and diet, interact with the virome in shaping the early gut microbiome ecosystem. In a longitudinal study of 1,000 newborns followed at 7 time points from birth till age 12 months, I will investigate: (1) the composition and evolution of the virome and bacterial microbiome in the first year of life; (2) the role of factors coming from the mother and from the host genome on virome and bacterial microbiome development and their co-evolution; and (3) the role of environmental factors, like infectious diseases, vaccinations and diet habits, on establishing the virome and overall microbiome composition during the first year of life. This project will provide crucial knowledge about composition and maturation of the virome during the first year of life, and its symbiotic relation with the bacterial microbiome. This longitudinal dataset will be instrumental for identification of microbiome markers of diseases and for the follow up analysis of the long-term effect of microbiota maturation later in life. Knowledge of the role of viruses in shaping the microbiota may promote future directions for manipulating the human gut microbiota in health and disease.

1 499 881 €

Start date: 2017-04-01, End date: 2022-03-31

Subjective data play an increasing role in modern economics. For instance, new welfare measurements are based on people’s subjective assessments of their happiness or their life satisfaction. A problem of such measurements is that people have no incentives to tell the truth. To solve this problem and make those measurements incentive compatible, I will introduce a new market institution, called Bayesian markets. Imagine we ask people whether they are happy with their life. On Bayesian markets, they will trade an asset whose value is the proportion of people answering Yes. Only those answering Yes will have the right to buy the asset and those answering No the right to sell it. Bayesian updating implies that “Yes” agents predict a higher value of the asset than “No” agents do and, consequently, “Yes” agents want to buy it while “No” agents want to sell it. I will show that truth-telling is then the optimal strategy. Bayesian markets reward truth-telling the same way as prediction markets (betting markets) reward people for reporting their true subjective probabilities about observable events. Yet, unlike prediction markets, they do not require events to be objectively observable. Bayesian markets apply to any type of unverifiable truths, from one’s own happiness to beliefs about events that will never be observed. The present research program will first establish the theoretical foundations of Bayesian markets. It will then develop the proper methodology to implement them. Finally, it will disseminate the use of Bayesian markets via applications. The first application will demonstrate how degrees of expertise can be measured and will apply it to risks related to climate change and nuclear power plants. It will contribute to the political debate by shedding new light on what true experts think about these risks. The second application will provide the first incentivized measures of life satisfaction and happiness.

1 500 000 €

Start date: 2016-01-01, End date: 2020-12-31

Introduction: The ability of a cancer cell to invade into the surrounding tissue is the main feature of malignant cancer progression. Diffuse Intrinsic Pontine Glioma (DIPG) is a paediatric high-grade brain tumour with no chance of survival due to its highly invasive nature. Goal: By combining state-of-the-art imaging and transcriptomics, we aim to identify and target the key mechanisms driving the highly invasive growth of DIPG. Technology advances: Two unique single cell resolution imaging techniques that we have recently developed will be implemented: Large-scale Single-cell Resolution 3D imaging (LSR-3D) that allows visualization of complete tumour specimens and intravital microscopy using a cranial imaging window that allows imaging of tumour cell behaviour in living mice. In addition, we will apply a technique of live imaging Patch-seq to perform behaviour studies together with single cell RNA profiling. Expected results: Using a glioma murine model in which the disease is induced in neonates and a new embryonic model based on in utero electroporation, we expect to gain knowledge on the progression of DIPG in maturing brain. LSR-3D imaging on human and murine specimens will provide insight into the cellular tumour composition and its integration in the neuroglial network. With intravital imaging, we will characterize invasive cancer cell behaviour and functional connections with healthy brain cells. In combination with Patch-seq, we will identify transcriptional program(s) specific to invasive behaviour. Altogether, we expect to identify novel key players in cancer invasion and assess their potential to prevent DIPG progression.  Future perspective: With the studies proposed, we will gain fundamental insights into the cancer cell invasion mechanisms that govern DIPG which may provide new potential therapeutic target(s) for this dismal disease. Overall, the knowledge and advanced technologies obtained here will be of great value for the tumour biology field.

1 500 000 €

Start date: 2019-01-01, End date: 2023-12-31

Annually 1.2 million new cases of colorectal cancer (CRC) are seen worldwide and over 50% of patients die of the disease making it a leading cause of cancer-related mortality. A crucial contributing factor to these disappointing figures is that CRC is a heterogeneous disease and tumours differ extensively in the clinical presentation and response to therapy. Recent unsupervised classification studies highlight that only a proportion of this heterogeneity can be explained by the variation in commonly found (epi-)genetic aberrations. Hence the origins of CRC heterogeneity remain poorly understood. The central hypothesis of this research project is that the cell of origin contributes to the phenotype and functional properties of the pre-malignant clone and the resulting malignancy. To study this concept I will generate cell of origin- and mutation-specific molecular profiles of oncogenic clones and relate those to human CRC samples. Furthermore, I will quantitatively investigate how mutations and the cell of origin act in concert to determine the functional characteristics of the pre-malignant clone that ultimately develops into an invasive intestinal tumour. These studies are paralleled by the investigation of stem cell dynamics within established human CRCs by means of a novel marker independent lineage tracing strategy in combination with mathematical analysis techniques. This will provide critical and quantitative information on the relevance of the cancer stem cell concept in CRC and on the degree of inter-tumour variation with respect to the frequency and functional features of stem-like cells within individual CRCs and molecular subtypes of the disease. I am convinced that a better and quantitative understanding of the dynamical properties of stem cells during tumour development and within established CRCs will be pivotal for an improved classification, prevention and treatment of CRC.

1 499 875 €

Start date: 2015-04-01, End date: 2021-03-31