ERC FUNDED PROJECTS

Cytokinesis completes cell division by partitioning the contents of the mother cell to the two daughter cells. This process is accomplished through the assembly and constriction of a contractile ring, a complex actomyosin network that remains poorly understood on the molecular level. Research in cytokinesis has overwhelmingly focused on signaling mechanisms that dictate when and where the contractile ring is assembled. By contrast, the research I propose here addresses fundamental questions about the structural and functional properties of the contractile ring itself. We will use the nematode C. elegans to exploit the power of quantitative live imaging assays in an experimentally tractable metazoan organism. The early C. elegans embryo is uniquely suited to the study of the contractile ring, as cells dividing perpendicularly to the imaging plane provide a full end-on view of the contractile ring throughout constriction. This greatly facilitates accurate measurements of constriction kinetics, ring width and thickness, and levels as well as dynamics of fluorescently-tagged contractile ring components. Combining image-based assays with powerful molecular replacement technology for structure-function studies, we will 1) determine the contribution of branched and non-branched actin filament populations to contractile ring formation; 2) explore its ultra-structural organization in collaboration with a world expert in electron microcopy; 3) investigate how the contractile ring network is dynamically remodeled during constriction with the help of a novel laser microsurgery assay that has uncovered a remarkably robust ring repair mechanism; and 4) use a targeted RNAi screen and phenotype profiling to identify new components of actomyosin contractile networks. The results from this interdisciplinary project will significantly enhance our mechanistic understanding of cytokinesis and other cellular processes that involve actomyosin-based contractility.

1 499 989 €

Start date: 2015-07-01, End date: 2020-06-30

This project will develop the principles required to enable bond-modifying redox catalysis based on aluminium by preparing and studying new Al(I) compounds capable of reversible oxidative addition. Catalytic processes are involved in the synthesis of 75 % of all industrially produced chemicals, but most catalysts involved are based on precious metals such as rhodium, palladium or platinum. These metals are expensive and their supply limited and unstable; there is a significant need to develop the chemistry of non-precious metals as alternatives. On toxicity and abundance alone, aluminium is an attractive candidate. Furthermore, recent work, including in our group, has demonstrated that Al(I) compounds can perform a key step in catalytic cycles - the oxidative addition of E-H bonds. In order to realise the significant potential of Al(I) for transition-metal style catalysis we urgently need to: - establish the principles governing oxidative addition and reductive elimination reactivity in aluminium systems. - know how the reactivity of Al(I) compounds can be controlled by varying properties of ligand frameworks. - understand the onward reactivity of oxidative addition products of Al(I) to enable applications in catalysis. In this project we will: - Study mechanisms of oxidative addition and reductive elimination of a range of synthetically relevant bonds at Al(I) centres, establishing the principles governing this fundamental reactivity. - Develop new ligand frameworks to support of Al(I) centres and evaluate the effect of the ligand on oxidative addition/reductive elimination at Al centres. - Investigate methods for Al-mediated functionalisation of organic compounds by exploring the reactivity of E-H oxidative addition products with unsaturated organic compounds.

1 493 679 €

Start date: 2017-03-01, End date: 2022-02-28

Since 2012, over 4 million people have fled Syria in ‘the most dramatic humanitarian crisis that we have ever faced’ (UNHCR). By November 2015 there were 1,078,338 refugees from Syria in Lebanon, 630,776 in Jordan and 2,181,293 in Turkey. Humanitarian agencies and donor states from both the global North and the global South have funded and implemented aid programmes, and yet commentators have argued that civil society groups from the global South are the most significant actors supporting refugees in Lebanon, Jordan and Turkey. Whilst they are highly significant responses, however, major gaps in knowledge remain regarding the motivations, nature and implications of Southern-led responses to conflict-induced displacement. This project draws on multi-sited ethnographic and participatory research with refugees from Syria and their aid providers in Lebanon, Jordan and Turkey to critically examine why, how and with what effect actors from the South have responded to the displacement of refugees from Syria. The main research aims are: 1. identifying diverse models of Southern-led responses to conflict-induced displacement, 2. examining the (un)official motivations, nature and implications of Southern-led responses, 3. examining refugees’ experiences and perceptions of Southern-led responses, 4. exploring diverse Southern and Northern actors’ perceptions of Southern-led responses, 5. tracing the implications of Southern-led initiatives for humanitarian theory and practice. Based on a critical theoretical framework inspired by post-colonial and feminist approaches, the project contributes to theories of humanitarianism and debates regarding donor-recipient relations and refugees’ agency in displacement situations. It will also inform the development of policies to most appropriately address refugees’ needs and rights. This highly topical and innovative project thus has far-reaching implications for refugees and local communities, academics, policy-makers and practitioners.

1 498 069 €

Start date: 2017-07-01, End date: 2022-06-30

The phytohormone auxin has profound importance for plant development. The extracellular AUXIN BINDING PROTEIN1 (ABP1) and the nuclear AUXIN F-BOX PROTEINs (TIR1/AFBs) auxin receptors perceive fast, non-genomic and slow, genomic auxin responses, respectively. Despite the fact that ABP1 mainly localizes to the endoplasmic reticulum (ER), until now it has been proposed to be active only in the extracellular matrix (reviewed in Sauer and Kleine-Vehn, 2011). Just recently, ABP1 function was also linked to genomic responses, modulating TIR1/AFB-dependent processes (Tromas et al., 2013). Intriguingly, the genomic effect of ABP1 appears to be at least partially independent of the endogenous auxin indole 3-acetic acid (IAA) (Paque et al., 2014). In this proposal my main research objective is to unravel the importance of the ER for genomic auxin responses. The PIN-LIKES (PILS) putative carriers for auxinic compounds also localize to the ER and determine the cellular sensitivity to auxin. PILS5 gain-of-function reduces canonical auxin signaling (Barbez et al., 2012) and phenocopies abp1 knock down lines (Barbez et al., 2012, Paque et al., 2014). Accordingly, a PILS-dependent substrate could be a negative regulator of ABP1 function in the ER. Based on our unpublished data, an IAA metabolite could play a role in ABP1-dependent processes in the ER, possibly providing feedback on the canonical nuclear IAA-signaling. I hypothesize that the genomic auxin response may be an integration of auxin- and auxin-metabolite-dependent nuclear and ER localized signaling, respectively. This proposed project aims to characterize a novel auxin-signaling paradigm in plants. We will employ state of the art interdisciplinary (biochemical, biophysical, computational modeling, molecular, and genetic) methods to assess the projected research. The identification of the proposed auxin conjugate-dependent signal could have far reaching plant developmental and biotechnological importance.

1 441 125 €

Start date: 2015-06-01, End date: 2020-05-31