22 September 2022
Five world-class teams are set to receive over £19 million from BBSRC to support adventurous research aimed at tackling fundamental questions in bioscience.
Each of these teams - involving 39 investigators from 16 research organisations - will look to advance the frontiers of bioscience knowledge by exploring bold and exciting questions at the forefront of contemporary bioscience.
By pursuing world-class ideas and multidisciplinary research, these projects will convene the people, places, and transformative technologies necessary to tackle complex biological problems from a multitude of perspectives.
The funding through BBSRC’s strategic Longer and Larger (sLoLa) grants programme aims to catalyse ground-breaking collaborations that to advance our understanding of fundamental rules of life, with potentially far reaching implications for agriculture, health, biotechnology, and the green economy.
The five projects aim to:
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Determine how specialised ribosomes regulate gene expression, which could provide insight into how translation goes wrong in certain cancers and other ribosome-linked diseases
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*Discover and improve new plastic-degrading enzymes, which could contribute towards the increasing our capacity to recycle plastic waste
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Understand how bacterial immune systems work, which has the potential to uncover how combinations of natural genome defence systems could be exploited in the fight against anti-microbial resistance
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Establish how light is used to catalyse enzymatic reactions, which could be used to synthesise novel products that heat-activated enzymes are unable to synthesise, such as fuels and other high-value chemicals
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*Learn how an ancient universal membrane repair system functions, which may lead to improvements in the use of bacteria for industrial biotechnology
We are excited to share that two* of these exciting projects involve our colleagues in Biochemistry:
Novel plastizymes
Led by Professor Florian Hollfelder, University of Cambridge
Co-PIs: Professors Christine Orengo, University College London, Rob Finn, EMBL-EBI and Marko Hyvönen, University of Cambridge
The number of new and untested proteins available in metagenomic databases is in the billions and is currently doubling each year. This represents a treasure trove for the discovery of novel enzymes with exciting properties. However, there is a need for better tools to be able to effectively mine these databases and find enzymes of interest.
One group of enzymes which are drawing attention are plastic-degrading enzymes or ‘plastizymes’.
Plastic pollution is a fundamental environmental challenge, an enormous waste of resources, and has the potential to become a major world health issue through the ingestion of micro-plastics. Plastizymes could be used to break down plastic products to enable efficient recovery of raw materials in efficient and environmentally friendly processes.
However, there are currently very few known natural plastizymes and these are relatively inefficient and do not degrade all types of plastic pollutants.
This project, led by Professor Florian Hollfelder, aims to address these limitations by employing a combination of computational and protein engineering approaches to discovering new plastizymes and improving their catalytic ability.
The team will employ a number of cutting-edge technologies. Prof Rob Finn from EMBL-EBI will use machine learning tools to mine a massive metagenomic database MGnify to identify potential new plastizymes. Prof Florian Hollfelder will use microfluidic, ultrahigh throughput screening technologies to experimentally validate these plastizymes and improve their enzymetic properties through directed evolution. Prof Marko Hyvönen will determine three dimensional structures of the new plastizymes and use methods adopted from fragment-based drug discovery to map substrate binding sites on these enzymes. Prof Christine Orengo will develop machine learning methods to identify new plastizymes from three dimensional data.
This will allow them to simultaneously derive generic pipelines for the discovery and directed evolution of novel enzymes, whilst exploiting these pipelines to produce improved plastizymes.
Longer-term, these novel plastizymes could contribute towards the UK’s net-zero ambition by increasing our capacity to recycle plastic waste.
Understanding an ancient universal membrane effector
Led by Professor Gavin Thomas, University of York
Co-PIs: Prof. Kathryn Lilley (University of Cambridge), Dr. Benjamin Willson, Prof. Luke Mackinder, Dr. Jamie Blaza (University of York), Dr. Henrik Strahl (Newcastle University), Prof. Susanne Gebhard (University of Bath), and Dr. Vivien Yeh, Dr. Boyan Bonev (University of Nottingham).
Scientists to go back in time to uncover an ancient process that makes cells resistant to toxic chemicals
Prof. Kathryn Lilley’s group is involved in a BBSRC’s strategic longer and larger (sLoLa) grant scheme to undertake a 5-year project to understand how IM30 proteins, which are found in almost all bacteria and plants, are able to sense and reseal damaged membranes, allowing cells to survive in the presence of a range of stresses. These proteins are known to appear rapidly as ‘first responders’ when the cell membrane becomes damaged and leaky; however, while they are recruited to the membrane, “how they patch up the membrane is unknown, but is likely an ancient sticking plaster that helped early cells become more robust” said lead applicant Prof. Gavin H. Thomas from the University of York.
The project is led by Prof. Thomas and Dr. Benjamin Willson in the Department of Biology, from the University of York, and this grant represents significant new funding to try to unravel the mysterious function of a protein that appears to be able to restore function to damaged cells.
The York team includes Prof. Luke Mackinder’s group in the Centre for Novel Agricultural Products (CNAP), who will study these proteins in photosynthetic microbes where they have important functions in chloroplasts where photosynthesis takes place. The team also includes Dr. Jamie Blaza, from the York Structural Biology Laboratory, Department of Chemistry, who has pioneered the development and application of new technologies that allow real-time measurement of the health status of cells. These tools will be used in conjunction with complementary imaging methods developed by Dr. Henrik Strahl and Prof. Susanne Gebhard at the Universities of Newcastle and Bath, respectively. Additional team members are Dr. Vivien Yeh and Dr. Boyan Bonev at the University of Nottingham, who have developed methods to directly probe the interactions of IM30 proteins with both model and bacterial membranes. Kathryn’s group will apply state of the art membrane proteomics methods to determine context specific interacting partners of the IM30 family proteins and their post-translational modification.
The work builds on a previous project with industry involving Kathryn’s group, which found that this response was activated in diverse bacteria used in biotechnology to manufacture chemicals, and further understanding its function has direct applications in improving bacterial fermentations. The response is also involved in bacterial resistance to some antibiotics and could potentially be targeted to enhance the efficacy of antibiotic treatments.
Professor Melanie Welham, Executive Chair of BBSRC, said: “Long-term support for discovery science is key to delivering the fundamental breakthroughs that keep the UK at the leading edge of bioscience research.
“These five very different projects will each pursue adventurous avenues of investigation at the frontiers of biology by convening the multidisciplinary teams of people, skills and national facilities over the longer timeframes necessary to realise transformational change.
“The projects have huge potential to make underpinning discoveries in the life sciences, which could produce future advances to address global challenges – from tackling plastic pollution to treating cancer – and discoveries with commercialisation potential for biopharma, biotechnology and other industries.”