Bringing Order to the Chaos of Being - How Genes Control Development

Biologist Ingrid Lohmann investigates the mechanisms that let a single fertilised egg develop into a complex organism. In her research, the scientist relies on the help of a small fly: Drosophila melanogaster a star among laboratory animals.

Ingrid Lohmann has worked her way up step by step: from the slime mould Dictyostelium to the fresh water polyp Hydra, a simple multi-cellular organism, and finally Drosophila melanogaster, the “dark-bellied dew lover”. For decades, the tiny but complex fly with the poetic name has helped biologists bring order to the chaos of being and understand the basic principles of life. Ingrid Lohmann became familiar with the famous insect when she began working in the laboratory of renowned molecular biologist William McGinnis at the University of California in San Diego after earning her PhD. “That was a revelation for me”, she remembers. “With Drosophila”, the biologist learned, “almost anything is possible.”

Dr. Ingrid Lohmann

And indeed, most of what science knows today about genes and heredity was discovered in research on Drosophila, a star among lab animals. Ever since, Ingrid Lohmann has remained true to the minute, double- winged creature that has much more in common with us than it lets on at first glance. With the help of Drosophila, and supported by the research structures of the “Cellular Networks” cluster of Heidelberg University, Lohmann wants to help solve one of the most important questions of biology: how does an organism develop from a single fertilised egg?

The scientist is especially interested in a family of developmental genes called “Hox”. The products of Hox genes act as “transcription factors” in the cell: they control the activity of a multitude of genes that are responsible for the early development of an individual. Most importantly, Hox genes ensure that the body of the embryo develops different sections along its longitudinal axis, such as the head and torso, and that it forms the associated extremities.

The astonishing thing is that Hox genes fulfil this task in all animals that have a longitudinal axis: in the fresh water polyp Hydra just as in the insect Drosophila or in vertebrates like humans. “Hox genes are master regula- tors of development”, says Ingrid Lohmann. That doesn't just apply to the development of individual species, but to all of evolution, during which the Hox genes remained virtually unchanged in different phyla and orders. That is why the genes that form a human's body are nearly identical to the ones that contain the blueprint for the fly.

During her research in San Diego, Ingrid Lohmann found an important mechanism that Hox genes use to unfold their creative power: they contribute to the regulation of programmed cell death (apoptosis) and target certain cells for destruction during development. This mechanism is essential to shape organs in all animals and humans, and is, for example, responsible for transforming a shapeless paddle-like tissue into the five fingers of a hand.

In 2010 Ingrid Lohmann became head of a research group in the “Cellular Networks” Cluster of Excellence. In order to take this job, she moved to Heidelberg with her husband Jan Lohmann and their two sons. Jan Lohmann, also a member of the cluster, heads a new division for stem cell biology at the University's Centre for Organismal Studies. “We're a package deal”, says Ingrid Lohmann and smiles. “With the Cellular Networks cluster, Heidelberg University not only offered us optimal possibilities for interdisciplinary research, but also the best possible conditions for combining a family with a career.” Right now, Ingrid Lohmann is investigating the way in which Hox genes connect nerve cells to form circuits in the brain and stimulate complex behaviour - such as the crawling of Drosophila larvae towards food or the chewing movements of jaw muscles. The biologist and her ten colleagues are also interested in the significance of the Hox genes for the preservation and differentiation of stem cells, the all-rounders among cells. And in the question of how mutations in Hox genes can contribute to cancer formation. Drosophila may still be an untried test subject in this particular area, but Ingrid Lohmann is turning the insect into the “model organism” for cancers, in cooperation with scientists of the German Cancer Research Center that is just around the corner from her lab. In the scientist's opinion, that is the decisive “Heidelberg advantage” and the distinguishing characteristic of the Cellular Networks cluster: the immediate access to state-ofthe- art technology, e.g. powerful microscopy equipment, the possibility of quickly involving researchers of other disciplines in her own research, and the exchange of ideas in informal talks with excellent scientists - “right outside in the hall or in the stairway, if need be.”