Pauwels L.,VIB |
Goossens A.,Ghent University
Plant Cell | Year: 2011
Jasmonates are phytohormones that regulate many aspects of plant growth, development, and defense. Within the signaling cascades that are triggered by jasmonates, the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins play a central role. The endogenous bioactive JA-Ile conjugate mediates the binding of JAZ proteins to the F-box protein CORONATINE INSENSITIVE1 (COI1), part of the Skp1/Cullin/F-box SCFCOI1 ubiquitin E3 ligase complex. Upon the subsequent destruction of the JAZ proteins by the 26S proteasome, multiple transcription factors are relieved from JAZ-mediated repression, allowing them to activate their respective downstream responses. However, many questions remain regarding the targets, specificity, function, and regulation of the different JAZ proteins. Here, we review recent studies on the model plant Arabidopsis thaliana that provided essential and novel insights. JAZ proteins have been demonstrated to interact with a broad array of transcription factors that each control specific downstream processes. Recruitment of the corepressor TOPLESS unveiled a mechanism for JAZ-mediated gene repression. Finally, the presence of JAZ proteins was also found to be regulated by alternative splicing and interactions with proteins from other hormonal signaling pathways. Overall, these contemporary findings underscore the value of protein-protein interaction studies to acquire fundamental insight into molecular signaling pathways. © 2011 American Society of Plant Biologists. All rights reserved.
Agency: Cordis | Branch: H2020 | Program: ERC-COG | Phase: ERC-CoG-2014 | Award Amount: 2.00M | Year: 2016
Neurodegeneration is characterized by misfolded proteins and dysfunctional synapses. Synapses are often located very far away from their cell bodies and they must therefore largely independently cope with the unfolded, dysfunctional proteins that form as a result of synaptic activity and stress. My hypothesis is that synaptic terminals have adopted specific mechanisms to maintain robustness over their long lives and that these may become disrupted in neurodegenerative diseases. Recent evidence indicates an intriguing relationship between several Parkinson disease genes, synaptic vesicle trafficking and autophagy, providing an excellent entry point to study key molecular mechanisms and interactions in synaptic membrane trafficking and synaptic autophagy. We will use novel genome editing methodologies enabling fast in vivo structure-function studies in fruit flies and we will use differentiated human neurons to assess the conservation of mechanisms across evolution. In a complementary approach I also propose to capitalize on innovative in vitro liposome-based proteome-wide screening methods as well as in vivo genetic screens in fruit flies to find novel membrane-associated machines that mediate synaptic autophagy with the ultimate aim to reveal how these mechanisms regulate the maintenance of synaptic health. Our work not only has the capacity to uncover novel aspects in the regulation of presynaptic autophagy and function, but it will also reveal mechanisms of synaptic dysfunction in models of neuronal demise and open new research lines on mechanisms of synaptic plasticity.
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.55M | Year: 2015
MASSTRPLAN will train the next generation of interdisciplinary research leaders in advanced molecular analytical techniques to detect oxidized phospholipids & proteins in biological & clinical samples, evaluate their biochemical roles in inflammation, and translate these findings to develop new diagnostic tools. Chronic inflammatory diseases such as diabetes, cardiovascular disease (CVD) & cancer are major causes of mortality and cost the EU economy dearly in healthcare and lost working time; CVD alone is estimated to be responsible for 47% of deaths and to cost the EU 196 billion a year. Scientists able to develop advanced analytical tools for detecting oxidative biomolecule modifications and assessing their contribution to cell dysfunction & disease are urgently needed. The objectives of MASSTRPLAN are to 1) train early stage researchers (ESRs) in advanced and novel chromatography, mass spectrometry, and complementary techniques including microscopy and bioinformatics to detect challenging heterogeneous biomolecule modifications and determine their functional effects; 2) give ESRs a broad perspective on relevance & mechanisms of oxidative modifications in pathophysiology and biotechnology; 3) enable ESRs trained in technology development to engage effectively with the clinical sector; and 4) train ESRs in translational and development skills to produce new protocols, materials and commercializable diagnostic tools. The ETN will achieve this by bringing together 10 beneficiaries and 15 partners from academic, industrial and healthcare organizations working in analytical, bioinformatic, biological, clinical & biotech fields to provide multidisciplinary, cross-sector training. Extensive mobility, industrial secondments and network-wide training will yield a cohort of analytical scientists with the unique theoretical, technological, and entrepreneurial skill set to yield new understanding of oxidative inflammatory disorders, leading to better tools and therapies.
Lamkanfi M.,VIB |
Lamkanfi M.,Ghent University |
Cell | Year: 2014
Recent studies have offered a glimpse into the sophisticated mechanisms by which inflammasomes respond to danger and promote secretion of interleukin (IL)-1β and IL-18. Activation of caspases 1 and 11 in canonical and noncanonical inflammasomes, respectively, also protects against infection by triggering pyroptosis, a proinflammatory and lytic mode of cell death. The therapeutic potential of inhibiting these proinflammatory caspases in infectious and autoimmune diseases is raised by the successful deployment of anti-IL-1 therapies to control autoinflammatory diseases associated with aberrant inflammasome signaling. This Review summarizes recent insights into inflammasome biology and discusses the questions that remain in the field. © 2014 Elsevier Inc.
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.79M | Year: 2015
Algal aquaculture is developing exponentially worldwide, with multiple applications in the food, chemical and pharmaceutical industries. Current research in algal biotechnology mostly focuses on metabolite discovery, aquaculture yield improvement and engineering bottlenecks. However, agronomical experience shows that controlling the interaction of land crops with mutualistic or pathogenic microbes is most critical to successful production. Likewise, controlling the microbial flora associated with algae (the algal microbiome) is emerging as the biggest biological challenge for their increased usage. Bacteria can control the morphogenesis of algae, while others are indispensable to algal survival. Pathogens are causing devastating diseases, the impact of which worsens with the intensification of aquaculture practices. Thus, the overarching aim of ALFF is to train 15 ESRs (researchers and technologists) within a multinational consortium, whilst bringing a scientific step-change in our understanding of these interactions, leading to the development of superior mass algal cultivation and biocontrol strategies. ALFF tackles: 1) the identification, taxonomy and utilisation of naturally-occurring algal symbionts and pathogens; 2) inter- and intra-species signalling and chemical ecology in aquaculture, natural environment and simplified systems (i.e. axenic cultures \/- symbionts); 3) and harnesses state of the art genomics, molecular, and biochemical techniques to characterise these interactions. A highly interdisciplinary team underpins an ambitious theoretical, field, hands-on training and research program. With the support of high profile institutions, ALFF foresees an exceptionally broad range of dissemination and outreach initiatives to help policy makers and the general public better understand the opportunities and issues relating to the sustainable use of our aquatic freshwater and marine resources, within and beyond the EU.