Sixty years after Francis Crick predicted the central importance of protein synthesis, a new project aims to shed light on how it is controlled

  • 30
  • SEP
  • 2019

Rothamsted is to lead one of four UK consortia awarded a total of £14M to explore the fundamental biology of living systems, with the project set to be the biggest study into protein regulation ever attempted. 

Also involving University College London and the University of Cambridge, the BBSRC-funded project will use ‘-omic’ technologies and Big Data analysis to decipher the rules governing the regulation of protein abundance in plants. 

Protein regulation underpins many important agricultural traits with the two so-called ‘green revolutions’ - which resulted from the development of dwarf wheat and flood-tolerant rice varieties - being prime examples. 

Project lead Professor Freddie Theodoulou said despite it being more than six decades since Francis Crick proposed his Central Dogma of molecular biology - which states that information flows from DNA to RNA to protein - scientists still don’t fully understand how this process is controlled. 

She said: “This project provides a fantastic opportunity to tackle the important question of how plant proteins are regulated. 

“Plants are constantly producing, using and recycling proteins. Changes to the proteins in plant cells can have huge implications, affecting a cell’s size or role, and altering the plant’s nutritional value or response to environment changes. 

“For cells to work efficiently, proteins need to be produced in the right place, at the right time and in the right amount, and removed when no longer needed. There are many levels at which this process is regulated and there are still many gaps in our knowledge. 

“Our project seeks to use the model plant, Arabidopsis thaliana, to answer fundamental questions about the control of protein expression, including which mechanisms are important, and how they interact in a complex multi-cellular organism.” 

The team also aims to determine to what extent the protein content of a given cell, tissue or organ predicts observable traits, or phenotype, of the plant – which will be of great interest to commercial plant breeders. 

To address these questions, the group has designed an integrated programme of experiments and sophisticated mathematical analysis around a genetically variable “MAGIC” population of Arabidopsis

Multiparent Advanced Generation Inter-Cross (MAGIC) lines were created to improve methods of identifying the genetic variants that underlie observable traits. 

In total, these lines represent a large amount of natural genetic variation, but pinpointing the genes responsible for specific traits is much easier. 

Funded through the BBSCR’s strategic Longer Larger (sLoLa) grants call, the hope is to unpick the multiple regulatory layers between chromatin and protein, where knowledge of their relative importance and how they interact is incomplete. 

Professor Theodoulou said: “We expect to generate and test new hypotheses in the lifetime of the project but it’s also our vision to share the rich datasets and methodology that we will produce with the research community via our Knetminer knowledge resource. 

“We think this project has an important role to play in maintaining the UK’s leading position not just in plant science but also basic biology in general. To the best of our knowledge, no-one has attempted such a comprehensive a study on protein regulation, even in the medical world.” 

In addition to Rothamsted staff, Professor Kathryn Lilley, from the University of Cambridge, UCL's Professor Richard Mott, and Dr Gancho Slavov at Scion Research in New Zealand, will also be leading groups working on the new project.

Announcing which project bids had been succesful, BBSRC’s Executive Chair, Professor Melanie Welham, said the funding call was all about pushing forward the boundaries of knowledge, to make unexpected and potentially world changing discoveries. 

“These four projects are supporting interdisciplinary teams, underpinning the importance of collaboration when tackling such complex questions. This investment continues our long-standing commitment to excellence in discovery research that has helped position the UK as a leading nation in bioscience."

About Rothamsted Research
Rothamsted Research is the longest-running agricultural research institute in the world. We work from gene to field with a proud history of ground-breaking discoveries, from crop treatment to crop protection, from statistical interpretation to soils management. Our founders, in 1843, were the pioneers of modern agriculture, and we are known for our imaginative science and our collaborative influence on fresh thinking and farming practices.
Through independent science and innovation, we make significant contributions to improving agri-food systems in the UK and internationally. In terms of the institute’s economic contribution, the cumulative impact of our work in the UK was calculated to exceed £3000 million a year in 20151. Our strength lies in our systems approach, which combines science and strategic research, interdisciplinary teams and partnerships.
Rothamsted is also home to three unique resources. These National Capabilities are open to researchers from all over the world: The Long-Term Experiments, Rothamsted Insect Survey and the North Wyke Farm Platform.
We are strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), with additional support from other national and international funding streams, and from industry. We are also supported by the Lawes Agricultural Trust (LAT).
For more information, visit; Twitter @Rothamsted
1Rothamsted Research and the Value of Excellence: A synthesis of the available evidence, by Séan Rickard (Oct 2015)

The Biotechnology and Biological Sciences Research Council is part of UK Research and Innovation, a non-departmental public body funded by a grant-in-aid from the UK government.
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, BBSRC invested £469 million in world-class bioscience in 2016-17. 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.
More information about BBSRC, our science and our impact.
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About LAT
The Lawes Agricultural Trust, established in 1889 by Sir John Bennet Lawes, supports Rothamsted Research’s national and international agricultural science through the provision of land, facilities and funding. LAT, a charitable trust, owns the estates at Harpenden and Broom's Barn, including many of the buildings used by Rothamsted Research. LAT provides an annual research grant to the Director, accommodation for nearly 200 people, and support for fellowships for young scientists from developing countries. LAT also makes capital grants to help modernise facilities at Rothamsted, or invests in new buildings.