Biochemistry: Now Live and in Color
Scientists at the Interfaculty Institute of Biochemistry (IFIB) develop a method to visualize cell signalling in real time in living mice.
Scientists at the Interfaculty Institute of Biochemistry (IFIB) in Tübingen have collaborated with colleagues in Bochum, Boston, and Lübeck to visualize biochemistry in live mammalian organisms. The cyclic nucleotide cGMP is an important second messenger in the cardiovascular and nervous system. It relays signals from natriuretic peptides as well as NO and other gasotransmitters. Drugs that increase the intracellular cGMP concentration are used in the clinics, for instance, organic nitrates for the treatment of angina pectoris or sildenafil (Viagra®) for erectile dysfunction and pulmonary hypertension. Recent results suggest that the physiological outcome of cGMP signal transduction depends on the spatiotemporal profiles of the intracellular cGMP signals and the prevalence of global versus local cGMP pools. To improve our understanding of cGMP’s mechanisms of action, (patho-)physiological functions, and therapeutic potential, it is highly desirable to monitor its spatiotemporal dynamics in native systems such as living cells, tissues, and organisms.
In the new study, transgenic mouse lines were generated expressing a cGMP indicator protein that changes its fluorescence upon binding of cGMP, so that cGMP can be monitored and quantified in real time in live cells (see upper part of the figure). Proof-of-principle experiments showed that cGMP can indeed be visualized in primary cells and tissues isolated from these mice and, importantly, also in the vasculature of live animals (see lower part of the figure). This is the first time that intracellular signalling via cGMP has been observed under native conditions in vivo in a mammalian organism. It is anticipated that the cGMP sensor mice will become useful tools not only for basic cGMP research and companies working on cGMP-modulating drugs; they should also contribute to a better understanding of biological information processing in health and disease in general.
The study was published in Circulation Research:
Thunemann M*, Wen L*, Hillenbrand M, Vachaviolos A, Feil S, Ott T, Han X, Fukumura D, Jain RK, Russwurm M, de Wit C, Feil R. Transgenic mice for cGMP imaging. Circ Res. 2013; first published on June 25. [DOI]
The Feil group is located at the IFIB and a member of the newly established DFG Research Unit “cGMP Signalling in Cell Growth and Survival“ (FOR 2060):
Prof. Dr. Robert Feil
Interfakultäres Institut für Biochemie
Tel +49-7071-29 73 350