The 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: 275025920Pregl award for excellent achievements was awarded to dr. Iva Hafner Bratkovič for her work on molecular mechanisms of neurodegenerative diseases, particularly on the mechanisms of prion protein conversion and the mechanisms of neuroinflammation in neurodegenerative diseases. Iva Hafner Bratkovič also engages into work with youth. She coordinated extremely successful project: Life sciences researchers:the next generation.
E.01 National awards
COBISS.SI-ID: 5843226Members of the project are strongly involved in popularization of science among lay public. They often present their scientific achievements in educational and science program on national TV and radio. In the case of high-impact achievements or awards they were also invited to present in prime-time news programs. Project leader also presented designer cell-based device for chronic wound healing in entrepreneur TV show ''Prava ideja''. She also presented various aspects of neurodegeneration in TV shows ''Ugriznimo znanost'' and '' Dobro jutro''.
D.10 Educational activities
COBISS.SI-ID: 5843482Amyloid 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. We were able to define the minimal fully responsive NLRP3 truncated variant, explore the oligomerization state of NLRP3 and define the domains, which are able to respond to triggers, but do not support NLRP3 inflammasome assembly. 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: 5664282NLRP3 inflammasome is a multiprotein complex which forms within cells in response to various triggers (ATP, microbial components, crystals, amyloid plaques etc.) The complex consists of a sensor protein NLRP3, adaptor protein ASC and procaspase-1, which self activates and converts cytokine pro-forms of IL1b and IL 18 into their mature forms. Despite increasing knowledge on the involvement of NLRP3 in a variety of pathologies, the mechanism of inflammasome activation is not understood and inhibitors targetting early steps of inflammasome assembly are lacking. Based on available structures of the proteins that comprise the inflammasome and on the models of NLRP3 we designed two groups of putative inhibitory peptides which were likely to inhibit the formation of the inflammasome. We showed that peptides inhibit the activation of caspase-1 and the release of IL-1β and IL-18 from myeloid cells in a concentration-dependent manner. Furthermore, we found that some of the peptides specifically inhibited the NLRP3 inflammasome and not other inflammasomes. In 2015 two students received Masters Degree including work described above. Additionally, the results were presented as a poster on FEBS3+ conference.
D.09 Tutoring for postgraduate students
COBISS.SI-ID: 6078490