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Epigenetic inheritance is the transmission of information, generally in the form of DNA methylation or post-translational modifications on histones that regulate the availability of underlying genetic information for transcription. RNA itself feeds back to contribute to histone modification. Sequence accessibility is both a matter of folding the chromatin fibre to alter access to recognition motifs, and the local concentration of factors needed for efficient transcriptional initiation, elongation, termination or mRNA stability. In heterochromatin we find a subset of regulatory factors in carefully balanced concentrations that are maintained in part by the segregation of active and inactive domains. Histone H3 K9 methylation is key to this compartmentation. C. elegans provides an ideal system in which to study chromatin-based gene repression. We have demonstrated that histone H3 K9 methylation is the essential signal for the sequestration of heterochromatin at the nuclear envelope in C. elegans. The recognition of H3K9me1/2/3 by an inner nuclear envelope-bound chromodomain protein, CEC-4, actively sequesters heterochromatin in embryos, and contributes redundantly in adult tissues. Epiherigans has the ambitious goal to determine definitively what targets H3K9 methylation, and identify its physiological roles. We will examine how this mark contributes to the epigenetic recognition of repeat vs non-repeat sequence, and mediates a stress-induced response to oxidative damage. We will examine the link between these and the spatial clustering of heterochromatic domains. Epiherigans will develop an integrated approach to identify in vivo the factors that distinguish repeats from non-repeats, self from non-self within genomes and will examine how H3K9me contributes to a persistent ROS or DNA damage stress response. It represents a crucial step towards understanding of how our genomes use heterochromatin to modulate, stabilize and transmit chromatin organization.

Methylene blue is the first fully synthetic drug used in medicine, the most effective and safe medicines needed in a health system. In addition, thioethers derivatives are important materials that are used in organic, bioorganic and medicinal chemistry and are also known to exhibit different biological activities such as antioxidant and antibacterial. These compounds are synthesized commercially by chemical methods that suffer from significant limitations, such as expensive and toxic reagents, solvents, tedious work-up, safety problems. Organic electrosynthesis is recognized as a typical environmentally friendly process with features that many of which cannot be achieved by other methods. Most electroorganic processes are performed under reagentless and mild conditions in one step using efficient and ecofriendly methods and are in agreement with all the principles of green chemistry. Within this field, the use of microreactors in continuous flow is also concurrent with electrochemistry because of its convenient advantages over batch, such as no supporting electrolyte at all, due to the small distance between electrodes; high electrode surface-to-reactor volume ratio, short residence time and etc. This project aims to fabricate an electrochemical flow microreactor by the novel method of photolithography to decrease the interelectrode gap below 100µm. Thus, the resulting device should be suited to the electrosynthesis of a wide range of reactions without a supporting electrolyte solution. Through the present project, we also aim electrochemical synthesis of methylene blue and some new thioethers derivatives for the first time with a facile one-pot and supporting electrolyte-free method. Overall, this method has shown to be a promising tool for electrosynthesis and improving the outcome of standard batch cells. As well as, during the whole of the project the ER will gain maximum knowledge in microfluidic integrated devices and benefit from entrepreneurship skills.

Background: EU countries face large health challenges to combat chronic diseases. Recently, systems medicine has emerged as a promising discipline to accelerate the translation of basic research into applications for improved diagnostics and personalized treatment. Its power arises from the integration of laboratory and computational approaches crossing research disciplines and sectors to solve clinical questions. COSMIC delivers the next generation of leading, entrepreneurial, and innovative systems medicine professionals having expertise, skills, and experience to successfully combat complex human disorders. These professional will find excellent career opportunities. COSMIC focuses on B-cell neoplasia and rheumatoid arthritis, prototypical diseases originating from abnormal functioning of immune cells, often resulting in similar antigen specificities. COSMIC enables Early Stage Researchers to play a leading role in this exciting field. Approach: COSMIC develops and integrate experimental and computational approaches and establish a unique cross-fertilization between oncology and auto-immunity. In addition to transferable skills, the training program focuses on establishing a double expertise in laboratory and computational to address clinical questions. It involves a wide-range of stakeholders: (pre)clinical departments, companies, patient groups, students, and the general public. COSMIC will establish a link with the leading European EASyM and ISBE initiatives, and aims to harmonize systems medicine training throughout Europe by connecting to other EU (Marie Curie systems medicine) training initiatives. Impact: COSMIC (i) significantly improves ESR career perspectives (ii) leads to new public-private collaborations increasing competitiveness for companies; (iii) contributes to future oncology and immunology medical care; (iv) contributes to the EU systems medicine best practices.

