This research aims to harness ultrasonication as innovative thermal treatment tool to effectively engineer the electronic structures of colloidal particles. The main objectives of this project are: 1) to develop various interfacial strategies to establish a general and innovative low cost ultrasonication based thermal treatment protocol; 2) to gain novel and effective sono-engineering methodologies for introducing intrinsic/extrinsic defects in seminconductor nanoparticles; and 3) to acquire innovatively enhanced photovoltaic behaviors of from the sono-engineered semiconductor nanostructures. The anticipated thermal treatment will be easy, cheap, easily accessible, and feasible for massive production in comparison with conventional black-body-radiation-based thermal treatment. This will enable one to gain in-depth insight to the physics of acoustic bubbles and especially the energy release during bubble collapse and to effectively transform existing semiconductor particles to be photovoltaic and photoelectrochemical more active for efficient storage and conversion of solar energy and exploitation, thus making a significant step forwards in solar energy exploitation. The proposed project is a multidisciplinary one, and the results of the project can be of great interest for scientists and engineers from diverse areas including colloids and interface science, material science, nanotechnology, condensed matter physics, sonochemistry, electrochemisty and photovoltaics. According to the project objectives, the proposed project contributes to the 'Nanosciences, Nanotechnologies, Materials and new Production Technologies (NMP)', one of the themes of the 7th European Framework Cooperation Programme. Successfully carrying out of this project will result in significant economic, environmental and strategic impact to energy industry and our sustainable society.

Thermoelectric (TE) materials are of considerable interest because they can convert waste heat to useful electrical energy and will contribute to reducing the global energy crisis. They have been successfully applied to power generation from exhaust heat of automobiles, and have many other potential commercial applications. To realize such applications, TE materials are required that have not only good TE properties, but are also low cost, environmentally friendly, thermally stable and oxidation resistant. Oxide ceramics meet these criteria. Among the large family of oxides, the layered perovskite-related oxides with low lattice thermal conductivity due to the layered structure and possibly high power factor due to the transition metal-oxygen octahedral networks are promising high performance TE materials. So in this proposal AE-Nb-O (AE=alkali earth metals Ca, Sr or Ba) based layered perovskite-related oxides are considered, and their TE properties will be evaluated and improved by using multidisciplinary approaches, including theoretical screening for high TE performance materials, spark plasma sintering of the highly textured ceramics picked out by screening, doping to optimize the TE properties, modeling of the nanosheets containing ceramic composites to utilize the low dimensional effects, and spark plasma sintering of the composites with optimal parameters for high TE performance. The idea of the nanosheets containing ceramic composites is particularly novel and has not been previously reported, and the whole research involves several state of the art concepts and techniques in the TE field and materials science. The main objective is to develop TE oxide with zT>1 above 800K, which corresponds to a heat-to-electricity conversion efficiency greater than 10%, while at the same time improving the understanding of the underpinning physics. This work could make a highly original and significant contribution to the TE field and materials science.

Modulation of leukocyte adhesiveness is critical to leukocyte function during the immune response. In order to extravasate from the blood stream, leukocyte rolling must be followed by integrin-mediated rapid arrest. Intergins play a crucial role on chemokine-induced arrest of leukocytes on blood vessels. Signaling events mediating adhesion are extensively studied. Increasing evidence underlays the essential role of lipid second messenger as important fine regulators of signaling cascade leading to integrin affinity modulation. To date, no technology has ever been developed to monitor intracellular production and localization of specific lipids in the context of leukocyte recruitment. Imaging of small molecules in real time in living cells is usually accomplished with genetically encoded sensors, which are typically fluorescent proteins flanking a ligand-binding domain. However, sensor development is difficult since proteins undergoing conformational changes upon binding a desired target molecule are minimally available. In this scenario, my project aims to produce sensors for fluorescence imaging of small molecules using RNA. These RNA-based sensors comprise a ligand-binding RNA aptamer and Spinach, an aptamer that binds and switches on the fluorescence of a small- molecule fluorophore allowing imaging of the dynamic changes and cell-to-cell variation in the intracellular levels of phosphatidic acid (PA) and phosphatidil-inositol-4,5-biphospate (PIP4,5P2). This tool could be the first of this kind and could be useful to study many aspects of signaling cascade events, not only for leukocyte recruitments. By using lipid Nano-Biosensor I could be able to make FRET and FRAP studies in order to obtain in vivo qualitative and quantitative data allowing topological and dynamic reconstruction of signaling networks. Moreover lipid Nano-Biosensors could be developed as innovative new markers for cell sorting in FACS and in ImageStream Technology.

