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Major new projects to reveal fundamental rules of life

The Biotechnology and Biological Sciences Research Council (BBSRC) has awarded £14M to researchers in the UK to work on four new large-scale projects. This leading edge discovery research, funded through the strategic Longer Larger (sLoLa) grants call, aims to make major advances in our understanding of the fundamental biology of living systems.

BBSRC’s Executive Chair, Professor Melanie Welham, said, “Frontier Bioscience is all about pushing forward the boundaries of knowledge, often making 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.”

BBSRC’s vision is to push back the frontiers of biology to deliver a healthy, prosperous and sustainable future. These curiosity-driven projects continue our ongoing commitment to excellence in discovery research across the breadth of our remit, from molecules to systems. This investment through its Strategic Longer and Larger call advances this strategy for UK bioscience by furthering the revolution unfolding in our understanding of living systems, driven by new tools, technologies and interdisciplinary approaches.

Each project brings together multidisciplinary teams to tackle significant fundamental scientific questions about antibody specificity, the extracellular matrix, protein abundance in plants and RNA splicing. The funding will enable teams of UK scientists to push the frontiers of human knowledge and make breakthrough discoveries that can eventually be harnessed to benefit our everyday lives.

The projects are:

Mapping antibody class switch mechanisms and function

How do antibodies switch their function? Antibodies are amazingly versatile molecules. They are produced by the immune system to target pathogens and can also be manufactured to treat diseases including cancer. Antibodies are highly variable so they can recognise billions of different molecules but they also have invariable segments (constant regions) that determine the antibody function in the immune system. This project will reveal how switching of these constant regions is controlled.

This project is a collaboration between researchers at King’s College London, University College London and the University of Surrey, led by Professor Franca Fraternali, Kings College London. Professor Fraternali said “This investment will enable us to understand the mechanisms and consequences of changing constant regions in the antibody structure, with exciting implications for the design of new drugs or vaccines.” 

Opportunities to modulate extracellular matrix secretion and assembly for long term health

How do our cells hold themselves together? Cells are the fundamental building block of living organisms but rely on an extracellular matrix to provide structure and protect them from environmental forces. Without this matrix connective tissues such as skin, tendon and cartilage would be nothing but an amorphous slurry. By unravelling the fundamental rules which govern how the matrix is maintained and repaired throughout a healthy life course, this project has the potential to improve treatment strategies for wound healing and age-related matrix diseases like osteoarthritis.

This project is a collaboration between researchers at University of Manchester and University of Bristol, led by Professor Karl Kadler, University of Manchester. Professor Kadler said “Advances in understanding how tissues develop, are maintained, repaired and age, requires the collective effort of a multidisciplinary team of molecular cell biologists, immunologists, biochemists, circadian clock biologists, wound healing experts and mathematicians, for the benefit of the health science strategy across UKRI, charity funders, and industry.”

What determines protein abundance in plants?

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. This project will decipher the fundamental rules governing the regulation of protein abundance in plants, and promises new resources which may be exploited by crop breeders in the future.

This project is a collaboration between researchers at Rothamsted Research, University of Cambridge and University College London, Led by Professor Frederica Theodoulou, Rothamsted Research. Professor Theodoulou said "This sLoLa project provides a fantastic opportunity to tackle the important question of how proteins are regulated, which underpins all agronomically important traits."

How do RNA-binding proteins control splice site selection? 

How does one gene produce different proteins? Splicing is the process of editing information from a gene, while it is in the form of RNA, before it produces proteins. In mammals, splicing enables the production of different versions of proteins from a single RNA sequence. By revealing the fundamental mechanisms controlling splicing at the single-molecule level, this project will allow us to better understand this complex process, reveal opportunities for novel therapies that re-direct it and yield clues for how splicing might be manipulated to design synthetic genes in the future.

This project is a collaboration between researchers at University of Leicester, University of Glasgow and University of Strathclyde, led by Professor Ian Eperon, University of Leicester. Professor Eperon said “'We chose the BBSRC because it supports fundamental science that pushes forward the frontiers of knowledge, which is incredibly important to underpin innovation in science and its applications more generally.''