Antibiotic resistance is a global health issue that threatens modern medicine and how we treat bacterial infections. Investigating how bacteria live is important to fight against antibiotic resistance as it can lead to new approaches for dealing with bacterial infections, and new targets for antibiotics. The research project we are proposing aims to further our understanding of a system called Tol-Pal in a class of bacteria called Gram negatives. Tol-Pal has been shown to have a role in cell division and is important for the growth of Gram-negative bacteria. At the moment, we do not fully understand how the components of Tol-Pal work together to carry out this function. In this project we hope to use structural biology techniques to see what a complex of three of the proteins in the Tol-Pal system, TolQRA, look like. We hope that finding out what TolQRA looks like will help us to investigate the mechanism of TolQRA within the Tol-Pal system, and further our understanding of Gram-negative bacteria and how they work.

Metastasis is the primary cause of cancer deaths. For most cancers, the identification and the mechanisms by which the metastatic initiating cells (MICs) successfully establish a secondary tumour at a distant site from their primary tumour remains elusive (1). New animal models are needed to better understand the clonal dynamic and molecular mechanisms guiding different steps of the metastatic cascades in vivo, given the tremendous heterogeneity of tumours (2-7) and the limited capacity to trace multiple genetic clones in parallel with the traditional reporter mice (8). This will aid the design of new methods for early diagnosis and the monitoring of patients with metastasis, as well as the development of new strategies that target or prevent metastasis. In this project, I will use clonal lineage tracing with Poly-Lox reporter that enables tracing of over 200’000 clones (9) and confetti reporter (10) combined with single cell transcriptional profiling in order to define the cellular and molecular mechanisms that regulate the metastatic cascade in vivo in two different mouse models of squamous cell carcinoma and breast tumour. With the immunostaining, FACS and single cell sequencing analyses I will study the role of various fibroblast sub-populations in affecting the extravasion and establishment of tumour cells at the site of metastasis.

Cilia are essential hair-like structures presented at the surface of eukaryotic cells that allow motility, fluid flow and complex inter- and intracellular signalling events. Nine pairs of microtubules organized in a cylindrical shape called axoneme form the backbone of cilia. The formation and maintenance of cilia is dependent on a multi-subunit protein complex termed the intraflagellar transport (IFT) complex that actively delivers axonemal building blocks such as tubulin from the base to the tip of growing cilia. Lack of cilia or its miss-construction leads to severe developmental diseases called ciliopathies. Despite its fundamental role in cilium biogenesis, the process of tubulin recruitment, loading and unloading by the IFT machinery remains poorly understood. In this proposal, I aim to elucidate the mechanism of tubulin loading onto IFT complexes by determining high-resolution structures of intraflagellar transport (IFT) complexes bound to tubulin. Details about the IFT-tubulin interaction interface will be obtained by a combination of biochemical techniques like site directed photo- and chemical crosslinking followed by mass-spectrometry analysis and the structural biology techniques X-ray crystallography and single particle cryo-electron microscopy (cryo-EM). Ultimately, this study will enrich our understanding of cilium biogenesis and homeostasis by providing the first insight at atomic resolution into cargo selection and loading onto IFT machinery.

Designers draw extensively to externalize their ideas and communicate with others. However, drawings are currently not directly interpretable by computers. To test their ideas against physical reality, designers have to create 3D models suitable for simulation and 3D printing. However, the visceral and approximate nature of drawing clashes with the tediousness and rigidity of 3D modeling. As a result, designers only model finalized concepts, and have no feedback on feasibility during creative exploration. Our ambition is to bring the power of 3D engineering tools to the creative phase of design by automatically estimating 3D models from drawings. However, this problem is ill-posed: a point in the drawing can lie anywhere in depth. Existing solutions are limited to simple shapes, or require user input to “explain” to the computer how to interpret the drawing. Our originality is to exploit professional drawing techniques that designers developed to communicate shape most efficiently. Each technique provides geometric constraints that help viewers understand drawings, and that we shall leverage for 3D reconstruction. Our first challenge is to formalize common drawing techniques and derive how they constrain 3D shape. Our second challenge is to identify which techniques are used in a drawing. We cast this problem as the joint optimization of discrete variables indicating which constraints apply, and continuous variables representing the 3D model that best satisfies these constraints. But evaluating all constraint configurations is impractical. To solve this inverse problem, we will first develop forward algorithms that synthesize drawings from 3D models. Our idea is to use this synthetic data to train machine learning algorithms that predict the likelihood that constraints apply in a given drawing. In addition to tackling the long-standing problem of single-image 3D reconstruction, our research will significantly tighten design and engineering for rapid prototyping.

