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UCPH

KOBENHAVNS UNIVERSITET
Country: Denmark
689 Projects, page 1 of 138
  • Funder: EC Project Code: 798716
    Overall Budget: 200,195 EURFunder Contribution: 200,195 EUR

    Around 90% of all cancer-related deaths are due to metastasis. Understanding the process of cancer metastasis is therefore of urgent need to develop new treatments. Aberrant expression of the epidermal growth factor receptor (EGFR), or increased availability of its ligands promote tumour survival and metastasis in multiple cancers. As a result, several anti-EGFR therapeutics are in clinical use, but almost all patients will develop resistance against the treatment. Another strategy to treat EGFR driven cancers is to reduce the pool of available EGFR ligands. The crucial enzyme in EGFR ligand release is A Disintegrin And Metalloproteinase (ADAM) 17. I have unpublished data showing that depletion of ADAM17 significantly inhibits colon cancer growth and metastasis in vivo. However, anti-ADAM17 therapies have failed clinically and thus, we urgently need to understand the regulation of ADAM17. Recent discoveries by Dr. Kveiborg’s group, and collaborators showed that the protein phosphatase PP2A binds to ADAM17, and negatively regulates EGFR ligand release, thereby representing the first known negative regulator for ADAM17. Based on these novel findings, I hypothesize that the PP2A-ADAM17-EGFR axis has the ability to control cancer metastasis. To test this hypothesis, I aim to characterize the functional impact of the PP2A-ADAM17 interaction in cancer spread by creating ADAM17 mutants with different PP2A binding properties in colon cancer cells using CRISPR/Cas9 and functionally evaluate these cells in vitro and in zebrafish and mouse models. Moreover, I aim to unravel the molecular mechanisms of the interplay; applying SILAC coupled mass spectrometry and mutagenesis screening, to evaluate the mechanism by which PP2A affects ADAM17, and the signals involved in PP2A binding. This work will pave the way for the development of novel anti-cancer drugs and thereby expand the therapeutic choices for EGFR driven cancers and improve the patient survival.

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  • Funder: EC Project Code: 841910
    Overall Budget: 219,312 EURFunder Contribution: 219,312 EUR

    Coastal seagrass ecosystems provide important services to nature and mankind in form of coastal protection, nursery grounds and carbon sequestration. However, seagrass meadows are affected by global climate change and anthropogenic stressors such as eutrophication and coastal development. Yet, the mechanistic interactions between these ecosystems and environmental change remain unclear due to the complexity of studying the seagrass habitat, which exhibit a multitude of chemical gradients and dynamics. The requirement for high-resolution measurement techniques for resolving the biogeochemical dynamics and microenvironments surrounding seagrasses in their natural habitat has led to the development of a variety of chemical techniques typically quantifying a single analyte at a time, which gives limited insight to the true dynamics of the seagrass-sediment interaction which is central for seagrass fitness and survival under environmental change. The SIPODET project will develop new multi-parameter chemical imaging techniques by combining luminescence-based optical sensor foils (planar optodes) with diffusional equilibrium in thin-film (DET) enabling simultaneous sensing of pO2, iron, phosphate, nitrite/nitrate, ammonium, manganese, pCO2 and pH. This project will encompass expert training of Dr. Cesbron in the use of planar optodes complementing his expertise in 2D DET mapping of chemical species, which will enable the development of a novel combined chemical imaging technology mentored by a world leader in microenvironmental analysis. The novel technology will investigate the dynamic chemical microenvironment in the seagrass rhizosphere and how this is modulated by environmental change and plant stress (e.g. effects of temperature, pH or eutrophication) in Zostera marina and Zostera noltei.

