The city of Leeds has an enviable history as the home of world-leading scientific advances in the field of molecular biology – now Professor Sheena Radford and her team of researchers are on course to write yet another chapter.
The UK’s leading scientific academy, the Royal Society, has today announced that it is awarded Prof Radford, who is director of the Astbury Centre for Structural Molecular Biology at the University of Leeds, one of its most prestigious research professorships for a five-year project that could transform mankind’s understanding of neurodegenerative diseases like Alzheimer’s and Parkinson’s.
The work will develop new ways of ‘seeing the unseen’ – the way proteins interact to shape or destroy memories.
A new research hub, known as the Centre for Dynamic Disease Mechanisms at Leeds, is being formed at the Astbury Centre to develop new techniques that will allow scientists to visualise protein interactions and thereby offer new insight into one of the biggest unanswered questions in biology; the exact role a protein structure called amyloid has in both building lifelong memories and also in their destruction when diseases strike.
Speaking over Zoom ahead of the Royal Society announcement, Prof Radford explains: “It is a new era for science where we hope we will be able to look at proteins moving in real time and space in living cells. If we can do that, in the longer term we will be able to make better therapies that target proteins as moving entities.”
There are tens of thousands of proteins in the human body, which come together in fleeting interactions to carry out the vital chemical and signalling processes necessary for life such as movement and breathing. As Prof Radford puts it, they are quite simply “the workhorses of life”.
But when problems occur with protein formation, the consequences for an individual can be dire. For a protein to function, it needs to fold into a particular shape.
An amyloid structure can form when a protein fails to fold properly in the process of acquiring its three-dimensional structure and forms clumps or fibrils.
Prof Radford explains: “Proteins misfold all the time. When folding goes wrong, the cell normally gets rids of bad proteins like a quality control check on a car production line. But if the quality control doesn’t work as well when you get older and proteins start to misfold more, that gives rise to horrible diseases like Alzheimer’s and Parkinson’s.”
While the process of how these amyloid formations cause disease is not fully understood, in recent years scientists have made another intriguing discovery - that some fibrils can actually be good for you and play a key role in the healthy cell functioning that allows for the creation and retention of long-term memories.
Until now, scientists have been unable to see and understand the fleeting interactions of both positive and negative amyloid assemblies so they can be fully understood.
The new project aiming to do just that builds on not just years of research from Prof Radford and her colleagues in this area, but other pioneers in molecular biology connected to Leeds.
The 1915 Nobel Prize in Physics was awarded to Sir William Bragg, who was the Cavendish Professor of Physics in Leeds, and his son William Lawrence Bragg for their work in developing the field of X-ray crystallography. Among other purposes, the method for determining the atomic and molecular structure of a crystal helped reveal the structure and function of proteins.
Bragg’s work was then built upon by William Astbury, who coined the term ‘molecular biology’ during his long research career at the University of Leeds between the 1920s and 1960s. Astbury pioneered the use of X-rays to explore the structures of living systems to the extent that Nobel Prize winning Austrian scientist Max Perutz once hailed Astbury’s laboratory in Leeds as “the X-ray Vatican”.
Prof Radford, who joined the University of Leeds in 1995 and was appointed as director of The Astbury Centre (which is named after her predecessor) in 2012, says she is honoured to be continuing the university’s pioneering work in this field.
“What Astbury and Bragg did was taking proteins out of cells so we could see them,” she explains. “The next big frontier is to look at them as moving entities but back in cells – then we will be able to develop therapies for disease. It is like trying to hit a moving target in a crowd.
“If we are able to hit these moving targets we will be able to understand what life is, what memory is, what keeps us healthy. It will also let us think about clever ways of stopping us getting sick.
“Everyone gets more forgetful as you get older, that is the normal ageing process. But some people then get Alzheimer’s or Parkinson’s really rapidly. We need to understand why that happens to get treatment right.”
The Royal Society’s recognition builds on existing research done at The Astbury Centre, which brings together researchers from the fields of biological sciences, physical sciences and medicine.
Its twin Titan Krios electron microscopes, which have been in place since 2016 and operate around the clock, are powerful enough to see individual atoms in proteins.
In 2018, the Nature Communications journal published research carried out at the centre which revealed amyloid proteins have a more complex shape than previously thought and vary with each disease they cause.
Last October, Prof Radford was awarded an OBE for her work in the field of molecular biology, while she has also earnt a raft of scientific prizes and honours across the course of her career.
She says she has reached this point in her career by what she describes as ‘following my nose’ and seeing where engaging with her passion and enduring lifelong fascination with proteins will take her.
“I was always interested as a schoolgirl in the chemistry of life – questions like why does eating cornflakes give you energy and how do muscles work? I realised biochemistry was what I wanted to do at a very early age,” she says.
“I went to Birmingham University to study biochemistry and I realised what I loved was proteins.”
She says it is a true privilege to work in a field that seeks to understand the mechanics behind things like the nature of memory. “It is really the most fascinating question about life and humanity.”
But she is keen to stress the research she is involved in is very much a team effort.
“I just love my job, working with fantastic people, young students and post-docs from around the globe. I say I have been 20 all my life because I have always worked with people of that age. It has been my life’s work to build The Astbury Centre with brilliant colleagues. There is no way this would have happened with me on my own.”
Work ‘will open new chapter in biology’
Professor Radford’s achievement will “open a new chapter in biology”, says the vice-chancellor of the University of Leeds.
Professor Simone Buitendijk, Vice-Chancellor of the University of Leeds, says: “The award from the Royal Society is a recognition of the huge advances that Professor Radford and her team have made in understanding the structural and molecular basis of life.
“There aren’t many scientists who can say their research is opening up a new chapter in biology, but that is exactly what Professor Radford will be doing and I am proud that Leeds and the Astbury Centre is at the heart of that endeavour.”
The award is one of seven Royal Society Research Professorships being granted this year.
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