BioNano Interactions: The development of a rational basis for investigating and understanding how nanomaterials interact within living systems (cells, tissues, organisms, humans) is a fundamental challenge for scientists. Understanding the mechanisms and spatiotemporal aspects of nanomaterial interactions with living systems will enable us to design new nano-based therapies and diagnostic platforms, as well as ensuring that nanomaterials not intended for human contact can be utilized safely. By combining physical chemical approaches with state of the art biological technologies we are framing and developing quantitative bionanoscience. On-going projects include the development of a kinetic model of nanoparticle uptake by cells; elucidation of the portals and mechanisms of nanoparticle uptake by various cells; development of a human blood-brain barrier co-culture model; and mapping of the spatiotemporal pathways utilised by nanoparticles in cells. Protein-Nanoparticle Interactions: Living systems never contact bare nanoparticle surfaces - rather they are coated by a dynamic and evolving layer of proteins, lipids and other biomolecules immediately upon contact with living systems. Much of our current work is directed to understanding the details of these evolving biomolecule coronas - identifying the proteins involved and how these evolve as the nanoparticles are trafficked in cells; connecting this to potential functional impacts in terms of changes in the protein conformation and protein mis-folding events; development of new approaches to map the outer layers of the biomolecule corona which interact with the cellular machinery; and understanding the rules governing nanoparticle-protein interaction. Quantitative BioNanoInteraction: We seek to catalyse the emergence of a new quantitative approach to understanding how nanoscale objects interact with living matter. Thus, we develop novel labelled nanoparticle apply imaging and related techniques to follow them entering and moving within cells. These measurements we seek to make reproducible and quantitative and this leads us to push typical methods of cell culture, cell biology, nanoparticle dispersion technology, and related elements to a level far beyond the usual requirement. In particular, we can now reproducibly follow several classes of nanoparticles into cells lines, with reproducibility and precision more familiar in physical sciences. Systems Approaches: Here we apply the methods of simulation, modelling, theory and mathematical approaches to understand issues of dynamical arrest, correlations between events, and to develop a quantitative understanding of nanoparticle impacts on living systems. Projects include the development of a framework for the understanding relationship between gene expression profiles and cancer onset; understanding slowed dynamics and more recently its application to intracellular processing and trafficking intermittency events, which are likely to have a very significant impact for biological systems. New Responsive and Smart Delivery Nanoparticles: Polymeric nanoparticles that can be loaded with therapeutic agents and tailored to adsorb specific proteins and thereby to target specific cellular trafficking pathways and reach specific sub-cellular locations is the dream of nanomedicine. In this arena, we are working on the development of such particles, tailoring the particle size, surface hydrophobicity, surface charge, surface ligands, and loading strategies to design smart delivery systems that can go with very high selectivity to target organs/tissues / sub-cellular organelles.