ERC FUNDED PROJECTS

The composition and molecular features of tumours vary during the course of the disease, and the selection pressure imposed by the environment is a central component in this process. Evolutionary principles have been exploited to explain the genomic aberrations in cancer. However, the phenotypic changes underlying disease progression remain poorly understood. In the past years, I have contributed to identify and characterise the therapeutic implications underlying metabolic alterations that are intrinsic to primary tumours or metastasis. In CancerADAPT I postulate that cancer cells rely on adaptive transcriptional & metabolic mechanisms [converging on a Metabolic Phenotype] in order to rapidly succeed in their establishment in new microenvironments along disease progression. I aim to predict the molecular cues that govern the adaptive properties in prostate cancer (PCa), one of the most commonly diagnosed cancers in men and an important source of cancer-related deaths. I will exploit single cell RNASeq, spatial transcriptomics and multiregional OMICs in order to identify the transcriptional and metabolic diversity within tumours and along disease progression. I will complement experimental strategies with computational analyses that identify and classify the predicted adaptation strategies of PCa cells in response to variations in the tumour microenvironment. Metabolic phenotypes postulated to sustain PCa adaptability will be functionally and mechanistically deconstructed. We will identify therapeutic strategies emanating from these results through in silico methodologies and small molecule high-throughput screening, and evaluate their potential to hamper the adaptability of tumour cells in vitro and in vivo, in two specific aspects: metastasis and therapy response. CancerADAPT will generate fundamental understanding on how cancer cells adapt in our organism, in turn leading to therapeutic strategies that increase the efficacy of current treatments.

1 999 882 €

Start date: 2019-11-01, End date: 2024-10-31

"Considerable investments have been made in Europe and worldwide in research data infrastructures. Instead of a general lack of data about data, it has become apparent that the pivotal factor that drastically constrains the use of data is the absence of contextual knowledge about how data was created and how it has been used. This applies especially to many branches of SSH research where data is highly heterogeneous, both by its kind (e.g. being qualitative, quantitative, naturalistic, purposefully created) and origins (e.g. being historical/contemporary, from different contexts and geographical places). The problem is that there may be enough metadata (data about data) but there is too little paradata (data on the processes of its creation and use). In contrast to the rather straightforward problem of describing the data, the high-risk/high-gain problem no-one has managed to solve, is the lack of comprehensive understanding of what information about the creation and use of research data is needed and how to capture enough of that information to make the data reusable and to avoid the risk that currently collected vast amounts of research data become useless in the future. The wickedness of the problem lies in the practical impossibility to document and keep everything and the difficulty to determine optimal procedures for capturing just enough. With an empirical focus on archaeological and cultural heritage data, which stands out by its extreme heterogeneity and rapid accumulation due to the scale of ongoing development-led archaeological fieldwork, CAPTURE develops an in-depth understanding of how paradata is #1 created and #2 used at the moment, #3 elicits methods for capturing paradata on the basis of the findings of #1-2, #4 tests the new methods in field trials, and #5 synthesises the findings in a reference model to inform the capturing of paradata and enabling data-intensive research using heterogeneous research data stemming from diverse origins. "

1 944 162 €

Start date: 2019-05-01, End date: 2024-04-30

In dementia at the end of life, cognitive and physical decline imply that control is typically lost. CONT-END will examine control in the context of three emerging interventions which contain a controversial element of striving for control in the process of dying with dementia: advance care planning of the end of life, use of new technology to monitor symptoms when unable to self-report, and euthanasia. To perform outstanding research, the proposed research examines control at the level of clinical practice, but also at the level of end-of-life research practice. The latter provides ample opportunities for researchers to control the research process. That is, research designs are often flexible and we will study if and how this impacts research in an emotionally charged area. I will take an empirical mixed-methods approach to study the two practices in parallel. The work is organised in three related Work Packages around three research questions. (1) In a 6-country study, I will examine if and when people with dementia, family caregivers and physicians (900 respondents) find the interventions, shown on video, acceptable. (2) A cluster-randomised 3-armed controlled trial in 279 patients and their family caregivers assesses effects of two types of advance care planning differing in level of control (detailed advance treatment orders versus goal setting and coping based) on outcomes ranging from favourable to less favourable, and whether effects differ in subgroups. Cases in which the technology is preferred or applied are observed. (3) Ethnographic fieldwork in two different end-of-life research practices and a Delphi study to synthesize CONT-END’s findings assess how researchers shape findings. This greatly improves the quality of CONT-END and provides the input to develop new methodology for improving research quality and integrity.

1 988 972 €

Start date: 2018-12-01, End date: 2023-11-30

In recent decades, social media has emerged as a central arena for the construction of values. Artifacts such as YouTube videos, Facebook posts, and tweets reflect and shape what people across the globe consider important, desirable, or reprehensible. Understanding this pervasive value ecology is key to deciphering the political, cultural, and social processes governing the twenty-first century. In this project, I will conduct the first comprehensive study of values in social media. I will explore the following over-arching questions: How are values constructed through social media? Which values are emphasized in these spheres? To what extent are social media platforms associated with the globalization of values? In addressing these fundamental issues, I will apply an entirely new approach for the conceptualization and study of values. Carried out comparatively in five languages, DigitalValues will explore the interaction between three facets of value construction: (a) explicit uses of the terms “value” and “values”; (b) the implicit construction of values in genres of user-generated content; and (c) users’ interpretation and evaluation of values through both private meaning-making and public social practices of commenting, sharing, and liking. The project is theoretically, empirically, and methodologically groundbreaking in a number of ways: (1) it will be a pioneering large-scale study employing inductive methods to explore the construction of values through everyday cultural artifacts; (2) as a foundational study of values in social media, it will yield a novel theory of value construction as an intersection between individuals, technologies, and sociocultural contexts; (3) it will generate new methods for infering values from verbal texts, combining qualitative, quantitative, and automated analyses; (4) finally, it will yield a comprehensive map of values as expressed across languages and platforms, leading to a new understanding of the globalization of values.

1 985 000 €

Start date: 2019-08-01, End date: 2024-07-31