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Séminaire - Harald JanovjakSynthetic Physiology: Optical control of cellular signals

Abstract :

The development and function of multicellular organisms relies on the ordered communication of cells that function in networks and circuits. Our understanding of cellular communication and its physiological consequences hinges on the ability to modulate specific signals while monitoring effects in intact tissues and behaving animals. In our laboratory, we combine synthetic biology and cell biology to modulate the communication between cells and ultimately intervene with physiology. To achieve this goal, we re-engineer molecular components of the mammalian cellular communication machinery, currently in particular those components that control cell survival, to be responsive to new synthetic stimuli. These stimuli are novel ligands or, more recently, light in optogenetics, which offers control in space and time. For instance, we have recently developed receptor tyrosine kinases, such as the receptors for neurotrophic factors or EGF, that are activated by blue or red light in the absence of ligand.


 We also have found ways to control the function of “orphan” genes and receptors using optogenetics. By encompassing the development of novel molecular tools and their application in animal models, we attempt to open new avenues in the study of how cellular communication orchestrates
physiology.

Selected publications

"Spatio‐temporally precise activation of engineered receptor tyrosine kinases by light" M. Grusch, K. Schelch, R. Riedler, E. Reichhart, C. Differ, W. Berger, A Ingles-Prieto & H. Janovjak EMBO Journal (2014) 33: 1713-1726.
 

 “Quantification of riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in mammalian model cells by CE with LED-induced fluorescence detection” J. Hühner, A. Ingles-Prieto, C. Neusüss, M. Lämmerhofer & H. Janovjak Electrophoresis (2015) 36: 518-525.


 "Optical control of ligand-gated ion channels" S. Szobota, C. McKenzie & H. Janovjak Ion Channels Methods and Protocols (2013) 998: 417-435.

Scientific focus :

We work at the interface of synthetic biology and mammalian physiology in the new research field synthetic physiology. The past decades have seen the emergence of synthetic biology, and with its paradigm ‘build to understand’, synthetic biology has proven to tackle the most complex biological problems. We are exploring synthetic principles for understanding and manipulating animal physiology. In past few years, our focus was on the ‘synthetic’ of synthetic physiology and we established new methods to control the signaling and behavior of nerve cells, cancer cells and key cell populations involved in metabolism.

Our methods offer spatial and temporal precision and included but were not limited to optogenetics. We are currently transitioning to the ‘physiology’ of synthetic physiology with a focus on understanding/manipulating cell signaling and behavior in tissues affected by disease. Our interdisciplinary research builds on the development of new molecular tools and their applications in animal models (mouse and Drosophila) of disease.