Besides its function as a passive cell wall plasma membrane (PM), involved in signal transduction and cell adhesion, is essential to enable the formation of tissues. Understanding PM function requires molecular insights into its dynamic spatial organization. Recent studies show that membrane proteins rearrange laterally forming nanoclusters of various size. On the other hand, a hierarchical model of two dimensional PM organization has been proposed including transient confinement in membrane-actin-skeleton induced compartments and lipid rafts. However, an overall picture of the dynamic spatial organization of the PM requires the inclusion of protein trafficking since membrane proteins undergo a constitutive turnover transported in vesicles as cargo from and to the cytosol. The hypothesis of this project is that vesicle trafficking to and from the PM is responsible for the observation of nanoclusters in the PM. Due to the diffraction barrier it is impossible to image nanoclusters with conventional fluorescence microscopy. To avoid this limitation, I will use super-resolution fluorescence imaging methods such as direct Stochastic Optical Reconstruction Microscopy (dSTORM) and Photoactivated Localization Microscopy (PALM) combined with novel statistical cluster analysis to study quantitatively the dynamic reorganization of PM induced by protein trafficking, as well as the role played by actin-skeleton-induced compartments and lipid rafts during this process. I will apply this approach to study a wide family of membrane proteins involved in signal transduction and cell adhesion essential for embryogenesis, neurogenesis, and immune response. The outcome of the project is expected to provide fundamental new insights into PM architecture and organization including protein turnover. Since membrane proteins are one of the most attractive drug targets because they control the communication of cells with their environment, the results will be of high medical significance.

The superlative properties of diamond make it a choice material for making nanoscale devices over a broad range of applications. Diamond devices are conventionally made using 'top-down' processing following the seeding and growth of nanocrystalline diamond thin films, however, due to the great resilience of diamond, fabricating nanoscale devices is technologically demanding and nanoscale patterning requires expensive and lengthy processing such as electron beam lithography (EBL). Herein, the applicant presents a proposal to develop a novel, inexpensive, rapid and scalable methodology to fabricate nanoscale devices using 'bottom-up' processing with a feature resolution that will surpass current state-of-the-art processing techniques such as EBL. To achieve this goal, the technique of DNA Nanotechnology will be used to create self-assembled 2D DNA patterns of any desired shape, which will subsequently be electrostatically and covalently coated with nanodiamond and diamondoid particles. Following diamond seeding on DNA templates, the applicant proposes to grow nanocrystalline diamond thin film devices with nanoscale features. Given the diameter of DNA is ca. 2 nm, structures with nearly 2 nm feature resolution should be achievable, especially when seeding the structures with molecular diamondoid particles. Following development of said technique, nanoscale diamond devices (specifically nanophotonic structures, transistors and biosensors) will be fabricated that promise unprecedented performance.

Molecular imprinted polymers and electrospun nanofibres are both hot topics individually in the biomedical sciences, with applications including tissue engineering, regenerative medicine, drug release, affinity chromatography and biosensors. This proposal combines these two leading-edge approaches to generate entirely novel materials with broad utility in biomedical engineering. Molecular imprinting is a form of template assisted synthesis that facilitates the creation of artificial receptors that can have affinity constants as high as their natural counterparts. Electrospinning (ES) is one of the most broadly used techniques for fabrication of nanostructured materials. ES uses electrical forces to produce continuous fibres having diameters in range of few nanometers to several micrometers. ES offers several technical advantages such as extremely high surface area per unit volume, tunable porosity, flexibility for adapting it to different shapes and sizes, and possibilities for controlling nanofibre composition. In this proposal, we have focused on next generation molecular imprinting using reactive electrospinning to obtain directly imprinted nanofibres. We will demonstrate the utility of this new nanofabrication technology in three key areas: active agent carriers in regenerative medicine, affinity depleting membranes in blood-related proteomics, and biorecognition elements for biosensors. The multidisciplinary nature of the project will make important contributions to the development and validation of new therapies, sustainable and efficient healthcare systems, and strengthening the competitiveness and innovative capacity of European health-related industries. We will be working at the frontiers of two leading research areas having the potential to attract the attention of the researcher community not only in Europe, but also world wide, and to make significant contribution to EU's research priorities, sustainable development and scientific competencies.

This programme will employ physical sciences and biomedicine techniques to develop a revolutionary approach to early cancer diagnosis and post-treatment monitoring aiming to address shortcomings in our current technology in oxygen sensing and imaging of hypoxic prostate tumours. This proposal represents a gearing process towards the biomedical implementation of metal complexes and functionalised nanoparticles as novel synthetic platform systems for personalised diagnosis and treatment of diseases such as cancer and which can also be extended to neurodegenerative disorders. The work programme is a meeting point for interdisciplinary science that goes well beyond state of the art. New chemical sensing devices will outstrip and supersede existing biopsy and imaging techniques used in diagnosis and treatment of diseases such as cancers. The key advances of this programme will be: (a) 'smart' all-in-one multimodal imaging probes, whose sensitivities to levels of oxygen in cells (pO2) will be tunable to respond to various levels of hypoxia in tumors as desired. Our ultra-sensitive probes will be effective at low O2 concentrations and respond to reduced levels of hypoxia and under anoxia. This will surpass the mainstay in cancer diagnosis and therapy and provide increased selectivity for a wider range of tumours. (b) new probes suitable for interlocked Positron Emission Tomography (PET), Single Photon Emission Tomography (SPECT), and optical imaging methodologies Simultaneous in vitro and in vivo diagnostic information from radioimaging techniques (PET, SPECT) and optical imaging will provide in depth understanding of biological processes and lead to personalised medicine. (c) new imaging tools for the first time will monitor the cellular biolocalisation of these probes by multiphoton optical imaging in nearIR regimes. These will drive the development of time-gated microscopy and multi-photon imaging with sensitivity for various levels of tumour hypoxia.

