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Prof. Dr. Cornelia Palivan

Department of Chemistry
Profiles & Affiliations

Projects & Collaborations

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BIOINSPIRED MULTIFUNCTIONAL BIO-SYNTHETIC SUPRAMOLECULAR ASSEMBLIES

Research Project  | 1 Project Members

Various domains require materials that integrate emerging properties with multifunctionality to efficiently solve complex issues (e.g. early detection and treatment of severe pathologies, sensing and correction of food quality issues, simultaneous determination of the presence of pollutants in water, biofilm formation). Amongst the most promising strategies is the use of bio-inspired bottom-up approaches based on interfacing biomolecules (enzymes, proteins, DNA) with synthetic assemblies (micelles, vesicles, particles). This combination can produce bio-synthetic materials that surpass conventional systems in terms of efficacy and functionality as they profit from the activity and specificity of the biomolecules whilst the synthetic matrix provides the necessary stability and robustness. The objective of this project is to create bio-inspired multifunctional supramolecular assemblies , in which activation and responses are stimuli-triggered. These multifunctional supramolecular assemblies will serve either as multiplexed reaction spaces at the nanoscale with magnetic controlled propulsion or as active surfaces patterned with responsive nano- assemblies. These directions, connected by biomolecules serving as active components, are inspired by aspects of natural organelles and cells, including signalling pathways, responsiveness and triggered production of molecules. Overall, this interdisciplinary project combines physical chemistry, nanoscience, surface science and enzyme biochemistry. The first subproject plan is to create clusters of active Janus-multicompartments by DNA-mediated self-organization of magnetic Janus nanoparticles and catalytic compartments based on polymersomes equipped with active molecules. Two different types of catalytic nanocompartment will be specifically attached to the lobes of Janus nanoparticles and activated by stimuli present in the environment. The intrinsic activity of the encapsulated molecules inside the catalytic nanocompartments will induce multifunctionality into the clusters, whilst the Janus nanoparticles will serve as "shuttles" to support the directional propulsion of the clusters in the presence of a magnetic field. To demonstrate the potential of the system in photodynamic therapy, we have selected enzymes and photosensitizers, respectively, as model compounds inside each type of catalytic nanocompartments. Clusters of active Janus-multicompartments have the advantages of segregation of protected spaces for active molecules and dual functionality with time, and space precision due to the stimuli-responsive manner of their activation and propulsion. The second subproject aims to construct multifunc tional "active surfaces" by specific immobilization of different types of biomolecule-loaded nano-assembly (peptide nanoparticles and polymersomes) on solid supports. These active surfaces will exhibit dual functionality in the presence of stimuli: polymersomes containing enzymes will act as catalytic nanocompartments for sensing pH changes, whilst peptide nanoparticles will release their cargo upon changes in temperature. A controlled surface pattern will be achieved by combining two approaches for immobilization of nano- assemblies on solid supports: DNA-mediated connection for polymersomes and covalent binding for peptide nanoparticles. To illustrate one of the possible applications, we have selected enzymes and flavonoids for sensing and correcting early changes in food quality. Such active surfaces have several advantages including versatility and modularity of specific patterning and multifunctionality associated with simultaneous responses to external stimuli. Knowledge gained from the fundamental study of the molecular factors, interactions and conditions that are essential to build such multifunctional bio-synthetic assemblies will support their development as efficient platform for solving complex issues in various fields, including medicine, food science, environmental sciences, and technology.

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High Performance Transmission Electron Microscope for Present and Future Nanomaterials

Research Project  | 9 Project Members

The rise of nanoscience and nanotechnology would not have been happened without the impressive development of instruments that allow to resolve structure on the nanometer scale with atomic resolution. Examples are scanning-probe and electron microscopy techniques. In recent years, several major breakthroughs gave rise to an exceptional boost in the performance of today's electron microscopy (EM), both for solid-state and soft (e.g. biological) materials: 1) high-resolution through image corrections, 2) fast and highly efficient electron detectors, 3) efficient artifact-free sample fabrication (cryo-EM and FIBEM), and 4) 3D tomography and image reconstruction. This has given a leap to what can be imaged today, allowing for example to reconstruct the atomic structure of single proteins and image complex interfaces in solid-state materials with atomic scale. The University of Basel (UBAS) is nationally and internationally recognized as a leader in nanoscience and nanotechnology. It was the leading house of the National Center in Competence and Research (NCCR) on Nanoscience, which later became the Swiss Nanoscience Institute (SNI), the institution that submits the current proposal. UBAS is also co-leading the NCCR Molecular Systems Engineering and the NCCR QSIT on Quantum Science (both together with ETHZ). Nanoscience is a focus area in the research portfolio of UBAS and instrumental for the recent development of quantum science. The present proposal to the SNF R'Equip scheme has been put together by key researchers at UBAS who work on current topics in nanoscience and nanotechnology in various disciplines from quantum science, material science, polymer chemistry to molecular biology, and, who make use of EM available within the SNI. The principle investigators, who submit this proposal together, do research that relies on the availability of state-of-the-art nanoimaging tools, such as a transmission electron microscope (TEM). The proposal outlines a convincing case for the purchase of special, unique TEM that combines state-of-the-art (and fast) atomic resolution imaging with material analysis using EDX and scanning TEM (STEM). This combination is unique and crucial for the University of Basel to stay at the forefront of science.

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NCCR MSE: Zipping of Synthetic Assemblies Equipped to Produce Multifunctional Clusters for Bio-Applications

Research Project  | 1 Project Members

This project will develop an innovative methodology to create size controlled polymer clusters of compartments that selectively and stably attach to the surface of epithelial cells. Such compartment clusters will be used to attach to scavenger receptors of the cell membranes and support medical applications. By loading specific compartments with different compounds and them zipping them together, the clusters will achieve multifunctionality serving for the development of nanoteranostics and dual-sensing systems. In addition, such segregated confined spaces at the nanoscale can be used to achieve efficient complex cascade reactions in between compartments.

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NanoGhip - Nano-switchable GPCR-arrestin biochip for drug discovery

Research Project  | 2 Project Members

Our motivation is to overcome key shortcomings of current GPCR lab-on-a-chip nanoscale drug discovery and extend the established and well accepted but limited SPR-based drug screening by new possibilities to address inherently difficult-to-screen GPCRs, and more than that, to obtain detailed functional information about differences of ligands at nanoscale and the biological effects that they trigger for more comprehensive drug profiling. In fact, the need to identify drugs that discriminate between G protein and arrestin signaling has revolutionized GPCR drug discovery setting paradigm shifts and defining "biased agonism" or "functional selectivity". Investment-intense activities can be observed in terms of patent disclosures for new chemical entities with such properties by Biotech, but also large Pharma companies. NanoGhip finds application not only in lab-on-a-chip nanoscale drug screening, but also assists struc-ture-based drug discovery (SBDD), e.g. for determination of ideal crystallization conditions. Of course, NanoGhip could be as well implemented in diagnostic lab-on-a-chip tools to detected overregulated na-tive ligands as indicators of disease on-site.