Researchers receive funding to explore cell division puzzle

A project involving Professor Bill Earnshaw has been awarded €10.3million funding by the European Research Council to explore the changes that occur as DNA is packaged into compact chromosomes during cell division.

Cell dividing

The European Research Council (ERC) Synergy grants are awarded to research teams to solve science’s toughest puzzles across a broad range of fields.

Bill’s project, in collaboration with Universities of Zurich and Massachusetts, will use advanced techniques to explore how DNA is packaged and reorganised during the process of chromosome formation as cells enter division. 

The process of mitosis – in which a single cell divides into two identical daughter cells – has been studied for over 140 years, revealing how DNA, packaged into chromosomes, duplicates and divides.

Before cells divide our genetic material is contained in long thread-like structures, known as chromatin, which is made up of DNA and proteins that allow it to be packaged to fit inside the cell.

But how chromosomes, containing our genetic blueprint, are formed from extended chromatin fibers as cells enter division remains poorly understood.

As well as solving this long-standing question about one of life’s most fundamental processes, the findings could also lead to insights that advance research on cancer and infertility treatments.

Chromosome structure

Earlier research by Bill Earnshaw and collaborators led to a landmark paper solving a 100-year-old mystery, revealing how long, tangled strands of chromatin are organised into tightly compact chromosomes in dividing cells.

But current low-resolution technologies cannot deliver answers on the process of how chromatin is folded up by molecular machines to form these compact mitotic chromosomes during prophase, the earliest phase of cell division.

During cell division chromosomes are shortened to create structures that are the right size to line-up in the middle of the cell and be partitioned equally between the two daughter cells. 

Bill’s earlier work, with long term US collaborator Job Dekker from the University of Massachusetts, revealed that chromosomes can tightly pack by forming helical coils of nested loops containing smaller loops.

This compaction means the DNA in a mitotic chromosome is roughly 10,000 times shorter than it would normally be if stretched out.

The project will used advanced imaging and genome analysis techniques to generate new insights into chromosomes during the previous mysterious prophase stages as the chromatin compacts. 

Ohad Medalia contributes his expertise in cryo-electron tomography a high-resolution technique that can reveal new insights by tracking thousands of individual chromatin subunits as they are compacted into complex structures suitable for cell division. 

Job Dekker, a professor at the University of Massachusetts and an investigator at the Howard Hughes Medical Institute, will develop new methods to track the action of molecular machines in a genome-wide analysis of the process of loop formation.

Whilst Bill Earnshaw specialises in mitotic chromatin and has developed cell lines with exceptionally accurate cell cycle synchrony – allowing precise step-by-step separation of the various stages of chromatin compaction as cells enter division.

He will also perform the first ever detailed studies of the structure of single chromosomes using tiny "dot" chromosomes from chickens.

The project is set to begin in the spring of 2026 and run for five years, with a potential one-year extension.

About the Funding

ERC Synergy Grants foster collaboration between outstanding researchers, enabling them to combine their expertise, knowledge and resources to push the boundaries of scientific discovery. 

The ERC, set up by the European Union in 2007, is the premier European funding organisation for excellent frontier research.

This funding is part of the EU’s Horizon Europe research and innovation programme. The project was one of 66 projects, to receive a share of €684 million in funding.

It is wonderful to be able to collaborate with friends who happen to be world-leading scientists to gain insights into a process that has fascinated scientists for over 140 years. Our approach, which we call "kinetic sectioning" will enable us to perform a wide range of state-of-the-art studies with minute-by-minute resolution as cells disassemble interphase nuclei and reform the chromatin into compact chromosomes suitable for segregating the genome.

Professor Bill Earnshaw, FRS, FRSE, FMedSci Institute for Cell Biology

Our goal is to uncover the mechanisms underlying mitotic chromosome formation at high resolution, both in cells and in vitro – a task that requires the coordinated implementation of innovative experimental designs across several disciplines. We will combine genome-wide chromatin mapping, super-resolution microscopy and cryo-electron tomography with advanced image analysis and modelling.

Professor Ohad Medalia University of Zurich
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