Accurately copying its whole genome is perhaps the most important task of the cell. Mistakes in DNA replication can result in cell death or, potentially worse, in mutagenesis and genomic instability, which in turn can lead to uncontrolled proliferation, the basis of cancer. Elucidating the factors involved in DNA replication and understanding the mechanisms by which human cells guarantee the precise duplication of billions of base pairs and thereby appropriate proliferation are of utmost importance when aiming at defeating several diseases, among which cancer stands out as one of the leading causes of death in the world. While the actual enzymatic activity of DNA synthesis is accomplished by DNA polymerases, a remarkable set of extra factors is required for replication within the cell. Though the core replication components seem to be conserved from yeast to humans, in mammals the putative homologues of several key factors likely act with different mechanisms or have additional functions, as suggested by the low homology level and presence of extra domains. Thus, the object of my proposal is to identify novel factors involved in normal DNA replication progression and the response to replicative stress at the replisome level, specifically in human cells. I will put additional emphasis on elucidating the function of known metazoan-specific factors, which likely play a key role in the complex regulatory mechanisms required in higher organisms. To this end, I will combine various cutting edge methods, like nanobody-based sequential purifications, SILAC mass spectrometry and 3D-SIM microscopy, to develop assays to isolate active replisomes from human cells and study the identified factors mechanistically. This strategy will allow me to exploit and significantly expand my technical expertise and, complemented by the selected world-class host scientist and institute, to grow into an independent scientist and enhance Europe's research excellence.

Nanowires are a powerful and versatile platform for a broad range of applications. Among all semiconductors, the heavy-elements materials exhibit the highest electron mobilities, strongest spin-orbit coupling and best thermoelectric properties. Nonetheless, heavy-element nanowires have been unexplored. With this proposal we unite the unique advantages of design freedom of nanowires with the special properties of heavy-element semiconductors. We specifically reveal the potential of heavy-element nanowires in the areas of thermoelectrics, and topological insulators. Using our strong track record in this area, we will pioneer the synthesis of this new class of materials and study their intrinsic materials properties. Starting point are nanowires of InSb and PbTe grown using the vapor-liquid-solid mechanism. Our aims are 1) to obtain highest-possible electron mobilities for these bottom-up fabricated materials by investigating new materials combinations of different semiconductor classes to effectively passivate the nanowire surface and we will eliminate impurities; 2) to investigate and optimize thermoelectric properties by developing advanced superlattice and core/shell nanowire structures where electronic and phononic transport is decoupled; and 3) to fabricate high-quality planar nanowire networks, which enable four-point electronic transport measurements and allow precisely determining carrier concentration and mobility. Besides the fundamentally interesting materials science, the heavy-element nanowires will have major impact on the fields of renewable energy, new (quasi) particles and quantum information processing. Recently, the first signatures of Majorana fermions have been observed in our InSb nanowires. With the proposed nanowire networks the special properties of this recently discovered particle can be tested for the first time.

Developing sustainable solar energy technology becomes extremely important to secure our energy future. A highly novel solar thermal technology, from both nanotechnology and phase change approaches, is proposed in this project to address the limitations associated with conventional solar thermal collectors. In this innovative technology, direct absorption nanoparticles are used to overcome the surface-controlled heat transfer limitation and absorb solar energy directly in the carrying fluid, and oscillating vapour bubbles (in oscillating heat pipes) are used to drive the fluids instead of pumps. Preliminary studies have shown the feasibility of the new concept, which has both prosperous scientific and applicaton propsects. Scientifically, it extends the direct absorption nanoparticles into a phase change domain, and practically it could promote the emergence of a new generation of solar collector. A systematic program is proposed in this project to address the challenges associated with the novel concept, which extends from suitable direct absorption nanofluid formulation, understanding the role of nanoparticles in the evaporation and condensation process, to its performance in ossillating heat pipes. The project is an ambitious, highly novel piece of work ideally suited to a Fellow with a strong background in solar energy and thermal science and engineering. The Fellow in question, Dr Lizhan Bai is perfectly (perhaps uniquely) suited to drive this project to success as he has independently designed, constructed and experimented with a number of challenging flow and heat transfer devices, especially heat pipe systems, and has outstanding analytical and mathematical modelling capability, which will contribute uniquely to the project. It will allow significant knowledge transfer into Europe, especially heat pipe systems, and create potentials long term collaborations and mutually beneficial co-operation between Europe and China.