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All a question of visibility

München, 08/08/2016

Molecular breadboards
DNA origami provides a method for building nanostructures that can serve as docking stations – rather like the holes in an electronics breadboard – for molecules such as fluorescent agents that be visualized by microscopy. Jungmann is now focusing on the development of new fluorescent tags, whose emission characteristics can be tightly controlled and differentiated – all in the service of increasing optical resolution. “The decision to come back to Munich and specifically to LMU was an easy one,” he says. “Universities and Max Planck Institutes (MPIs) offer ideal conditions for research.” His CV reads like a model of careful planning, and it tells a success story. He is co-founder of a company in the US, and holds a dozen patents – an impressive record for a 35-year-old. “It looks like plain sailing in retrospect, but in fact much depended on incidental encounters and decisions based on instinct.” But then, following one’s instincts in choosing labs where one can learn something new, and recognizing trends that promise to become “rocket science” or simply offer a stimulating environment for teamwork is itself a kind of plan.

Jungmann currently heads an Emmy Noether Junior Research Group in the Faculty of Physics at LMU, and the MPI for Biochemistry in Martinsried. He recently won one of the highly endowed Starting Grants awarded by the ERC, and a grant of a million euros from the Max Planck Foundation. A visit to his lab at the MPI suggests that this money is being well spent. Here one finds the light microscope with the highest resolution – 5 nm – currently attainable anywhere in the world. It is basically a classical fluorescence microscope, but with innovative modifications designed and built by Jungmann’s group. Laser, mirrors, objectives and cameras come from commercial sources, but his coworkers are responsible for the overall conception of the instrument. This is one reason why interdisciplinary collaboration in well integrated teams is so important. “We can move faster because communication is simpler and coordination easier – and we make fewer mistakes because we have experts for all the details,” Jungmann explains. Factors such as these help to explain how one can make such rapid progress: Ideas are freely exchanged and can be speedily assessed and implemented. Jungmann belongs to a new generation of researchers in Germany who have learned to work as members of networks. These transparent and cooperative structures have replaced the hierarchically organized and inward-looking systems of yesteryear.

Jungmann learned how productive this approach can be when he joined the laboratory led by William Shih and Peng Yin at the Wyss Institute for Biologically Inspired Engineering at Harvard Medical School in Boston. The Institute employs specialists in all relevant disciplines, from mechanical engineers to biologists and computer scientists. And this is the model he himself sets for his doctoral and Master’s students. For example, he spent 30,000 euros on a simpler version of his record-breaking microscope solely for their use – designed by one of his PhD students. “It gets down to 20 nm,” he says. “Not bad for a do-it-yourself job.”

After going through the Harvard mill
Three of his doctoral students did their Master’s under his supervision when he was still at Harvard. That extends their network of international contacts, “and having successfully gone through the Harvard mill is a recommendation in itself,” he adds. These graduate students now form the experienced core of his team, something even the best group-leader can’t do without. It also means that ideas for projects are never in short supply. Jungmann has high hopes for his DNA barcodes, which can be targeted to a plethora of specific proteins and RNA sequences, serving as unambiguous markers for each. These markers are equipped with photoswitchable dyes which, depending on their precise structure, blink on and off for shorter or longer periods, and with tunable intensities. “Our method is simpler than all other modes of super-resolution microscopy,” Jungmann asserts – and he is thinking here not only of imaging individual cells but also cell collectives in tissues. In fact, it is possible to observe and analyze hundreds of cells at a time using short, dye-labeled DNA strands as highly specific beacons.

The funds made available by the Emmy Noether Program and the ERC Starting Grant, together worth some 3.5 million euros, provide him with the scope to pursue his dream for the next several years. In addition, LMU now offers ERC Starting Grantees tenure-track professorships (W2) and Jungmann is among the first to profit from the scheme. On August 1st he became Professor for Molecular Imaging and Bionanotechnology. “That gives me a degree of security, though it does not guarantee that I will later obtain an academic chair,” he says. His work will be reviewed in 5 years’ time. “And that is of course a further incentive for me,” he adds – with a grin.
Hubert Filser

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