Amyloid neurodegenerative diseases are also accompanied by neuroinflammation. One of the leading roles in this inflammatory process is played by IL-1β. Pro-IL-1β is processed by protein complexes called inflammasomes, which yield active IL-1β. NLRP3 inflammasomes are activated by Aβ aggregates (Halle et al., 2008) and prion protein fibrils (Hafner-Bratkovič et al., 2012) and NLRP3 or caspase-1 deficiency protects against disease progression in the mouse model of familial Alzheimer's disease (Heneka et al., 2013). Several cellular processes and a variety of different molecular triggers have been linked to NLRP3 inflammasome activation, but the molecular mechanism of the inflammasome assembly is unknown. Based on the structure of NLRC4 we prepared a molecular model of NLRP3, which guided the rational mutagenesis of NLRP3 in order to define the roles of NACHT and LRR domains in the response to soluble and particulate NLRP3 inflammasome activators. A number of truncated NLRP3 mutants were introduced into NLRP3-deficient macrophages and tested for their ability to respond to inflammasome instigators. The insight into the molecular mechanism of NLRP3 inflammasome activation is important for the design of specific NLRP3 inflammasome inhibitors for the development of novel therapies of chronic inflammatory diseases.
B.03 Paper at an international scientific conference
COBISS.SI-ID: 5664282The project leader coordinated the project ''Life sciences researchers: the next generation'' which was financed in part by EU Social Fund and Slovenian Ministry of Education, Science and Sport. It was a consortium project of three research institutions and 13 high schools from different Slovenian regions. We organized research camps, round tables, excursions to our labs, workshops on schools, scientific lectures and research work of high-school students in the state-of-the-art laboratories. From November 2012 until the end of the project in August 2014 there were over 4500 high school student participations (some students participated in more than one activity) in our activities. The main aim of the project is to bring up a new generation of motivated and interdisciplinary young scientists with high ethical standards.
D.01 Chairing over/coordinating (international and national) projects
COBISS.SI-ID: 275025920Pain represents a very large social and clinical problem since the current treatment provides insufficient pain relief. Plasticity of pain receptors together with sensitisation of sensory neurons, and the role of soluble mediators released from non-neuronal cells render difficult to understand the spatial and temporal scale of pain development, neuronal responses and disease progression. In pathological conditions, ATP is one of the most powerful mediators that activates P2X receptors that behave as sensitive ATP-detectors, such as neuronal P2X3 receptor subtypes and P2X4 and P2X7 receptors expressed on non-neuronal cells. Dissecting the molecular mechanisms occurring in sensory neurons and in accessory cells allows to design appropriate tissue- and cell- targeted approaches to treat chronic pain.
F.30 Professional assessment of the situation
COBISS.SI-ID: 3694075