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Professor Philip W. Ingham FRS

After graduating in Genetics from Cambridge University in 1977, I did research for my D.Phil (PhD) in Developmental Genetics at Sussex University followed by postdoctoral work in Strasbourg, France and the ICRF in Mill Hill, London. In 1986, I took a Research Scientist position at the MRC LMB, Cambridge before moving to a similar appointment at the ICRF Developmental Biology Unit in Oxford. I became a Principal Scientist at the ICRF in 1994, relocating my group to the Lincoln's Inn Fields laboratories in London. In 1996, I was appointed Professor of Developmental Genetics at the University of Sheffield and subsequently became Director of the MRC Centre. Since 2006 I have been on part-time secondment to the Institute of Molecular and Cell Biology in Singapore where I am Deputy Director.

Research

Summary for nonspecialist

The transmission of signals between cells is a key process, both during the development of an organism and throughout its subsequent life. Such cell-cell signalling controls, for instance, the formation of specific nerve cells and muscles in the developing embryo as well as the maintenance of stem cells that continually replenish our skin or the linings of our gut. Not surprisingly, the break down of such signalling can have disasterous effects, causing both birth defects in the newborn child as well as cancers during later life. To understand how these signalling processes work, we study the genes that control them in organisms such as the fruitfly or the tropical zebrafish.

We study these organisms because they are easy to maintain in the laboratory, their embryos are readily obtained without any surgical intervention and their genomes show remarkable levels of similarity to our own. The knowledge generated by our studies should help in the design of drugs to modulate signalling pathways in cancerous cells as well as the manipulation of the differentiation of stem cells for therapeutic use.

Fibres and dystrophin localized to the vertical myosepta in a wild type embryo.

Technical Summary

A long standing interest of my research group has been the role of secreted signaling molecules in pattern formation and organogenesis. We have focused in particular on the Hedgehog (Hh) protein family, using genetic analysis in Drosophila to elucidate the pathway by which these proteins signal to the nucleus and using the zebrafish as a model in which to study their roles in vertebrate development.

One process that we have studied in some detail is the allocation of cells to distinct myogenic fates. We have found that Hh signaling plays a key role in specifying muscle fibre type and have identified the transcription factor Prdm1 as a critical target of Hh signaling in this cell fate decision. Using Chromatin immune precipitation combined with microarray analysis (ChIP on chip) we have identified multiple targets of Prdm1 in myoblasts.

A second area of investigation is the mechanisms by which Hh pathway components function.  The unique properties of the zebrafish embryo make it very well suited to the in vivo analysis of signaling processes at the cellular and sub-cellular. We are particularly interested in the trafficking of the transmembrane proteins Patched and Smoothened and the nuclear cytoplasmic shuttling of the Gli transcription factors.

We are also interested in the use of the zebrafish as a system in which to model human disease related processes. We have collaborated with clinician scientists in the establishment of models of Parkinson's disease, the inflammatory response and arteriogenesis and are exploring the use of these and other models as the basis for chemical genetic screens.

Markers of distinction:

• Balfour Memorial Prize (Genetical Society of Great Britain), 1990
• Medal of the Genetics Society of Great Britain, 2005
• International Scientific Advisory Board Member:
• Max Planck Institute for Developmental Biology (Tübingen)
• The Sars International Centre for Marine Biology (Bergen),
• The Karolinska Institute Centre of Excellence in Developmental Biology (Stockholm)
• The Wellcome Trust Sanger Institute (Hinxton)
• Editorial Advisor Board member:
• Developmental Cell, Current Biology, EMBO Journal, Current Topics in Developmental Biology, Mechanisms of Development, Genome Biology, EMBO Reports, Developmental Biology, Head of Faculty, Faculty of 1000
• Member of European Molecular Biology Organisation (EMBO) (1995)
• Fellow of the Institute of Biology (2000),
• Fellow of the Academy of Medical Science (2001),
• Fellow of the Royal Society (2002)
• Honorary Fellow of the Royal College of Physicians (2007)

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