As indicated in the 'Topics Covered,' this educational talk will introduce fundamental principles and concepts of synthetic biology and the capabilities that arise from them for molecular imaging across different scales and organ systems - to complement the expert talks by Drs. Jerala and Witney on designer proteins and genetic circuits and translational gene reporter imaging, respectively.
We especially invite students and postdocs to join us in this educational session and the following interest group meeting so we can connect the next generation of multidisciplinary molecular imagers.
Reporter genes such as GFP are indispensable for biological research, and targeted modifications of this protein have famously lead to variants with all colors of the rainbow.
As our understanding of biomolecules and fundamental cellular processes grows, the capabilities of synthetic biology expand far beyond reporter genes. Bottom-up biological engineering can construct designer DNA, RNA, proteins, protein assemblies, cellular compartments, …, to control cellular machinery and, e.g., reprogram input/output behavior of cells or install new cellular and tissue functions.
In a positive feedback loop, new biosynthetic sensors will further increase the capabilities of molecular imaging to quantify cellular parameters and reverse-engineer cell and tissue functions. Furthermore, molecular imaging will be vital to spatiotemporally control molecular interventions that can be exerted by bioengineered actuators such as optogenetic tools.
Importantly, because of the enormous success of cellular therapies such as those based on CAR T-cells, there is a growing need to monitor - and in the future control - the function of genetically modified cells in the body of patients. These exciting biomedical advances call for the combined expertise and joint efforts of synthetic biologists and molecular imagers as we will outline in this educational session.
Kitada, T., DiAndreth, B., Teague, B., Weiss, R., 2018. Programming gene and engineered-cell therapies with synthetic biology. Science 359, eaad1067.
Huang, P.-S., Boyken, S.E., Baker, D., 2016. The coming of age of de novo protein design. Nature 537, 320–327. doi:10.1038/nature19946
Sigmund, F., Massner, C., Erdmann, P., Stelzl, A., Rolbieski, H., Fuchs, H., de Angelis, M.H., Desai, M., Bricault, S., Jasanoff, A., Ntziachristos, V., Plitzko, J., Westmeyer, G.G., 2017. Eukaryotically expressed encapsulins as orthogonal compartments for multiscale molecular imaging. bioRxiv. doi:10.1101/222083
Massner, C., Sigmund, F., Pettinger, S., Seeger, M., Hartmann, C., Ivleva N., Niessner, R., Fuchs H., Hrabé de Angelis, M., Stelzl, A., Koonakampully, N., Rolbieski, H., Wiedwald, U., Spasova, M., Wurst, W., Ntziachristos, V., Winklhofer, M., Westmeyer, G.G. Genetically controlled lysosomal entrapment of superparamagnetic ferritin for multimodal and multiscale imaging and actuation with low tissue attenuation. Advanced Functional Materials, in press
Westmeyer, G.G., Jasanoff, A., 2007. Genetically controlled MRI contrast mechanisms and their prospects in systems neuroscience research. Magnetic Resonance Imaging 25, 1004–1010. doi:10.1016/j.mri.2006.11.027
Funding by the ERC-SG ‘Magnetogenetics’, the DFG priority program SPP 1665, and the Bavarian Research Network for Molecular Biosystems is gratefully acknowledged.
Keywords: synthetic biology, protein engineering, biological engineering, designer proteins, de novo proteins, directed evolution, reporter genes, genetic circuits, molecular sensors, molecular actuators, optogenetics, magnetogenetics, bacterial imaging, whole-cell sensors, theranostics, T-cell Therapy, CAR T-cells, image guided therapies