Imaging dynamics in biophysical/biochemical processes across the hierarchical scales (BioPro Network)

点击翻译按钮获取中文摘要

Biological tissues and organs undergo a constant state of dynamical structural and chemical changes with time, which can range from our joint tissues elastic recoil during walking to the slow tissue breakdown as we age, to the very rapid secretion and reaction of proteins by cells in response to sensed mechanical forces. Biological tissues are hierarchical in both structure and function, with protein and DNA architecture at the nano scale leading up to cells and fibrous extracellular matrices at the micron scale to organs at the largest scale. The way such organs operate in a dynamic environment cannot be inferred solely from the gene, but must take into account the processes happening at multiple levels. A classic example is how our joints deteriorate with age, which is - at the molecular level - governed by how proteins levels and composition, at one level higher how they aggregate differently into fibres with poorer elasticity, at a level higher still (microscopic) in how cells react to external loads by changing what proteins they secrete, and finally at the level of the whole organ in how the cell/tissue array becomes less resilient and breaks down with time. A grand challenge is to understand both what this hierarchy of dynamical processes are as well as how they affect tissue functioning, growth and disease. Currently, however, physical-science and engineering methods used in the biomedical field lack the capacity to image these processes dynamically, in a condition close to the living tissue and at multiple levels simultaneously. However, this is potentially possible, due to recent advances in physical-science based high energy imaging methods at central research facilities (like synchrotrons) in specialist methods like 3D X-ray imaging, microfocus diffraction, laser-scanning methods and the use of free-electron lasers to watch molecules vibrate at speeds many orders of magnitude faster than was previously possible. The challenge is coupling these with physiologically realistic environments to enable the imaging of dynamics of biophysical/chemical processes, bridging the huge temporal and spatial scales of these processes, and finally translating these technologies first to the laboratory and then into the clinic. In this network, we will work to make this potential a reality by bringing together leading physical-science and engineering researchers in the UK with biomedical researchers to attack the engineering and biological challenges in a team-effort. We will focus on three areas: i) developing experimental setups using these high energy methods which keep the tissue/cell/organ in a native state ii) devising methods to cross-correlate the information across techniques and iii) linking information obtained at different length scales into a unified picture. Our projects will focus on musculoskeletal degeneration at multiple scales, but we will seek to develop methods that are as widely applicable to other conditions as possible.We will run several short-term proof of concept projects which will allow these teams to test new ideas and whether they work, and fund researchers to spend short-term visits in each other's labs which will help transfer from the physical to the biological sciences. If these results show promise, they will lead to full-scale projects where a biomedically or clinically relevant application can be developed in full. We will hold a range of activities to explore and identify challenges (sandpits and workshops) and to present and analyse the results (annual conferences). The methods and tools we develop will be made widely available to the general academic community to bring them sooner to benefit the general public. Our network, in short, will provide the key proving-ground where the most advanced high energy techniques to analyse complex matter, available only at central facilities, are adapted and made applicable to solve critical questions in the life- and medical-sciences.