Philipp keller was selected as the 2017 John Kendrew Young Scientist Award winner for ground-breaking work on light-sheet microscopy and computational technologies that allow whole-animal imaging. Much of the image analysis software and microscope blueprints developed by Philipp and his team are now in the public domain, and the work has granted him an outstanding record of publications in high-ranking journals (40 in the last seven years). Philipp, now Group Leader at the Janelia Research Campus of the Howard Hughes Medical Institute, studies early brain development and function. He has co-organised several conference series that have strengthened bonds between EMBL and Janelia Research Campus, and participates in philanthropic activities for children’s science education.

Read interview with Philipp: Fish development unmasked

Philipp Keller’s fascination with animal development dates back to his training as a physicist. “I enjoy understanding how complex systems work,” he says. “Some of the most complex things, you will find in biology – like a developing embryo or a higher functioning brain.” After studying physics and computer science at the University of Heidelberg, he went on to complete his PhD at EMBL. Not only did he have the opportunity to combine physics and biology studies during his PhD, but he also was able to work in three different labs and with three different advisors – an interdisciplinary experience that helped direct and shape his research.

First Keller worked in Joachim Wittbrodt’s group on a project focused on visualising and reconstructing how a zebrafish forms from a single cell. They wanted to know how the single cell divides, migrates and develops into other tissues to form an embryo. It had never been seen before and it was technically difficult to study a vertebrate embryo at the cellular level. “It was a technology problem,” Keller explains, “so it was natural to form a collaboration with a group that was looking into new tools. I think EMBL is set up to encourage that.”

Keller then began work in Ernst Stelzer’s lab on a new kind of microscope, which he called the Digital Scanned Laser Light-Sheet Microscope (DSLM). While the group awaited some parts Keller needed in order to build the new microscope, Keller joined a third project headed by group leader Michael Knop: spore formation in yeast. “From a modelling perspective, it was interesting to me,” Keller says. “We wanted to understand this process through computer simulation in addition to experiments.”

“I could see the developing fish right in front of my eyes!”

Once the parts to create the DSLM in Stelzer’s lab arrived, Keller found that the skills he’d learned in computational modelling came full circle in the zebrafish project. The DSLM was faster and produced higher quality images than existing microscopes, which made it possible to image a developing zebrafish embryo for the first time.

“Rather than trying to work through a bunch of text and numbers, I could see the system – the developing fish – right in front of my eyes!”, Keller says. This gave him better insight into how biologists think about development at the cellular level.

After Keller completed his PhD at EMBL, he set off to map complex systems in the body as a group leader at the Janelia Research Campus of the Howard Hughes Medical Institute in Virginia, USA, where he is currently based. He continues to research developmental biology, in particular the nervous system and how it develops and first starts to function in the course of embryogenesis. “It’s not only important to know where the cells are located and what shape they have,” he says, “but it is also important to know what they can do – like how they become active, how they fire for the first time and how they interact with other cells to form complex circuits.” One example is looking at how activity of neurons in certain regions of the brain changes as we execute a certain behaviour, like walking or stopping.

But in order to see such minute and speedy activity, which can be measured by monitoring calcium concentrations in the neurons, his lab needs sensitive microscopes. Neurons are flooded with calcium when they fire, and they are emptied when they reset. It is possible to detect this activity with an indicator sensitive to calcium concentrations or even by measuring the electrical signals themselves, but neurons can spike one hundred or even one thousand times per second. “If you want to get the timing relationship right between cells, you need to match these timescales,” Keller explains. “This is why we want the microscopes to be as fast as possible, and this is why we are building a new generation of them.”

By Margaux Phares and Sarah B. Puschmann