Research

Professor Christian Siebold

Crystal structure of Sonic hedgehog (SHH) bound to its receptor HIP (Bishop etal 2009).
Repulsive Guidance Molecule (RGM) acting as a staple for its receptor Neogenin (NEO1), a complex important for axon guidance and BMP signalling (Bell et al 2013).

Structural studies on Morphogen Signalling

A handful of secreted morphogen signalling molecules, acting in a spatial and gradient-dependent manner, orchestrate the development of multicellular organism. Morphogen dysfunction leads to a range of diseases and defects in adult stem cell populations. Their importance in human disease has become increasingly clear over the past decade: dysfunctions of the pathway are known to lead to severe developmental defects, neurodegenerative diseases and cancer.

Our group seeks to generate mechanistic insights relevant to disease and embryonic development focusing on two fundamental morphogen signalling systems: the Hedgehog (Hh) and the bone morphogenetic protein (BMP) pathways. Extracellular Hh and BMP signals are mediated by various cell surface receptor molecules. We aim to unravel the molecular mechanisms underlying Hh and BMP interactions with their binding partners to obtain a better understanding of morphogen gradient formation and signal transduction across the cell membrane.

To achieve this, we are using structural biology techniques such as X-ray crystallography to obtain molecular snapshots of Hh and BMP interactions with other proteins. We combine atomic details from in vitro structural and biophysical studies on single molecules with analyses of Hh and BMP function in living cells. Our findings will be integrated with those from developmental and cellular biologists to provide a deeper understanding of these pathways in vivo.

Professor Christian Siebold Professor Christian Siebold

Titles

  • Professor of Structural Biology
  • Cancer Research UK Senior Research Fellow
  • Grant Holding Senior Scientist

Group Information

  • Morphogens and Cell Surface Receptor Signalling

Current Group

  • Rachel Woolley Rachel
    Woolley
  • Oliver Hayward Oliver
    Hayward
  • Tomas Malinauskas Tomas
    Malinauskas
  • Amalie Rudolf Amalie
    Rudolf
  • Benjamin Bishop Benjamin
    Bishop
  • Eleanor Mitchell Eleanor
    Mitchell
  • Samuel Griffiths Samuel
    Griffiths
  • Rebekka Siebold-Schwab Rebekka
    Siebold-Schwab
  • Christiane Kowatsch Christiane
    Kowatsch