ERC FUNDED PROJECTS

During the 20th century computer technology evolved from bulky, slow, special purpose mechanical engines to the now ubiquitous silicon chips and software that are one of the pinnacles of human ingenuity. The goal of the field of molecular programming is to take the next leap and build a new generation of matter-based computers using DNA, RNA and proteins. This will be accomplished by computer scientists, physicists and chemists designing molecules to execute ``wet'' nanoscale programs in test tubes. The workflow includes proposing theoretical models, mathematically proving their computational properties, physical modelling and implementation in the wet-lab. The past decade has seen remarkable progress at building static 2D and 3D DNA nanostructures. However, unlike biological macromolecules and complexes that are built via specified self-assembly pathways, that execute robotic-like movements, and that undergo evolution, the activity of human-engineered nanostructures is severely limited. We will need sophisticated algorithmic ideas to build structures that rival active living systems. Active-DNA, aims to address this challenge by achieving a number of objectives on computation, DNA-based self-assembly and molecular robotics. Active-DNA research work will range from defining models and proving theorems that characterise the computational and expressive capabilities of such active programmable materials to experimental work implementing active DNA nanostructures in the wet-lab.

2 349 603 €

Start date: 2018-11-01, End date: 2023-10-31

CIPHER will launch the global research initiative, Hip Hop Interpellation, pilot a new semantic digital/ethnographic web methodology, and codify the emergent discipline of global hip hop studies. It addresses the central question: why has this highly localized and authenticizing African American music translated so easily to far-flung communities and contexts around the globe? Through this specific question the project attempts to understand the foundational and broadly transferable question: how are globalization and localization related? To answer these questions CIPHER posits the Hip Hop Interpellation thesis, that hip hop spreads not as a copy of an African American original, but, through its performance of knowledge, emerges as an always already constituent part of local knowledge and practice. The theorization thus moves beyond the “hailing practices” described by Althusser’s theory of interpellation—the discursive webs that coerce ideological incorporation—to describing an interpolation that locates other histories within and through hip hop’s performed knowledges. CIPHER’s semantic web methodology tests this thesis, tracking how hip hop memes—slogans, anthems, and icons—are simultaneously produced by people and produce people. This research clears the conceptual impasse of structural “cultural imperialism” vs. agentic “cultural appropriation” debates and instrumentalizes the methodological distance between ethnographic specificity and big data generality. It does so by creating a feedback loop between digital humanities methods (crowd sourcing, semantic tagging, computational stylometry) and ethnographic fieldwork techniques (interviews, musical analysis, participant observation). The result will be an iterative map of Hip Hop Interpellation/Interpolation created by stakeholders that is transformational of our understanding of culture and/as cultural production and transferable to pressing questions about globalization and l’exception culturelle.

1 990 526 €

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

Deep brain stimulation (DBS) is an effective therapy for treating the symptoms of Parkinson’s disease (PD). Despite its success, the mechanisms of DBS are not understood and there is a need to improve DBS to improve long-term stimulation in a wider patient population, limit side-effects, and extend battery life. Currently DBS operates in ‘open-loop’, with stimulus parameters empirically set. Closed-loop DBS, which adjusts parameters based on the state of the system, has the potential to overcome current limitations to increase therapeutic efficacy while reducing side-effects, costs and energy. Several key questions need to be addressed before closed loop DBS can be implemented clinically. This research will develop a new multiscale model of the neuromuscular system for closed-loop DBS. The model will simulate neural sensing and stimulation on a scale not previously considered, encompassing the electric field around the electrode, the effect on individual neurons and neural networks, and generation of muscle force. This will involve integration across multiple temporal and spatial scales, in a complex system with incomplete knowledge of system variables. Experiments will be conducted to validate the model, and identify new biomarkers of neural activity that can used with signals from the brain to enable continuous symptom monitoring. The model will be used to design a new control strategy for closed-loop DBS that can accommodate the nonlinear nature of the system, and short- and long-term changes in system behavior. Though challenging, this research will provide new insights into the changes that take place in PD and the mechanisms by which DBS exerts its therapeutic influence. This knowledge will be used to design a new strategy for closed-loop DBS, ready for testing in patients, with the potential to significantly improve patient outcomes in PD and fundamentally change the way in which implanted devices utilise electrical stimulation to modulate neural activity.

1 999 474 €

Start date: 2015-08-01, End date: 2021-07-31

Lower back pain is a global epidemiological and socioeconomic problem. Biomaterial and cell-based therapies have been pursued for the treatment of degenerated intervertebral disc (IVD), with a number of clinical trials underway. However, the degenerated intervertebral disc has a distinct environment (e.g. altered oxygen, glucose, acidity, inflammatory cytokine levels) that is unique to an individual (i.e. patient-specific) and will ultimately determine the likelihood and rate at which regeneration can occur. A “one size fits all” approach will lead to the failure to demonstrate efficacy of advanced therapies, as they are not being designed or personalised for individual patients. This proposal envisions a future whereby advanced gene activated cell therapies are personalised (targeting regeneration or modulating inflammation) to treat back pain based on knowing the individuals unique disc microenvironment. This will be achieved through profiling of individual patient disc microenvironmental factors, with in vitro screening and in silico modelling to design cell therapies and predict regeneration outcomes (Aim 1) combined with the development of tailored functionalised gene activated biomaterials (Aim 2), to enhance matrix formation and modulate the inflammatory processes (Aim 3). Gene-based therapy offers several advantages over direct delivery of proteins or small molecules, among them the possibility of sustained efficacy and endogenous synthesis of growth factors or suppression of inflammatory factors and pathways. The platform technology (personalised gene activated biomaterials to regulate regeneration and inflammation) and knowledge (tailoring cell therapies to suit patient-specific microenvironments) generated through this research are beyond the current state-of-the-art and will provide a significant transformative scientific and clinical step change opening new horizons in minimally-invasive therapeutic strategies.

1 999 543 €

Start date: 2020-09-01, End date: 2025-08-31