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CISPA

Helmholtz Center for Information Security
Country: Germany
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81 Projects, page 1 of 17
  • Open Access mandate for Publications and Research data
    Funder: EC Project Code: 793858
    Overall Budget: 159,461 EURFunder Contribution: 159,461 EUR
    Partners: CISPA

    T cell memory is the cornerstone of protective immunity and the key determinant of the efficacy of vaccination approaches. Memory inflation (MI) is a unique type of CD8+ T cell memory characterized by the induction of robust and durable populations of functional effector/effector memory CD8+ T cells that is elicited by latently persistent cytomegalovirus (CMV) infections. Accumulating evidence argues that inflationary T cells can provide exceptionally strong immune protection. Hence, several translational approaches involving MI, such as CMV vector-based vaccines, are subject of ongoing pre-clinical and clinical projects. Despite this, little is known about the cellular and molecular mechanisms governing the induction and maintenance of MI. In this proposal, I aim to identify and characterize the latently infected cell type/-s, which sustain CMV-specific inflationary CD8+ T-cells. To this end, I will combine state-of-the-art stromal cell characterization and isolation techniques with generation of novel recombinant virus-based in vivo models enabling (1) tracking of latently infected cells, (2) conditional ablation of viral peptide processing in selected cell types. The results of this action are expected to improve our understanding of the mechanisms and requirements for MI, laying the basis for the development of improved vaccination strategies. Furthermore, identification of the sites of CMV latency in vivo will have implications for development of future clinical strategies aimed at harnessing the ability of CMV to reactivate in immune suppressed patients. Thus, this proposal explores a basic biological question of broad general interest, but also has robust translational potential for applications in human medicine.

  • Open Access mandate for Publications and Research data
    Funder: EC Project Code: 101024631
    Overall Budget: 174,806 EURFunder Contribution: 174,806 EUR
    Partners: CISPA

    Pseudomonas aeruginosa (PA) is ubiquitous gram-negative bacteria. PA is a serious threat and is considered as a critical priority for treatment development by various institutions such as the World Health Organization. PA can cause infections on various location such as eyes, lung, skin (wounds). Immunocompromised patients are especially at risk, as PA is also able to colonize domestic and hospital fixtures. To add insult to injury, the infection is hard to treat and the number of antibiotic resistant PA is on the rise. The major challenge opposed by PA is its biofilm. Biofilms are a structured bacterial community embedded in a matrix composed of exopolysaccharides, proteins, extracellular DNA, and lipids. PA present in the biofilm are a thousand times less sensitive to antibiotics than their planktonic form. The MONAGEL project propose to fight the PA in the biofilm by developing a hydrogel made of cross-linked lipid nanoparticles. The lipophilic core of the lipid nanoparticles will be used to encapsulate hydrophobic active ingredients, the aqueous cavities of the gel will be used to encapsulate hydrophilic ones. The hydrophobic and hydrophilic compartment will enable work with a broad variety of molecules such as fluorescent probes (which will permit a thorough characterisation of the gel) or active ingredients such as antibiotics and pathoblockers. The latter molecule will be efficient to design the gel towards fighting PA biofilm either by inhibiting quorum sensing (bacterial communication) or lectin interaction (key role in biofilm formation). Well thought work and contingency plans have been put in place to ensure the success of MONAGEL development. The innocuity of the system will be assessed on various cell lines, and the antibiofilm efficacy will be tested on in vitro models. In the end, the MONAGEL efficacy will be demonstrated on a co-culture model (epithelium + biofilm) as a proof-of-concept to serve as a selling point for further development.

  • Funder: EC Project Code: 260934
    Partners: CISPA
  • Open Access mandate for Publications
    Funder: EC Project Code: 716311
    Overall Budget: 1,499,550 EURFunder Contribution: 1,499,550 EUR
    Partners: CISPA

    Bacterial infections are now a global threat demanding novel treatments due to the appearance of resistances against antibiotics at a high pace. The ESKAPE pathogens are those with highest importance in the EU and chronic infections due to biofilm formation are a particular task. Noninvasive pathogen-specific imaging of the infected tissue is not clinically available. Its successful implementation will enable the choice of appropriate therapy and boost efficacy. Furthermore, Gram-negative bacteria have a highly protective cellular envelope as an important resistance mechanism for drugs acting intracellularly, resulting in an alarmingly empty drug-pipeline. To overcome this gap, I will establish Lectin-directed Theranostics targeting pathogens via their extracellular carbohydrate-binding proteins at the site of infection for specific imaging and treatment. This will be implemented for the highly resistant ESKAPE pathogen Pseudomonas aeruginosa through 3 different work packages. WP1 Sweet Imaging: Design & conjugation of lectin-directed ligands to imaging probes, Optimization of ligand/linker, in vivo proof-of-concept imaging study. WP2 Sweet Targeting: Delivery of antibiotics to the infection through covalent linking of lectindirecting groups. Employing different antibiotics, assessment of bactericidal potency and targeting efficiency. Manufacturing of nano-carriers with surface exposed lectin-directed ligands, noncovalent charging with antibiotics. In vitro and in vivo targeting. WP3 Sweet SMART Targeting: Conjugates as SMART drugs: specific release of anti-biofilm lectin inhibitor and drug cargo upon contact with pathogen, development of linkers cleavable by pathogenic enzymes. SWEETBULLETS will establish fundamentally novel lectin-directed theranostics to fight these deleterious infections and provide relief to nosocomially infected and cystic fibrosis patients. It is rapidly extendable towards other ESKAPE pathogens, e.g. Klebsiella spp..