The four teams will tackle bold challenges at the frontiers of bioscience, combining world-class ideas, people and transformative technologies with the aim of uncovering fundamental rules of life.
Harnessing team science
By taking a coordinated, interdisciplinary approach, the teams hope to make major breakthroughs that would not be possible through individual research efforts alone.
The challenges the teams hope to address include:
- elucidating the rules that govern microbial communities
- determining how the human heart develops
- resolving the link between structure and function of cell-surface sugar biomolecules
- understanding the mechanisms of bacterial cell wall synthesis
The investment from the Biotechnology and Biological Sciences Research Council’s (BBSRC) strategic Longer Larger (sLoLa) grants programme aims to catalyse and convene the critical mass of research effort needed to address significant fundamental questions in bioscience.
A pivotal step for frontier bioscience
Professor Guy Poppy, Interim Executive Chair at BBSRC, said:
The latest investment by BBSRC’s sLoLa award programme represents a pivotal step in advancing frontier bioscience research.
These four world-class teams are poised to unravel the fundamental rules of life, employing interdisciplinary approaches to tackle bold challenges at the forefront of bioscience.
By fostering collaboration and innovation, we aim to catalyse ground-breaking discoveries with far-reaching implications for agriculture, health, biotechnology, the green economy and beyond.
The projects
Rules of life in microbial communities
Led by Professor Sophie Nixon, The University of Manchester.
Microbial communities, often called microbiomes, are found in almost every habitable environment on the planet. They exert a significant influence on each of these environments, whether that be the soil that we grow our food in or the guts of animals.
Recent technological advances have allowed researchers to begin to study the interactions between members of microbiomes for the first time. However, we have barely scratched the surface of resolving how these interactions affect the structure, function, and stability of the community as a whole.
Drawing on the low-diversity communities inhabiting geothermal springs, and using a powerful combination of biochemical, ‘omics and synthetic biology approaches, this project seeks to uncover the rules that govern microbial life in communities.
Further, the team aim to engineer this microbial community both as a learning tool with which to test emerging hypotheses and as a testbed for future biotechnological development.
By unravelling the rules of life in this tractable model system, this project will take the first major step toward understanding the complex microbial communities that impact numerous aspects of human life.
Ultimately, this may facilitate the engineering of bespoke microbial communities to be used for a plethora of important applications. This includes new ways to bio-convert CO2 emissions into socio-economically beneficial compounds, contributing toward a more sustainable and net zero future.
This project is a collaboration between The University of Manchester and the Earlham Institute. It is led by Sophie Nixon in collaboration with:
- Rainer Breitling
- Michael Brockhurst
- Duncan Cameron
- Katharine Coyte
- Rosa Cuellar Franca
- David Johnson
- Andrew Pitt
- Christopher Quince
- Eriko Takano
Human heart development
Led by Professor Sanjay Sinha, University of Cambridge.
The heart is made up of lots of different cells. How all these different cell types get produced, how they come together and how they communicate with one another to form a healthy human heart is not fully clear at present.
Most of what we currently know about heart development comes from work in model organisms such as the mouse and zebrafish. However, despite morphological similarities, the human heart differs to other vertebrate hearts in developmental timelines, physiology, and cellular function.
This makes it essential to understand which of the key molecular events that regulate heart formation are truly conserved across vertebrates, and which are human-specific.
This project will combine state-of-the-art single-cell and spatial transcriptomics using cutting-edge bioinformatics to generate a heart developmental atlas at unprecedented spatial and temporal resolution.
The team will then leverage this atlas alongside stem cell studies to determine the critical molecular regulators of events during human heart development. Then how these may differ to other vertebrates, and how scientists may better recreate the heart using stem cells.
These studies will transform our understanding of cardiac development in humans. Moreover, they will provide a potential template for similar studies of other major organs in the body.
This project is a collaboration between University of Cambridge, University of Oxford and Wellcome Trust Sanger Institute. It is led by Sanjay Sinha in collaboration with Vincent Knight-Schrijver, Paul Riley, Filipa Simõnes, Sarah Teichmann and Richard Tyser.
GlycoWeb
Led by Professor Cathy Merry, University of Nottingham.
