New technique for developing drugs to treat serious illnesses

Posted by er134 at Nov 15, 2013 09:15 AM |
Researchers exploit the power of evolution to create designer proteins

Issued by University of Leicester Press Office on 15 November 2013

Contact pressoffice@le.ac.uk to request images

An international team of researchers led by the University of Leicester has “harnessed the power of evolution” to create a new drug for possible use against heart disease, inflammation and other illnesses.

Researchers in the Department of Cardiovascular Sciences and Department of Biochemistry at the University of Leicester, together with colleagues in Cambridge, the USA and Italy, have employed a new technique to create protein-based drugs.

According to Professor Nick Brindle, the lead researcher: “This technique harnesses the power of evolution to engineer specific functions into a protein, such as the ability to neutralise a toxin or to activate healing.

“This involves making a particular cell type generate millions of different variants of our protein, selecting the variants that have improved properties and then repeating the cycle until the protein has been changed to a form with the exact properties we want.”

To show how the method works, the group took a protein normally found in the body and evolved it into a form that can block a molecule involved in blood vessel growth and inflammation.

This new protein, called a ligand-trap, is now being developed as a potential therapeutic for treating heart disease, inflammation and other illnesses.

Said Professor Brindle: “The idea that you can evolve proteins into forms that do what you want is not new, but it has been very difficult to do this for many of the complex proteins that we want to use as drugs or for other applications.

“This new approach promises to make engineering of such proteins not only possible but relatively easy. In addition to medicine, these specifically evolved ‘designer proteins’ have a wide range of applications in the chemical, pharmaceutical, and agricultural industries.

“This is a big step forward. We are hoping that, over the next five years or so, this new protein can be developed into a form that could be used to treat inflammation and other conditions.”

The work, being published in the Journal of Biological Chemistry, was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), MRC and the Wellcome Trust. The Leicester team collaborated principally with Dr Julian Sale at the MRC Laboratory of Molecular Biology in Cambridge, with additional input from Dr Hiroshi Arakawa in Italy and Dr Jean-Marie Buerstedde at Yale.

Professor Brindle said: “We are really excited about getting this technique to work and are already using it to make other new molecules that we think will be useful to people. It was a real bonus for us to be able to evolve the ligand trap using the technique as this trap targets a molecule that is involved in a whole range of health problems.”

Ends

Notes to editors

For more information please contact Professor Brindle at: npjb1@mail.cfs.le.ac.uk

URL: http://www.jbc.org/content/early/2013/10/08/jbc.M113.510578.abstract.html

This is a pre-publication version; the final version will be published in the November 15th issue

Journal of Biological Chemistry volume 288, pages 33205-33212.

Directed Evolution of an Angiopoietin-2 Ligand Trap by Somatic Hypermutation and Cell Surface Display

Brindle, NP, Sale JE, Arakawa, H, Buerstedde, JM, Nuamchit T, Sharma, S & Steele, KH.

About BBSRC

The Biotechnology and Biological Sciences Research Council (BBSRC) invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.

Funded by Government, and with an annual budget of around £467M (2012-2013), we support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.

For more information about BBSRC, our science and our impact see: http://www.bbsrc.ac.uk

For more information about BBSRC strategically funded institutes see: http://www.bbsrc.ac.uk/institutes

 

The Medical Research Council has been at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Twenty-nine MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. www.mrc.ac.uk The MRC Centenary Timeline chronicles 100 years of life-changing discoveries and shows how our research has had a lasting influence on healthcare and wellbeing in the UK and globally, right up to the present day. www.centenary.mrc.ac.uk

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.

www.wellcome.ac.uk

Share this page: