The SCottish Institute for ceLL Signalling (SCILLS)

Profile

The SCottish Institute for ceLL Signalling (SCILLS) is a new research centre funded by the Scottish Government, which was launched on October 1st 2008. It is based on the 4th floor of the Sir James Black Centre in the College of Life Sciences at the University of Dundee, one floor above the world-renowned Medical Research Council Protein Phosphorylation Unit (MRC-PPU) with which it will interact closely.  The founding Director is Sir Philip Cohen, who is also the Director of the MRC-PPU.  SCILLS is dedicated to understanding how biological processes are controlled and how they become deregulated in disease, with the long-term aim of facilitating the development of improved drugs to treat disease. 

The first Division of SCILLS is a Protein Ubiquitylation Unit (PUU), which studies the role of reversible protein ubiquitylation and related modifications in cell regulation and human disease.  Protein ubiquitylation was discovered in the late 1970s by Avram Hershko and Aaron Ciechanover as a mechanism for marking proteins for destruction by the proteasome, a discovery that won them the Nobel Prize for Chemistry in 2004.  However, we now know that ubiquitylation and related modifications, such as sumoylation and neddylation, have many other functions and that they regulate almost all aspects of cell life.  The potential importance of the ubiquitin system for the development of novel drugs to treat disease was highlighted in 2007 by the approval of the proteasomal inhibitor Velcade for clinical use in treating haematological cancers, the first drug to be developed that exerts its effects by targeting the ubiquitin system. The formation of the world’s first research Unit dedicated to the study of protein ubiquitylation is therefore timely.

The MRC-PPU and several other cell signaling laboratories in the College of Life Sciences have created the world’s leading centre for the study of protein phosphorylation with 200 scientific and support staff working on this topic in the same research complex.  This critical mass of expertise has stimulated important research collaborations that have led to seminal discoveries, such as that between Dario Alessi and Grahame Hardie which identified the tumour suppressor kinase LKB1 as the upstream activator of the AMP-activated protein kinase.  It has also led to the creation of the Division of Signal Transduction Therapy (DSTT), Europe's largest collaboration between academia and the pharmaceutical industry, which has been of great benefit to both parties and has now been in operation for 13 years.

The aim of the PUU is to create a similar critical mass of leading researchers working on the Ubiquitin system in order to stimulate world class research and facilitate the development of biotechnology companies and drug discovery in this area.  These aims will be achieved through the characterisation of key components of the ubiquitin system, such as E3 ubiquitin ligases and deubiquitinases, and by discovering their roles in regulating biological systems relevant to health and disease. Currently the PUU comprises eight research teams supported by an outstanding infrastructure including a DNA Cloning Service, a Protein Production and Assay Development team, an siRNA screening facility and one of Europe’s leading mass spectrometry centres. The PUU also makes use of the many other outstanding facilities in the College of Life Sciences at Dundee.