Glycosaminoglycans (GAGs) are a class of biomolecules that decorate the surface of virtually all cells in the body as well as being found in the ‘matrix’ between cells. They have been shown to play critical roles in a multitude of biological processes, including cell signalling and development and host-pathogen interactions, being often dysregulated in disease.
Despite their ubiquity and importance, we do not fully understand how GAG biosynthesis is controlled by cells, nor how the molecular structure of most GAGs links to their biological function. To compound this problem, there is currently a lack of tools with which to detect and characterise GAGs in tissues and on cells.
The team assembled for this project will set about addressing these knowledge gaps using an ambitious multidisciplinary approach, integrating analyses at the transcriptional through to the multicellular level.
They will make use of cutting-edge animal-alternative approaches developed through prior National Centre for the Replacement, Reduction and Refinement of Animals in Research (NC3Rs) support.
These include 3D models of development known as gastruloids which will be used to determine how changes in GAG structures affect the signalling pathways driving early development. Further, the team will take advantage of innovation in non-animal derived antibody technologies to create new panels of GAG-binding probes.
These research efforts will allow the team to elucidate the rules that govern the relationship between GAG structure and function. As well as impacting a diverse range of bioscience disciplines, this new knowledge may pave the way for the identification of targets for therapeutic intervention in diseases such as cancer.
This project is a collaboration between University of Nottingham, University of Liverpool, The University of Manchester and The Francis Crick Institute, with support from University of Copenhagen, University of Georgia and InterReality Labs.
It is led by Cathy Merry in collaboration with:
- Kenton Arkill
- Anthony Day
- Claire Eyers
- Kevin Gough
- Andrew Hook
- Naomi Moris
- David Turner
Bacterial cell wall formation
Led by Professor David Roper, University of Warwick.
The bacterial cell wall is essential for the survival of most bacteria. It is also what dictates their shape.
Bacterial cell walls are comprised mostly of a compound called peptidoglycan which is polymerised to form new wall material by a multiprotein complex known as the ‘elongasome’.
Remarkably, we know very little about how this important protein complex functions at a molecular level. This represents a key knowledge-gap in our understanding of bacterial physiology.
Through a coalescence of microbial biochemistry, biophysics, and chemical biology, the team leading this project aim to provide new insight into how the bacterial cell wall is formed.
They will deploy structural analyses in tandem with molecular dynamics simulations to determine the basis of elongasome function and regulation from the atomic through to the macromolecular scale.
This will lead to a significant advance in our understanding of bacterial cell wall synthesis and morphogenesis.
Further, this project may lay the foundations for development of fundamentally new classes of antibiotics that inhibit the elongasome machinery.
This project is a collaboration between University of Warwick and Queen’s University Belfast. It is led by David Roper in collaboration with Stephen Cockrane, Séamus Holden and Phillip Stansfeld.
About the sLoLa programme
Advancing our understanding of the rules of life is a key priority as outlined in BBSRC’s strategic delivery plan.
The large-scale support offered via the sLoLa awards programme enables world-class teams to pursue innovative avenues of multidisciplinary investigation over the longer timeframes necessary to realise transformational change.
By encouraging researchers to pursue bold and creative questions, BBSRC aims to catalyse exciting fundamental bioscience discoveries that may have far reaching implications for agriculture, health, biotechnology and the green economy.
The power of sLoLa
Professor Ross Anderson is principal investigator of the ‘circuits of life’ sLoLa project led by the University of Bristol.
Commenting on the impact of BBSRC’s sLoLa funding, Professor Anderson said:
It was at our recent circuits of life team meeting that we fully realised the scale of what we have been able to build with our sLoLa funding.
This is both in people power and the breadth of the research in which we are engaging. It’s hard to see how we could have achieved this with simultaneous standard research grants.
Read more about how Professor Anderson is leveraging the power of team science in his 2022 blog.
This is the fifth sLoLa funding round since the scheme relaunched in 2018 and brings its total investment to approximately £81 million. BBSRC plans to invest up to a further £20 million in a sixth round which is currently ongoing.
Top image: Credit: nicolas_, E+ via Getty Images