From flies to fish to therapy
Van Leeuwenhoek Lecture on BioScience.
Philip Ingham is Inaugural Director of the Living Systems Institute at the University of Exeter, UK. Previously he was Toh kian Chui Distinguished Professor and Vice Dean for Research at the Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore and prior to that was Deputy Director of the A*STAR Institute of Molecular and Cell Biology also in Singapore. A graduate of Cambridge University, he has used genetic approaches to analyse developmental processes both in Drosophila and zebrafish for nearly 40 years. He is an elected member of the European Molecular Biology Organisation (EMBO) and Fellow of both the UK Academy of Medical Sciences and the Royal Society. He was awarded the Medal of the Genetics Society of Great Britain in 2005 and the Waddinton Medal of the British Society for developmental Biology in 2014.
In 1980, Nüsslein-Volhard and Wieschaus published the first report of their ground-breaking saturation mutagenesis screen in the fruit-fly Drosophila. In it, they described the isolation of mutations affecting the segmental organization of the embryo, findings that set the foundation for a revolution in our understanding of the genetic basis of animal development. Molecular cloning of these genes and the development of techniques for visualizing their expression in the embryo played a key part in revealing the molecular basis of embryonic patterning. Combined with genetic epistasis analysis, these techniques facilitated the elucidation of signal transduction pathways that mediate intercellular interactions within each body segment.One of these signaling pathways transduces the activity of a previously uncharacterized signaling protein encoded by the segment polariy gene, Hedgehog. Molecular screens for vertebrate homologues of this gene revealed a small family of proteins that were subsequently shown to play fundamental roles in the development of all vertebrates, including humans. Moreover, dysregulation of the hedgehog signaling pathway was found to underlie the ontogeny of a number of cancers, including Basal Cell Carcinoma (BCC), the most common canncer amongst Caucasians. Screens for antagonists of the Hedgehog pathway led to the development of a novel drug, vismodegib, which in 2012 gained FDA approval for use in the treatment of metastacic BCC. This successful exploitation of knowledge of Hedgehog signaling derived from studies in Drosophila, provides an important illustration of how basic curiosity-led research can inform the development of precision medicine.
May 18, Andy Knoll (Harvard)
June 29, Alain Arneodo (Bordeaux)