Research themes
Core research themes
Using light as a tool for life sciences research provides a non-invasive, ultra-fast and very precise method to visualize, diagnose, sense, target and manipulate biological specimens, from single proteins or nucleic acids to entire cells and organisms. The research program at CoB aims at an integrated understanding of biological function at the nanoscale both in vitro and in the complex in vivo environment of cells and model organisms. By merging super-resolution 3D imaging, manipulation, computational modelling and ultra-sensitive sensing approaches, we aim to have an impact in fundamental understanding of life, how disease emerges and provide solutions for its diagnosis and treatment. The CoB is structured around three main Core Research Themes: 3D imaging across scales, forces in biology and neurophotonics.
Imaging across scales
Improving 3D imaging inside cells or living organisms requires input from multiple disciplines: (engineering) laser sources with tailored beam shapes, (physics) improved optics such as a adaptive optics and light-sheet strategies to deliver light in more efficient and selective ways, (modelling) intelligent data analysis algorithms to enhance the data content (mathematics) and (chemistry) new labels and tagging methods.
Current imaging techniques allow spatial resolutions well beyond the diffraction limit and penetration depths unthinkable just a few years ago, but they are still limited, particularly when the targets are thick specimens with heterogeneous refractive index profiles. At the CoB, we are exploring routes to better techniques, including the use of structured beams in light-sheet microscopy, the use of multi-photon methods to increase penetration depth and axial resolution. A significant effort is directed to integrate methods in ‘hybrid microscopes’ that can extract multiple parameters at complementary temporal and spatial scales.
Forces in biology
Forces and mechanical properties influence biological function from molecules to genes to cells and tissues. Force detection and sensing are processes shared by all living organisms and some human diseases are related to changes in mechanical properties. However, the mechanisms underlying the generation of forces, their duration and magnitude and how they propagate are not well understood. (Image: UM-SCC1 cancer cells, courtesy of Marcel Schubert and Eleni Dalaka). Our aim is to develop new optical technologies that can induce and/or sense forces at molecular and cellular level and between neighbouring cells and their environment. Additionally, we wish to combine these ‘force imaging’ technologies with complementary optical imaging methods to extract an integrated vision of the range of forces experienced and exerted by molecular machines and cells, how these forces are transduced in a cellular environment and how mechanical processes are temporally and spatially compartmentalized.
Neurophotonics
There is no doubt the brain is the most complex organism and understanding how it functions constitutes one the most challenging tasks facing life sciences research in the 21st century. There is not only a need for innovative techniques capable of imaging, but also for methods combining structural data at the nanoscale with functional recording of neuron activity. (Image: cultured neurons expressing Cheriff-eGFP (white) and jRCaMP1 (red), courtesy of Marcel Schubert and Andrew Morton). By targeting the molecular pathways that enable neuron function, synaptic communication and dysfunction and how signals are transmitted within network architectures we aim to understand how organisms and animal models produce behaviour. We expect this knowledge to contribute to understanding the molecular and cellular-level basis of neurological disorders including Alzheimer’s, Huntington’s, Parkinson’s, autism and Motor Neuron Disease (MND), Amyotrophic Lateral Sclerosis (ALS), Spinal Muscular Atrophy and learning disorders such as dyslexia.
