Prizes for team behind game-changing multi-omics method to decode gene regulation

Key points:

• Institute researchers have developed a new multi-omics method enabling the profiling of multiple histone modifications and gene expression in single cells. The technique provides high sensitivity, making it suitable for use with complex and limited samples, such as embryos and organoids, while also permitting high throughput.
• For this work, lead researcher, Dr Yang Wang received the Institute’s 2025 Sir Michael Berridge Prize, recognising outstanding science.
• The team of Peter Rugg-Gunn and Yang Wang also received the Top Rising Star award by BioCentury Grand Rounds in recognition of the outstanding translational potential of the scMTR-seq method.
• The technique has already been applied by the team to uncover distinct epigenetic patterns in early cell lineages in mouse embryos for the first time.

The Institute team behind the development of a new single-cell multi-omics sequencing method, scMTR-seq, have been recognised by the award of back-to-back prizes. As described in their recent publication, the technique allows the chromatin state of a cell, particularly the combination of histone protein modifications, to be analysed with relevance to gene regulation and appropriate gene expression in cells. Being able to monitor changes in the chromatin state during development or disease is important for understanding underlying mechanisms regulating gene activity.

Dr Yang Wang, a senior research scientist in the Rugg-Gunn lab, was awarded the Institute’s 2025 Sir Michael Berridge Prize for his work, undertaken over a period of nearly five years, on developing the scMTR-seq technique. The prize is awarded annually to a PhD student or postdoc for their contribution to an outstanding piece of science at the Institute. One of the key requirements of this technique was that it could be applied to very limited samples, including embryos.

scMTR-seq, which stands for single-cell multitargets and mRNA sequencing, overcomes several limitations of current methods of detecting chromatin states in cells, being able to profile up to six histone modifications in single cells with high resolution, higher throughput and high cell recovery.

Following the BioCentury Grand Rounds – Europe programme in Cambridge on 17-19^th September, which brought together investors, academic innovators and biopharma leaders, Dr Peter Rugg-Gunn and Yang Wang were jointly awarded the Top Rising Star award in recognition of the outstanding translational potential of scMTR-seq.

Peter, a senior group leader in the Institute’s Epigenetics research programme, outlined the impact of Yang’s work: “Through perseverance, meticulous detail, creative troubleshooting and hard work Yang has succeeded in the formidable task of developing a profiling method that we can apply to small samples and collect data on multiple types of histone modifications as well as the transcriptome. It’s great to see this work enthusiastically received by the scientific community and to see Yang’s contribution recognised with the Berridge Prize and also by the Top Rising Star award by BioCentury Grand Rounds.”

In applying the method, Yang’s research has investigated whether the cell lineages of early-stage mouse embryos possess distinct patterns of histone modifications that may instruct the development and segregation of these lineages. Yang’s method can uniquely address this challenge because of the highly multiplexed information obtained (transcriptome data used to identify cell type, and multiple histone modifications used to collectively infer epigenome patterns). Consequently, the team have shown, for the first time, that the three early embryo lineages have different epigenetic patterns.

Commenting on the awards, Yang said: “I feel honoured and humbled to receive these acknowledgements of the impact of our work. We have invested significant effort into developing and refining this technique and we hope it will be widely adopted and contribute to advancing our understanding of gene regulatory mechanisms across diverse biological systems.

“I am grateful to my colleagues in the Rugg-Gunn lab and to the Genomics facility, Bioinformatics team, and the BSU for their invaluable support in making this work possible.”

Notes

Publication reference: Wang et al. (2025). Combinatorial profiling of multiple histone modifications and transcriptome in single cells using scMTR-seq. Science Advances

Press contact: Dr Louisa Wood, Head of Communications, louisa.wood@babraham.ac.uk

Image description: Dr Yang Wang (left) and Dr Peter Rugg-Gunn (right) shown over a data analysis plot from the scMTR-seq technique (Figure 3, E - Clustered smooth heatmaps showing gene expression and associated histone modification levels at their promoters and gene bodies).

Affiliated authors (in author order):

Yang Wang, senior research scientist, Rugg-Gunn lab

Jingyu Li, former research assistant, Rugg-Gunn/Kelsey labs

Andrew Malcolm, former postdoctoral researcher, Rugg-Gunn lab

William Mansfield, former senior scientific support staff, Biological Support Unit

Stephen Clark, former senior research scientist, Reik lab

Ricard Argelaguet, former postdoctoral researcher, Reik lab

Laura Biggins, Bioinformatician, Bioinformatics group

Richard Acton, Data Outputs Manager, Rugg-Gunn group

Simon Andrews, Head of Bioinformatics

Wolf Reik, Honorary Group Leader

Gavin Kelsey, Head of the Epigenetics research programme

Peter Rugg-Gunn, senior group leader, Epigenetics research programme

Research funding: This research was supported by strategic funding to the Institute from BBSRC and to Peter Rugg-Gunn from the Medical Research Council and Wellcome.

Animal research statement

As a publicly funded research institute, the Babraham Institute is committed to engagement and transparency in all aspects of its research. This research used mice to create embryos, which were analysed by the scMTR-seq technique to look at epigenetic patterning in early development.

All mouse experimentation was approved by the Babraham Institute Animal Welfare and Ethical Review Body. Animal husbandry and experimentation complied with European Union and United Kingdom Home Office legislation.

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