RNA biology, metabolism and molecular medicine
The Hentze group combines biochemical and systems level approaches to investigate the connections between gene expression and cell metabolism, and their role in human disease.
Previous and current research
Important steps in the control of gene expression are executed in the cytoplasm by regulation of mRNAs via RNA-binding proteins (RBPs) and non-coding regulatory RNAs (e.g. miRNAs). We are elucidating these regulatory mechanisms, combining ‘reductionist’ biochemical and systems level approaches in mammalian, yeast and Drosophila model systems.
We recently developed ‘mRNA interactome capture’ to define ‘all’ RBPs associated with mRNAs in vivo (Castello et al., 2012). This work offers an ideal starting point for exploration of ‘REM networks’ (Hentze & Preiss, 2010), which we expect to connect cell metabolism and gene expression in previously unrecognised ways (figure 1).
Within the Molecular Medicine Partnership Unit (MMPU), we are investigating the post-transcriptional processes of nonsense-mediated decay (NMD) and 3’ end processing and their importance in genetic diseases (with Andreas Kulozik, University of Heidelberg).
Our second major interest is the biology of mammalian iron metabolism (figure 2). This work includes the definition of the functions of the IRE/IRP regulatory network and its crosstalk with the iron hormone hepcidin. Within the MMPU (together with Martina Muckenthaler, Heidelberg University), we study the molecular basis of genetic and nongenetic diseases of human iron metabolism. Our work employs conditional knockout mouse strains for IRP1 and IRP2 and mouse models of iron metabolism diseases.
Future projects and goals
- To uncover the basic mechanisms underlying protein synthesis and its regulation by miRNAs and RNA-binding proteins in cell metabolism, differentiation, and development.
- To explore, define, and understand REM networks.
- To help elucidate the role of RNA metabolism in disease, and to develop novel diagnostic and therapeutic strategies based on this knowledge.
- To understand the molecular mechanisms and regulatory circuits underlying physiological iron homeostasis.
- To contribute to the elucidation of the molecular pathophysiology of common iron overload (haemochromatosis), iron deficiency (anaemia) and iron management (anaemia, Parkinson’s disease) disorders.