Through her project “Transcriptional priming in neuronal diversification”, IMP group leader Luisa Cochella aims to understand the gene regulatory principles underlying the specification of cell types in an animal during embryonic development. In order to generate the many different cell types that form an animal from a single genome, each cell has to express a distinct set of genes, encoding specific structural and functional components that make each cell type unique. The expression of these gene sets is controlled by transcription factors that typically act in a combinatorial way, with two or more factors acting together to activate expression of a gene. The combinatorial activity of transcription factors enables the production of a large cellular diversity.
Cochella and colleagues had previously described a novel mode of combinatorial activity of transcription factors, in which two transcription factors act on a gene at different time-points during the development of a cell. The first transcription factor “primes” the gene and the second can then “boost” its expression a few cell divisions later. This mechanism enables a new dimension in which transcription factor activity can be combined to increase cellular diversity. One example is the generation of morphologically symmetric pairs of neurons with asymmetric properties in the brain of the nematode worm C. elegans. But this mechanism likely acts in multiple developmental contexts, for example in the vertebrate retina in which different progenitor cells are primed early in development, biasing them towards the production of different types of retinal cells.
The project of Luisa Cochella aims to illuminate our understanding of the mechanism and impact of transcriptional priming on the generation of neuronal diversity during development. Cochella and her Team will address this using C. elegans, a unique experimental system with a well-defined nervous system and a fully mapped developmental cell lineage. Apart from generating valuable knowledge for future research, the results will also be important for current efforts to directly generate different cell types in vitro.
The project of Lukas Landler, a postdoctoral researcher in the lab of David Keays, seeks to elucidate the neuronal basis of magnetoreception. Many species on the planet rely on the Earth’s magnetic field for navigation. Loggerhead sea turtle hatchlings, for instance, use magnetic field information on their impressive migration from the coast of Florida along the Atlantic gyre towards the North-African coast and back again. That animals can detect magnetic fields has been established without doubt. However, we still do not understand how they do this or where the receptor cells are located. A number of ideas have been proposed that are based on either the presence of an intracellular compass, a mechanism that relies on light, or the direct conversion of magnetic information into electrical signals. Research progress has been slow because most commonly used magneto-sensory animals are protected, migrate over large distances, or cannot be studied in the lab.
Landler plans to explore the biology underlying the magnetic sense, employing mice as a model system. He will study how magnetic stimuli influence neuronal activity in the brain, thus guiding the search for the primary sensory cells. In his experiments, he will exploit the latest advances in light sheet microscopy and the broad array of genetic tools available in the mouse. The project should not only provide a foundation to clarify how animals detect magnetic fields, it is also likely to spur innovation in other fields of science. Understanding how a radical pair based magnetic compass functions may assist in the developing of quantum computing at room temperature and inspire the designs of very small magnetic detection devices.