All our cells contain all our genes, but for our cells to perform different functions, they must activate different genes.This is called gene expression.  Genes are controlled by genetic switches called enhancers. The arrangement of these enhancers throughout the genome has been well conserved throughout evolution over hundreds of millions of  years,suggesting that fundamental rules control their arrangement. Researchers refer to these as ‘enhancer semantics’, also sometimes known as the ‘grammar’ of DNA. The grammar metaphor refers to rules about enhancers: what factors are present which can switch them on or off and in what number, order, orientation, spacing and affinity. 

Boris leads the Computational Regulatory Genomics group at the LMS and is Professor of Computational Biology at Imperial College London. He’s part of a project called the ‘semantic rules of gene regulatory landscapes’, led by Ferenc Mueller at the University of Birmingham. The team also includes scientists from the University of Edinburgh, the University of Manchester, the Francis Crick Institute, and the European Bioinformatics Institute, bringing together expertise in multi-omics, genome engineering and synthetic genomics tools.  

The team will tackle the rules underlying enhancer semantics. Using a combination of computational and wet lab techniques, they aim to uncover how these rules control the development of vertebrates and gene expression more broadly. 

When enhancer semantics goes wrong – because of mutations that “break” enhancer switches, scramble their order, or put them in contact with wrong genes – many diseases can occur, including cancer and developmental disorders.By better understanding the rules that dictate gene expression, researchers could develop more effective therapies for these conditions in the future. 

About the Strategic Longer and Larger (sLoLa) grant scheme 

This funding scheme supports projects that could achieve major breakthroughs in our understanding of living systems. What makes these grants different from many other schemes is their focus on team science and long-term planning. The projects funded by the sLoLa programme have long-term goals that, if accomplished, will push science forward by opening new avenues of research. 

Two other researchers from Imperial received grants in the latest round of funding, showcasing the breadth of innovative work happening within our wider research community: 

• Bill Rutherford, from the Department of Life Sciences in the Faculty of Natural Sciences, is leading a team who will tap into the unseen light of photosynthesis. 

• Andrew Edwards, from the Department of Infectious Disease in the Faculty of Medicine, is part of a team led from the University of Birmingham who will gain a better understanding of antibiotic resistance at its roots.