Experts funded by the Biotechnology and Biological Sciences Research Council (BBSRC) from STFC’s Central Laser Facility (CLF) and Computational Science and Engineering Department (CSED) have solved a puzzle that has confounded scientists for more than 30 years.
The researchers have discovered a previously unknown molecular shape which is partly responsible for transmitting the signals that instruct cells within the body when to grow and divide. It is the uncontrolled growth of cells that causes cancer to spread through the body. Until now, not enough was known about how these molecules, known as epidermal growth factor receptors (EGFRs), transmit messages in the development of cancer. This means drugs designed to stop them transmitting these cancer-inducing signals have also been limited in their effectiveness.
Project leader Dr Marisa Martin-Fernandez, a CLF scientist based at the Research Complex at Harwell (RCaH), says: “A number of drugs aim to limit EGFRs’ role in spreading cancer but because human EGFRs haven’t been well understood, the drugs are designed simply to block every signal they transmit. But the human body is good at compensating for losses of function so it finds ways of bypassing blocked receptors to allow cancerous cells to grow again. Unfortunately the current drugs therefore all too often only provide temporary remission.
“Our breakthrough will provide a better platform of knowledge on structure variation of EGFRs in vivo. Potentially this enables the pharmaceutical industry to develop drugs that target EGFRs’ cancer-related functions more specifically but also allow the receptors to go on performing other tasks. This makes it less likely that the body will try to compensate for total loss of function.”
Peter Parker is the Principal Investigator at King’s College London on this work. Dr George Santis, also from King’s College London, is a consultant in respiratory medicine and will help take this work forward. He said: “Translating knowledge derived from scientific research into successful clinical therapies is exemplified by EGFR and its dysregulation in cancer. The use of new biologicals that inhibit EGFR has proved transformational in managing solid tumours particularly lung cancer where conventional anti-cancer treatment reached a plateau. There is however still much we don’t understand regarding EGFR and its role in malignancy; this breakthrough provides the foundation for novel ways to assess EGFR in cells and tissues that may lead to new insights on how to target EGFR to treat human cancers”.
The team has also shown that this shape shares key features with the better understood EGFR molecules in fruit flies, providing clues on how EGFRs have changed during evolution.
Dr Martyn Winn of the CSED at STFC’s Daresbury Laboratory says: “The key has been close collaboration between the experimental and computational teams involved. The CLF used its OCTOPUS facility to take nanoscale measurements of EGFRs in cells. We took the measurements and used high performance computing (HPC) to calculate the receptors’ high-resolution structure, allowing us to determine their similarities with the fruit fly EGFRs.”
Professor John Collier, Director of the CLF, says: “Breakthroughs like this have the potential to really pay dividends in terms of saving lives and maximising the value of healthcare expenditure. By constantly pushing forward the boundaries of what laser technology can do, we can deliver real-world benefits that tangibly improve people’s lives.”
Details of the breakthrough are presented in the paper ‘Human EGFR aligned on the plasma membrane adopts key features of Drosophila* EGFR asymmetry’, and are featured on the front cover of the current edition of the journal Molecular and Cellular Biology published today.
The image from the front cover of the journal as well as scientists working in the Central Laser Facility, are available. Please contact the STFC Press Office for more details (see external contact below).
Notes to editors
The BBSRC award is a £5.2M ‘LoLa’ (longer and larger) grant secured jointly by STFC and King’s College London in 2009. The research summarised in this release represents just one aspect of the work being supported by this funding.
OCTOPUS (Optics Clustered to Output Unique Solutions) is a new concept in laser imaging, in which multiple light sources are linked to multiple imaging stations allowing a combination of techniques to be brought to bear on the samples under investigation.
*Drosophila is the Latin name for the fruit fly. Fruit flies are often used in biology to understand more about the inner workings of cells.
Dr George Santis is also head of department at the Asthma Allergy and Respiratory Science School of Medicine at King’ College London.
Computational Science and Engineering Department www.cse.scitech.ac.uk
About STFC’s Central Laser Facility
STFC’s Central Laser Facility is based at the RCaH (see below). More information can be found here: www.clf.rl.ac.uk
About the Research Complex at Harwell
The Research Complex at Harwell (RCaH) is a new multidisciplinary laboratory that provides facilities enabling researchers to undertake cutting-edge, innovative scientific research in the life and physical sciences and at the interface between them. The RCaH is open, on a competitive basis, to research teams from UK universities, as well as to Diamond and Rutherford Appleton Laboratory (RAL) staff. The Medical Research Council is leading the project on behalf of Research Councils UK (RCUK), in partnership with the BBSRC, the Engineering and Physical Sciences Research Council (EPSRC), the Natural Environment Research Council (NERC), the STFC and Diamond. More information can be found here: www.rc-harwell.ac.uk
About King’s College London
King’s College London is one of the top 25 universities in the world (2010 QS international world rankings), The Sunday Times ‘University of the Year 2010/11’ and the fourth oldest in England. A research-led university based in the heart of London, King’s has nearly 23,500 students (of whom more than 9,000 are graduate students) from nearly 140 countries, and some 6,000 employees. King’s is in the second phase of a £1Bn redevelopment programme which is transforming its estate.
King’s has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450M.
The Science and Technology Facilities Council is keeping the UK at the forefront of international science and tackling some of the most significant challenges facing society such as meeting our future energy needs, monitoring and understanding climate change, and global security.
The Council has a broad science portfolio and works with the academic and industrial communities to share its expertise in materials science, space and ground-based astronomy technologies, laser science, microelectronics, wafer scale manufacturing, particle and nuclear physics, alternative energy production, radio communications and radar.
STFC operates or hosts world class experimental facilities including:
- in the UK; ISIS pulsed neutron source, the Central Laser Facility, and LOFAR. STFC is also the majority shareholder in Diamond Light Source Ltd.
- overseas; telescopes on La Palma and Hawaii
It enables UK researchers to access leading international science facilities by funding membership of international bodies including European Laboratory for Particle Physics (CERN), the Institut Laue Langevin (ILL), European Synchrotron Radiation Facility (ESRF) and the European Southern Observatory (ESO).
STFC is one of seven publicly-funded research councils. It is an independent, non-departmental public body of the Department for Business, Innovation and Skills (BIS). www.stfc.ac.uk
BBSRC is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £470M in a wide range of research that makes a significant contribution to the quality of life in the UK and beyond and supports a number of important industrial stakeholders, including the agriculture, food, chemical, healthcare and pharmaceutical sectors.
BBSRC provides institute strategic research grants to the following:
- The Babraham Institute
- Institute for Animal Health
- Institute of Biological, Environmental and Rural Sciences (Aberystwyth University)
- Institute of Food Research
- John Innes Centre
- The Genome Analysis Centre
- The Roslin Institute (University of Edinburgh)
- Rothamsted Research
The Institutes conduct long-term, mission-oriented research using specialist facilities. They have strong interactions with industry, Government departments and other end-users of their research.
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