Theory predicts that with an ultra-short and very bright coherent X-ray pulse, a single diffraction pattern may be recorded from a large macromolecule, a virus, or a cell before the sample explodes and turns into a plasma. The over-sampled diffraction pattern permits phase retrieval and hence structure determination. The first free-electron lasers (FELs) capable to deliver ultra bright and very short X-ray pulses for such experiments have recently started operations. These are the most brilliant sources of X-rays to date, exceeding the peak brilliance of conventional synchrotrons by a factor of 10 billion. In the duration of a single flash, the beam focused to a micron-sized spot has the same power density as all the sunlight hitting the Earth, focused to a millimetre square. The interaction of an intense X-ray pulse with matter is profoundly different from that of an optical pulse. A necessary goal of the programme is to explore photon-material interactions in strong X-ray fields. Our aim in structural biology is to step beyond conventional damage limits and develop the science and technology required to enable high-resolution studies of single biological objects near the physical limits of imaging. Eligible targets include single virus particles, organelles, cells, nanocrystals, and isolated macromolecules. A particular aim of the planned work is to obtain high-resolution structures for giant viruses. The challenges engage an interdisciplinary approach, drawing upon structural sciences, biology, atomic and plasma physics, optics and mathematics. The potential for breakthrough science is great with impact not only in biology or physics but wherever dynamic structural information with high spatial and temporal resolution is valuable. The overall relevance of the programme extends beyond basic science, to technologies of essential importance to a future Europe.