The design and realization of age-friendly living and working environments is a huge challenge that we have just only started to address as the number of older citizens who are and want to continue being active members of society and live independently is constantly increasing. SmartWork builds a worker-centric AI system for work ability sustainability, integrating unobtrusive sensing and modelling of the worker state with a suite of novel services for context and worker-aware adaptive work support. The unobtrusive and pervasive monitoring of health, behaviour, cognitive and emotional status of the worker enables the functional and cognitive decline risk assessment. The holistic approach for work ability modelling captures the attitudes and abilities of the ageing worker and enables decision support for personalized interventions for maintenance/improvement of the work ability. The evolving work requirements are translated into required abilities and capabilities, and the adaptive work environment supports the older office worker with optimized services for on-the-fly work flexibility coordination, seamless transfer of the work environment between different devices and different environments (home, office, on the move), and on-demand personalized training. The SmartWork services and modules also empower the employer with AI decision support tools for efficient task completion and work team optimization through flexible work practices. Optimization of team formation, driven by the semantic modelling of the work tasks, along with training needs prioritization at team level to identify unmet needs, allow employers to optimize tasks (e.g. needed resources), shifting focus on increased job satisfaction for increased productivity. Formal and informal carers are able to continuously monitor the overall health status and risks of the people they care for, thus providing full support to the older office worker for sustainable, active and healthy ageing.

AQSuS aims at experimentally implementing analogue quantum simulation of interacting spin models in two-dimensional geometries. The proposed experimental approach paves the way to investigate a broad range of currently inaccessible quantum phenomena, for which existing analytical and numerical methods reach their limitations. Developing precisely controlled interacting quantum systems in 2D is an important current goal well beyond the field of quantum simulation and has applications in e.g. solid state physics, computing and metrology. To access these models, I propose to develop a novel circuit quantum-electrodynamics (cQED) platform based on the 3D transmon qubit architecture. This platform utilizes the highly engineerable properties and long coherence times of these qubits. A central novel idea behind AQSuS is to exploit the spatial dependence of the naturally occurring dipolar interactions between the qubits to engineer the desired spin-spin interactions. This approach avoids the complicated wiring, typical for other cQED experiments and reduces the complexity of the experimental setup. The scheme is therefore directly scalable to larger systems. The experimental goals are: 1) Demonstrate analogue quantum simulation of an interacting spin system in 1D & 2D. 2) Establish methods to precisely initialize the state of the system, control the interactions and readout single qubit states and multi-qubit correlations. 3) Investigate unobserved quantum phenomena on 2D geometries e.g. kagome and triangular lattices. 4) Study open system dynamics with interacting spin systems. AQSuS builds on my backgrounds in both superconducting qubits and quantum simulation with trapped-ions. With theory collaborators my young research group and I have recently published an article in PRB [9] describing and analysing the proposed platform. The ERC starting grant would allow me to open a big new research direction and capitalize on the foundations established over the last two years.

The FORCOAST project addresses the topic “DT-SPACE-01-EO-2018-2020 COPERNICUS MARKET UPTAKE” which seeks to foster market development exploiting the value of Copernicus Earth Observation Products. FORCOAST aims to provide information services that offer high resolution water quality and met-ocean indicators in coastal and nearshore areas, to improve operation, planning and management of different marine activities in the sectors of wild fisheries, oystergrounds restoration, and bivalve mariculture. FORCOAST information products and services will be co-designed with stakeholders, thereby ensuring that these products and services are tailored to meet their needs. FORCOAST is developing, testing and demonstrating, in operational mode, novel Copernicus-based downstream information services that will incorporate Copernicus Marine, Land and Climate Services Products, local monitoring data and advanced modelling in the service. The services will integrate Copernicus Earth Observation Products with local models and other diverse data sources (local, regional or global) with ICT (enhancing new frontiers opened by web, and use of cloud) across the different market segments. FORCOAST will provide consistent coastal data products, based on a standardized data processing scheme. FORCOAST is supporting the concept of developing an advanced platform and cloud computing for Copernicus-based downstream services utilizing one of the DIAS systems. The availability and accessibility of data and derived products generated will stimulate their exploitation by a wide range of user communities in the targeted sectors. FORCOAST will provide those services in eight pilot service uptake sites covering five different regional waters (North Sea, Baltic Sea, Mediterranean Sea, Black Sea and the coastal Atlantic Ocean).