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  • Funder: EC Project Code: 101023584
    Overall Budget: 219,312 EURFunder Contribution: 219,312 EUR

    Prolines are unique amongst aminoacids given that they naturally exist in two isomeric states: CIS and TRANS. The transition between these states is slow but can be catalyzed by the activity of proline isomerases such as PIN1. Recent in vitro work suggests that PIN1 can alter the phosphorylation dynamics of the C-terminal domain (CTD) of RNA polymerase II (Pol II) by inhibiting phosphatase recognition. Given Pol II is solely responsible for transcribing all protein-coding genes and that CTD phosphorylation dictates the timing of RNA co-transcriptional processes, these observations suggest a crucial role for CTD proline isomerization in gene expression. Importantly, mutations in PIN1 are associated with cancer progression but a direct role for proline isomerization has remained understudied given the technical limitations imposed by its complex enzymology, such as the inability of differentiating CIS and TRANS isomers using Mass Spectrometry. In this project, I aim to functionally dissect the role of proline isomerization during Pol II transcription using rigorous biochemical, cellular and genomic techniques. Specifically, I will exploit new technological advances in peptide synthesis to permanently “lock” prolines in CIS or TRANS and identify novel isomer-specific interacting factors. I will systematically examine the consequences of CTD proline mutations and of rapid depletion of PIN1 in human cells, focusing on CTD-dependent co-transcriptional RNA processes such as splicing and poly-A–dependent 3’ termination. At the basic research level, my results will provide unprecedented resolution to the dynamics of Pol II phosphorylation, which underlies regulation of gene expression in multicellular organisms. Translationally, given that various cancers hijack the transcriptional programmes of the cell, this mechanistic understanding of CTD proline isomerization will better equip future clinical studies interested in the yet-to-be-characterized role of PIN1 in oncogenesis.

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  • Funder: EC Project Code: 749316
    Overall Budget: 200,195 EURFunder Contribution: 200,195 EUR

    The quantum revolution is happening now. Every day experimentalists around the world produce more complex, reliable and powerful quantum devices which take us one step closer to quantum computation, communication and cryptography. Testing is a crucial part of the development process necessary to ensure suitability of the device for the application in mind. Methods used for small devices quickly become impractical, as the devices become more complex and we need to develop efficient and robust testing procedures in order to make further progress. Fortunately, quantum physics is well-suited for this task, as it allows to precisely characterise devices under surprisingly weak assumptions. This feature, known as self-testing, is intrinsically related to the fundamental concept of Bell inequalities. The goal of this proposal is to develop efficient and robust testing procedures for complex quantum devices based on Bell's theorem. In the short-term these will allow experimentalists to efficiently characterise their devices, while in the long-term they will enable a customer to certify that a newly bought quantum device adheres to the specification, which opens the door to device-independent information processing. The timeliness of this proposal is demonstrated by the fact that the first loophole-free Bell experiments were reported within the last year. On top of practical applications, self-testing is important from the foundational point of view. By exploring the intimate connection between the quantum (microscopic) world of Hilbert spaces and the classical (macroscopic) world of resulting probability distributions, it provides the unique link between what we see and what is happening at the quantum level. This fellowship will allow Jędrzej Kaniewski to work under the supervision of Matthias Christandl (a world-class expert on quantum correlations) at the University of Copenhagen (a leading institution in both theoretical and experimental aspects of quantum mechanics).

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  • Funder: EC Project Code: 895909
    Overall Budget: 207,312 EURFunder Contribution: 207,312 EUR

    In the wake of violence, dispossession, and regime change, giving back land offers a critical opportunity to address historic injustice. Yet seeking to reconcile the past invites conflicts over material distribution and political inclusion in the nation’s future. This project investigates land restitution in Myanmar, a formerly authoritarian, predominantly agrarian nation currently undergoing a rapid, public and bumpy transition towards democracy. Building on over five years of research on land reform and agrarian change in Myanmar, I ask how the new government’s efforts to return land are taking shape, and what these processes mean for the nation’s future and for the place of rural land in global development. Under the guidance of Prof. Christian Lund, a leading scholar on the production of property and citizenship in developing societies, this project will contribute new empirical analysis, conceptual insights, and policy recommendations to inform urgent debates on rural transformation, democratization and social inequality.

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