Ladurner Group

Previous and current research

Chromatin packages our genome. Whenever cells change their genetic programme, such as during development or upon environmental changes, chromatin needs to be remodelled. Our team identifies, characterises and exploits novel molecular mechanisms that underlie the plasticity of chromatin structure.

We focus on the role of distinct post-translational modifications, cellular metabolites and signalling-activated enzymes in regulating the assembly and remodelling of histone proteins in the nucleosome, the fundamental repeating unit of chromatin structure. For example, we discovered the first example of a protein module capable of recognising a post-translational modification in a histone protein (the so-called bromodomain) and reported the first example of metabolite binding function in a histone and other nuclear proteins (the so-called macrodomain). By carrying out this research, we are uncovering the fundamental mechanisms that govern the function of our complex genome and its ability to adapt to new environments.

Our approach is defined by a multidisciplinary combination of genetics, genomics, biochemistry, cell biology, biophysics, structural biology (X-ray crystallography) and the use of selected model organisms. This allows us to answer fundamental biological questions in chromatin biology and to identify novel paradigms of molecular recognition and biological regulation in a comprehensive manner.

Our current research is focused on three complementary areas of chromatin plasticity.We are dissecting the structure and function of important chromatin remodelling enzymes using a combination of high-resolution X-ray crystallography, biochemistry, protein engineering and in vivo approaches. Secondly, we are studying the biological role and cell biology of ADP-ribosylation, a post-translational modification involved in regulating chromatin structure and transcription upon a variety of environmental stresses, where we have pioneered the discovery of the ADP-ribose-sensing macrodomain proteins. Last but not least, we complement our studies in yeast and mammalian cells by studying memory formation in the fruit fly. By applying knowledge from the field of transcription and epigenetics, we are now dissecting the role of chromatin dynamics in the formation, consolidation and maintenance of organismal memory.

Future projects and goals

• Structure and function of chromatin remodelling nanomachines: histone chaperones and signalling-activated enzymes;
• Molecular dissection of cellular ADP-ribosylation: metabolic control of gene activity associated with ADP-ribosyl-recognition;
• Transcriptional and epigenetic basis for organismal long-term memory: genomic tools for the systematic dissection of tissue-specific gene activity.