Transcription of protein-coding genes is carried out by RNA polymerase II enzymes (RNAPII), which travel along the DNA to synthesize complementary RNA transcripts. When RNAPII encounters DNA damage in the template strand, this blocks its forward translocation and causes a genome-wide transcriptional arrest. To survive, cells must overcome this arrest by local DNA repair and effective restart of global gene transcription. Once stalled, RNAPII molecules themselves become major obstacles for DNA replication in dividing cells. Collisions between the transcription and replication machineries are emerging as a key source of genome instability. Our understanding of the different molecular mechanisms that repair transcription-blocking DNA lesions, or protect human cells against transcription–replications conflicts, is still far from complete. Transcription-coupled repair (TCR) is a specialized DNA repair pathway that selectively removes DNA lesions encountered while genes are actively transcribed. Through genome-wide CRISPR screens, we recently identified a network of novel TCR genes, centred around the previously uncharacterized ELOF1 gene. Drug-genetic network mapping revealed a defined set of genes that co-operates with ELOF1 in a common molecular pathway with a converging function at the intersection of TCR and DNA replication. In this project, we will combine our complementary expertise in TCR and transcription genomics (LUMC) with that in DNA replication stress pathways and genome-wide CRISPR screening (Amsterdam UMC) to dissect how the ELOF1 network orchestrates DNA repair during transcription and resolves transcription–replication conflicts in human cells. Our three objectives are: (1) to elucidate the mechanism by which ELOF1 directs TCR, (2) to dissect the roles of the ELOF1 network members in TCR, and (3) to define the role of the ELOF1 network in resolving conflicts between transcription and replication machineries. Dissecting these molecular mechanisms will reveal how the ELOF1 network safeguards genomic stability at the crossroads of transcription, repair and replication in human cells, which will provide an advanced, mechanistic understanding of the transcription-coupled DNA damage response.

This project examines how the current changes in the political information environments in European democracies affect the conditions for a healthy democracy. As a theoretical background we employ the concept of ‘political information environment’ (PIE) that includes both the supply and demand of political news and information. Supply refers to the quantity and quality of news and public affairs content provided through traditional and new media sources, demand captures the amount and type of news and information the public wants or consumes. Recent changes in the political information environment may lead to a growing number of uniformed, misinformed and selectively informed citizens, potentially endangering the functioning of democracy. To examine these concerns, the study aims at investigating the following: (1) how do citizens today gain political information and how does this relate to their political attitudes and behaviour; (2) what is the content and quality of the information citizens are exposed to; (3) where do divides between being informed and not being informed exist, across and within European societies, and (4) how can citizens be empowered to navigate and find valuable information. We will do this through a series of comparative, innovatively designed studies, including web tracking, comparative surveys, focus groups and survey-embedded experiments in 14 European countries and the US. These countries vary on a number of key contextual factors relevant for the study, covering both “young” and established democracies with different democratic traditions, media systems, and news consumption habits.

Neuromorphic computing paradigms have the potential to drastically reduce the energy cost of computing systems. This interdisciplinary project investigates new algorithms and new materials for potentially disruptive application of neuromorphic hardware. By harnessing instead of mitigating intrinsic stochastic effects, large scale computer simulations become feasible that are practically impossible today.

Todays particle physicists know that the Standard Model (SM) is not the complete theory of nature. The existence of dark matter in the universe is striking evidence that new physics must exist. The Large Hadron Collider (LHC) experiments are searching for new particles, predicted by physics models beyond the SM (BSM), in proton collision events. The BSM particles cannot be seen directly but leave their imprint in events containing a specific number of jets (collimated bunches of hadrons). To distinguish these BSM events from the overwhelming SM background, experimental analyses select events with exactly that number of jets and demand the absence of (veto) additional jet activity. Already an important tool in BSM analyses, the importance of jet vetoes will further increase when a new particle is discovered, facilitating clean and precise measurements. Jet vetoes can significantly alter the rate at which BSM particles are produced. Studies have been performed to calculate Higgs production including the jet veto effect, providing precise predictions with reliable uncertainties, which are needed to determine the Higgs couplings. However for BSM processes the jet veto effect is unexplored, even though it is expected to be more significant due to the high mass of BSM particles. My main goal is to investigate the theoretical and phenomenological consequences of jet vetoes in BSM searches. I will calculate precise and realistic predictions for BSM processes including jet vetoes and properly estimate the corresponding theory uncertainties. If no BSM particles are seen at the LHC, my results are needed to set accurate exclusion limits and can further be used to refine the search strategy. If a new particle is discovered, my results will be essential to precisely determine its properties, necessary to reveal the underlying model realised in nature.