Research Interests

His prime research interest is how the information encoded in chromosomes instructs building of the most complex organ, the brain, and allows an organism to perform elaborate tasks.

Research description

Alternative mRNA processing in neurons

Post-transcriptional control of gene expression in neuronal development and function.

Post-transcriptional regulation of gene expression is a major mechanism to generate organismal complexity from a limited number of genes. Particularly impressing is the large number of genes that are alternatively spliced; and this type of gene regulation is most prevalently found in the brain. Miss-regulation of pre-mRNA processing, including alternative splicing, as a result of genetic polymorphisms or of toxicity from small molecules, results in numerous brain diseases and neurological disorders. Our laboratory investigates mechanisms of alternative pre-mRNA processing in neurons. In particular, we examine how RNA binding proteins decode the degenerate sequence information present in short and spaced regulatory elements of pre-mRNA to generate high fidelity in gene-specific regulation.

We are using the sophisticated genetic tools of the fruit fly Drosophila in combination with chemical genetics to study alternative pre-mRNA processing. One of our favourite molecules is the neuronal splicing regulator ELAV. ELAV is the founding member of a family of RNA binding proteins and is a homologue of human Hu proteins. The activity of ELAV/Hu family proteins is tightly regulated and aberrant regulation results in neurological phenotypes. We aim to understand the mechanisms used by ELAV/Hu family proteins to generate gene-specificity in alternative pre-mRNA processing and how the activity of ELAVHu family proteins is regulated by cellular signalling. At the organismal level, we are studying the cellular mechanisms regulated by ELAV/Hu family proteins and how ELAV/Hu family proteins impact on neuronal development and function in health and disease.

Scientific Inspiration

Seymour Benzer: He formulated the idea that genes direct behaviour making him the founder of Neurogenetics. He identified the first gene involved in learning & memory. Earlier, he had identified the genetic code by saturation mutagenesis of a phage.

Michael Rosbash: I know Michael from many discussions during my post-doc time in Brandeis as an excellent scientist. He has a very impressive publication record and for his seminal work on biological clocks in Drosophila, he was awarded the Nobel Prize in 2017.