Project seeks membrane protein breakthrough
drug treatments for diseases including cancer, parasitic, bacterial
and viral diseases by visualising, in detail, membrane proteins
that have the potential to be novel targets.
The project represents an additional tool to aid in the design of new drug treatments. Currently, about half the drugs that are used to treat these disorders use membrane proteins as drug targets. However, in designing effective drugs, the pharmaceutical industry has essentially been researching blind, unable to visualise the target.
Researchers from the University of Sheffield have been taking part in the Membrane Protein Structure Initiative consortium (MPSI), a group of experienced membrane research groups at universities and institutes across the UK backed by funding worth £6.8m from the Biotechnology and Biological Sciences Research Council (BBSRC)
Lead researcher Professor Per Bullough and his research group will be tackling the membrane protein samples which structure is unable to be determined by techniques used at the other research centres.
Many membrane proteins are unstable outside their natural environment but, using advanced electron microscopy, the Sheffield team can mimic this natural environment and keep the proteins stable for long enough to be visualised.
Additional members of the consortium include The University of Manchester Institute of Science and Technology (UMIST), whose role is working towards the structure determination of a class of membrane proteins called ABC-transporters. The 5-year project will be carried out within the Manchester Interdisciplinary Biocentre after its inception in the summer of 2005.
Bullough said: "Thanks to the human genome project we know the instructions that govern the structure of membrane proteins, but those instructions are written in code. We still know very little about the way that code is used to build a three dimensional shape."
"This collaborative project aims to determine the proteins' shapes using a range of analytical methods. Following on from the human genome project it's one of the next big steps forward for novel drug treatments."
Membrane proteins provide a range of functions that are essential for a healthy cell. Over 30 per cent of human genes produce membrane proteins and more than half of the drugs in current use act on them, making them prime targets for structural studies. Despite their importance, relatively little is known about the structures of membrane proteins, or the ways in which they carry out their functions.
Indeed, to study the way they work an understanding of their structure is needed at the atomic level,
However this cannot be achieved without removing them from the membrane they are bound to for study on a powerful X-ray source. In addition it is very difficult to produce large quantities of active membrane proteins for structure determination.
In commenting on the work of the consortium BBSRC chief executive, Professor Julia Goodfellow said: "The sequencing of a large number of genomes has provided us with a wealth of information but has raised many challenging questions about the function of proteins within cells."
"The programme is aimed at understanding the function of important groups of proteins at the molecular level."
Additional members of the consortium include research groups from the Universities of Glasgow, Leeds, Oxford and Imperial College.
