Individual projects Archives - ITN SNAL - Marie Curie Initial Training Network

Association of polymers and small solute molecules with phospholipid membranes

Yachong Guo — Mon, 13 Oct 2014 12:48:32 +0000

Theoretical physics, theory in soft matter, computer simulations Objectives In many cases the properties of cell membranes are modified through biopolymers and small solute molecules such as anesthetics or neurotransmitters. They can associate to membranes and significantly alter their structure, either thermodynamic state or induce reorganization in form of pores. The project aims to describe the fundamental controls of these processes that trigger such membrane modification or structural reorganization using the Single Chain Mean Field (SCMF) theory. Tasks and methodology Implementation of a hybrid Single Chain Mean Field theory with Monte Carlo simulations Construction of the models for polymer – bilayer

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Investigation and characterization of RNA-loaded liposome vaccines

Sat, 11 Oct 2014 20:32:53 +0000

Experimental methods and characterisation techniques Description We have previously demonstrated that certain combinations of lipids within a liposome formulation enable the highly effective delivery of RNA liposome vaccines to cells. However, such formulations have to date only been prepared at laboratory scale and methods are required whereby they can be manufactured in sufficient quantities for clinical trials and eventual marketing. Such methods must enable the formulation of RNA in high yield, due to the high cost of both the active ingredient and the lipids involved in the formulation, and result in a thermally stable formulation in which liposomes neither agglomerate

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ER2-B: Investigation of membrane permeating materials in biostabilisation

Martin Stefanic — Thu, 05 Dec 2013 15:53:59 +0000

Experimental methods and characterisation techniques in cell preservation and biostabilisation Objectives Evaluate how size, shape and physical nature (net charge, pH responsiveness and nanoparticle and CNT characteristics) affect their interaction with membranes. These studies aim to link transfection efficiency from different therapeutic models (size, charge and proteins versus DNA) with the structural design of the therapeutic nanoparticles, and to shed more light on the toxicity of such substances in general. Tasks and methodology Testing new pH-responsive synthetic polymers (from Cambridge) to deliver (chemo-)biotherapeutics and stabilisers to the cell cytoplasm by disrupting endosomal membranes, which are used for cell preservation technology.

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ER1-U: Delivery of skin bioactives to assess the impact of membrane lytic biopolymers

Radka Petkova — Thu, 05 Dec 2013 15:50:13 +0000

Impact of membrane lytic biopolymers on skin lipid membranes Contact Radka Petkova Objectives Exploration of the possibilities in obtaining of end product and involvement of the private sector in the training program. Exploring opportunities to implement the findings from different work programs into product relevant system; Identify potential gaps in the available toolbox for studying nano-object interactions with membrane lipid bi-layers and recommend way addressing those. Tasks and methodology By utilising both the research expertise and capabilities at Unilever to implement the learning from the program to date and try to create a prototype with improved delivery of benefit agents/active to

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ESR11-F: Delivery of molecular payloads through primary human cell membrane

André Dias — Thu, 05 Dec 2013 15:44:08 +0000

In-vitro experiments on living cells, toxicology studies Contact Andre Dias Objectives The goal is to compare and validate the synthetic lipid models to biologically relevant cell types and to investigate how different nano-objects interact with representative lipid single and bilayers compared to human cells with and without therapeutic incorporation. Tasks and methodology Cellular uptake of fluorescence-labelled nano-complexes will be checked by Delta Vision High Resolution microscopy and with an accompanied immunofluorescence counter-staining for intracellular organelles to identify distinct cellular endocytotic routes such as clathrin- or caveolae-dependent mechanisms or intracellular dispositions of the nanoparticles. Nanoparticles will be applied to the upper

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ESR12-F: Toxicity of nano-objects on human cells models

Anna Orlowska — Thu, 05 Dec 2013 15:40:48 +0000

In-vitro experiments on living cells, toxicology studies Contact Anna Orlowska Objectives Main objective is to compare, validate and corroborate the findings of the interaction of the nano-objects synthesised by the network to actual human cell models with the findings observed with the lipid membrane model systems. Tasks and methodology Recruited ESR will obtain experience in toxicity, cell- and molecular biological methodology and will be able to carry out toxicological evaluation of material, their attachment to, uptake or translocation across cells or barrier models. After nanomaterial exposure cell viability will be evaluated by standardized MTS-assay and the cellular membrane integrity of

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ESR10-C: Bioengineering of membrane associating polymers and polymer-protein complexes

Alex Chen — Thu, 05 Dec 2013 15:19:55 +0000

Investigation of membrane associating polymers, therapeutic nanoparticles and cell preservation experiments Biotechnology and and bioengineering, experimental Contact Alex Chen Objectives A safe polymer technology, which can be fine-tuned to deliver a wide variety of payloads into cells for various applications. Novel pH-responsive, biodegradable polymers will be synthesized to mimic the activity of viruses, both in their cell entry and endosomal escape mechanisms Synthesis of functional polymers and nanoparticles to tailor interactions and permeability of lipid bilayers for biomedical applications. Tasks and methodology Characterisation of the membrane translocation properties of the materials with mammalian cells and with lipid vesicles. Experimental investCelligation

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ESR9-M: Investigation of interaction of membrane-lytic molecules with lipid monolayer

Daniela Ciumac — Thu, 05 Dec 2013 15:14:29 +0000

Supported bilayers and vesicles Objectives The intention of this project is to obtain experimental information and feedback for system improvement of nano-objects interacting with model membranes (supported bilayers and vesicles). to apply a combination of techniques including neutron reflectivity, SANS (Manchester, Unilever), AFM, TEM (Strasbourg, Manchester) to characterise supported lipid bilayers and model vesicles; to investigate how different nano-objects (polymers, block copolymers, short peptide aggregates, CNTs, nanoparticles) interact with lipid bilayers; to undertake selected studies of the interactions with therapeutic complexes to identify the vectors that provide optimal therapeutic delivery with minimal cytotoxicity. Tasks and methodology Interaction of nano-objects with

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ESR7-S: Optical microscopy and microrheology of giant unilamellar vesicles interacting with nano-objects

Mattia Morandi — Thu, 05 Dec 2013 15:09:11 +0000

Experimental investigation of unilamellar vesicles and their dynamics Description Experimental project on the morphological and mechanical changes in lipid vesicles caused by exposure to the nano-objects, by means of epi- and confocal fluorescence studies. Emphasis will be put on understanding the influence of lipid composition, oxidation and investigating the membrane structure changes using ratiometric fluorescent probes. Starting date December 2014 Methods and techniques Related research topics

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ESR8-S: Kinetics of nanoscale structural changes occurring in small unilamellar vesicles

Monika Kluzek — Thu, 05 Dec 2013 15:07:02 +0000

Experimental investigation of unilamellar vesicles using microscopy techniques Contact Monika Kluzek Description Experimental project on small unilamellar lipid vesicles (SUV) interacting with nanoparticles, with special emphasis on the use of transmission electron microscopy (cryo-TEM). This project will consist in elaborating, characterizing and studying in detail decorated liposomes, using state of the art techniques such as EM tomography and time controlled freezing. He/she will become the referent for the electron microscopy platform. Project start July 2014 Related research topics

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