LNB research topics and support activities
To comprehend how matter creates life requires visualising the living cell in atomic detail. To this aim, we develop novel technologies that are based on electron diffraction of frozen, hydrated biological samples. We have demonstrated (using biological and organic nano-crystals) that electron diffraction data can in principle unlock high-resolution information way beyond what conventional electron microscopy can deliver, and that this also applies to other biological samples. To exploit this novel approach in the study of cellular processes, we scan samples with a coherent beam with a diameter down to several nanometers, and measure the diffracted electrons using modern hybrid pixel detectors as developed by PSI’s detector group. For phasing of these data, we develop a range of methods that combine experimental and computational approaches. We apply our research to the study of the molecular response to mitochondrial stress central to neuro-degeneration and aging.
Jan Pieter Abrahams, Group leader
Physics of electron diffraction by living matter; mitochondrial stress
Tatiana Latychevskaia, Scientist
Decoding electron diffraction data
Eric van Genderen, Scientist
Optimal electron diffraction of living matter
Cellular Structure Imaging
Our focus is electron and X-ray imaging and related methodological development. Takashi Ishikawa is interested in eukaryotic cilia/flagella, which are microtubule-based organelles and enable cellular motility, extracellular flow as well as sensing. His group pursues 3D imaging of motor, regulatory, and cytoskeletal proteins, intact cilia and ciliated cells and tissues, employing single particle cryo-EM, cryo-electron tomography and ptychographic X-ray tomography. Their aim is to reveal molecular mechanism of ciliary function. The Benoit group is interested in molecular and cellular structures of membrane proteins, especially receptors. They use single particle cryo-EM to analyze molecular structure of membrane proteins, developing related genetic engineering techniques. The main target of the Shahmoradian group is cryo-EM and ptychographic X-ray tomography of neural cells and brain tissue. Their main interest is the Lewy body, which is a key to understand Perkinson’s disease.
Takashi Ishikawa, Group leader
Cellular and molecular structural biology on eukaryotic cilia and flagella
Roger Benoit, Scientist
Engineered scaffolds for protein structure elucidation by cryo-EM and crystallography
Structural Biology of Neuronal Systems
An important scientific aim of the molecular neurobiology group is to expand fundamental molecular studies on isolated, purified proteins that are associated with neuronal functioning and neuronal stress, to include the impact at high resolution of physiological factors and eventually a cellular context. Thus, we anticipate contributing to deeper understanding of the fundamental, molecular causes of a range of devastating neuronal diseases associated with aging. Signalling and other membrane mediated responses are core aspects of such causes.
Jan Pieter Abrahams (ad interim), Group leader
Jinghui Luo, Scientist
Structure and function characterization of neurodegenerative amyloid proteins by integrative biophysical methods
The mechano-genomics group is focused on understanding the mesoscale functional links between cell mechanics, genome organization and gene expression during cellular ageing, rejuvenation and tissue homeostasis. Towards this, they use state-of-the art single-cell correlative imaging, micro-fabricated biointerfaces, functional genomics and machine learning methods. These studies, aimed at an in-depth understanding of the mechanical regulation of genome programs have major implications in regenerative medicine and early cancer diagnostics. On the computational side, the group collaborates closely with Caroline Uhler’s group at MIT.
For more information see the website of the Mechano-Genomics Group.