Trinity scientists’ cellular identity discovery could impact cancer treatments

7 Apr 2023

Image: © S. Singha/Stock.adobe.com

Trinity scientists have cracked a conundrum surrounding Polycomb protein complex PRC2 which has been puzzling academics for years.

An unprecedented discovery by a team led by Trinity College Dublin (TCD) scientists has resulted in new knowledge of the processes involved in establishing cellular identity.

The team is based at TCD’s School of Genetics and Microbiology. Its findings could have an impact on cancer biology research and cancer treatments.

The scientists’ research focuses on the workings of Polycomb protein complexes, PRC1 and PRC2. A puzzle regarding PRC2 has intrigued scientists in the cellular biology field for years. Two forms (PRC2.1 and PRC2.2) exist in the cell but the TCD team previously showed that the two forms of PRC2 target the same regions of DNA and do the same job. The science community has been questioning why we need two versions of PCR2 ever since.

Now, the team has made a discovery that puts science on the path to answering this question. The team found that PRC2.1 and PRC2.2 recruit different forms of the PRC1 complex to DNA, thereby finally explaining why two versions are needed.

The scientists were not prepared for this result, with some team members believing it was an error.

“This took us by complete surprise. We initially thought there must have been a technical issue with the experiment, but multiple replications confirmed that we had in fact stumbled upon a fascinating new process that reshapes our understanding of the hierarchical workflow of Polycomb complexes,” said Dr Eleanor Glancy.

We were dancing around the lab,” she added, recalling the moment she and her colleagues finally realised what their findings were telling them.

Glancy is a PhD graduate of the TCD Bracken lab – which is named after its leader Prof Adrian Bracken. She spearheaded the research alongside postdoctoral researcher, Dr Cheng Wang. The two scientists received collaborative support from scientists in Italy and the Netherlands. The team published a paper detailing their findings today (7 April) in the journal, Molecular Cell.

The scientists’ work represents a massive contribution to the field of chromatin and epigenetics research. It has further impact in cancer biology research as the genes encoding Polycomb proteins are frequently mutated in cancers.

According to Bracken, his team is currently studying the effects of mutations in childhood brain cancers and adult lymphomas. They are exploring how to target mutations with effective treatments.

“A firm and comprehensive understanding of the workings of these complexes is critical to figuring out new ways to target them in cancer settings. Therefore, this work led by Dr Glancy and Dr Wang in my lab will be built upon here and by other researchers worldwide to advance our approach to many cancers,” he concluded.

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Blathnaid O’Dea was a Careers reporter at Silicon Republic until 2024.

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