Tuberculosis (TB) is a global disease. With over 1.6 million deaths in 2017 alone and an estimated one quarter of the world’s population infected with Mycobacterium tuberculosis (Mtb), the etiological agent, TB is found throughout the world. Mtb is highly successful as a pathogen, in part due to its distinct and hydrophobic outer membrane (OM) and its type VII secretion systems (T7SSs). Although critical for the success of Mtb as a pathogen, the structure and mechanism of T7SSs are still poorly understood. In Mtb, five T7SSs (ESX-1 to 5) perform diverse functions such as immunomodulation, virulence, uptake of nutrients and iron. In T7SSs, four conserved membrane components, EccB/C/D/E assemble into a hexameric inner membrane complex, with a fifth transiently interacting membrane component, MycP. We have previously shown a low resolution, hexameric structure of the EccB/C/D/E membrane complex and recently two models of a dimeric subcomplex have been published. However, little is known on the structure of the entire core complex (including MycP), what is the secretion pore and how is it gated, or how secretion takes place through the OM, making this research proposal timely and necessary. The aim of this fellowship is to elucidate the underlying mechanism of secretion through the diderm cell envelope by: 1 - Elucidating the high-resolution structure of the hexameric T7SS membrane complex of Mtb. 2 - Investigate the molecular and structural mechanisms behind the OM translocation process. The results stemming from this proposal have the potential to aid and steer structure-based drug designs against Mtb. The host lab has pioneered cryo-EM of secretion systems and has state-of-the-art infrastructure and know-how that will provide the fellow with the best possible training and chances of success. With appropriate measures put in place, this project will drive forward mycobacterial research and will serve as a starting platform for identifying new possible drug targets.

ProgrammE in Costing, resource use measurement and outcome valuation for Use in multi-sectoral National and International health economic evaluAtions (PECUNIA) addresses the call SC1-PM-20-2017 Methods research for improved health economic evaluation. The consortium brings together 10 partners from 6 countries with complementary methodological expertise. It represents differing health care systems with varying feasibility and acceptability of economic evaluations in evidence-informed decision making. Some countries have established national unit cost programmes (DE, NL, UK), some early stage initiatives (AT, ES, HU). Availability of health utility value sets for outcome evaluations and requirements in terms of the primary analytical perspective of economic evaluations (health & social care vs. societal) also differ. Over 36 months, PECUNIA will develop standardised, harmonised and validated multi-sectoral, multi-national and multi-person methods, tools and information for 1) self-reported resource use measurement, 2) reference unit cost valuation, 3) cross-national health utility assessment, and 4) broader wellbeing measurement. To achieve the widest impact possible and exploit its disruptive innovation potential for end users, decision makers, payers and the industry, the work will be executed in close collaboration with 5) external scientific advisors and broad outreach to all relevant stakeholders. Considering feasibility and relevant societal challenges in the European health systems, selected mental health disease areas (depression, schizophrenia, PTSD) will be used as illustrative examples for cost assessment. PECUNIA will lead to better understanding of the variations in costs and outcomes within and across countries, improve the quality, comparability and transferability of economic evaluations in Europe, and support the feasibility of broader economic and societal impacts measurement and valuation in multi-sectoral economic evaluations also for HTA.

As robots become more omnipresent in our society, we are facing the challenge of making them more socially competent. However, in order to safely and meaningfully cooperate with humans, robots must be able to interact in ways that humans find intuitive and understandable. Addressing this challenge, we propose a novel approach for understanding and modelling social behaviour and implementing social coupling in robots. Our approach presents a radical departure from the classical view of social cognition as mind-reading, mentalising or maintaining internal rep-resentations of other agents. This project is based on the view that even complex modes of social interaction are grounded in basic sensorimotor interaction patterns. SensoriMotor Contingencies (SMCs) are known to be highly relevant in cognition. Our key hypothesis is that learning and mastery of action-effect contingencies are also critical to enable effective coupling of agents in social contexts. We use “socSMCs” as a shorthand for such socially rele-vant action-effect contingencies. We will investigate socSMCs in human-human and human-robot social interaction scenarios. The main objectives of the project are to elaborate and investigate the concept of socSMCs in terms of information-theoretic and neurocomputational models, to deploy them in the control of humanoid robots (PR2, REEM-C) for social entrainment with humans, to elucidate the mechanisms for sustaining and exercising socSMCs in the human brain, to study their breakdown in patients with autism spectrum disorders, and to benchmark the socSMCs approach in several demonstrator scenarios. Our long term vision is to realize a new socially competent robot technology grounded in novel insights into mechanisms of functional and dysfunctional social behavior, and to test novel aspects and strategies for human-robot interaction and cooperation that can be applied in a multitude of assistive roles relying on highly compact computational solutions.