Discovery with cancer research impact makes scientists dance in lab

"This work will be built upon here and by other researchers worldwide to advance our approach to figuring out ways to target cancers"
Amal Jos Chacko
Nerve cells attacked by antibodies.jpg
Nerve cells attacked by antibodies. 

Establishing cellular identity has been key to understanding the multitude of different cells in our body and their respective biological duties. A press release issued by scientists from Trinity College Dublin leading a team details an important revelation that has the potential to impact cancer biology and targeted treatments.

Professor Adrian Bracken and his team based in Trinity's School of Genetics and Microbiology studied the workings of Polycomb protein complexes PRC1 and PRC2. Ellen Tuck, a Ph.D. student, analogizes these proteins to “strict librarians” inside cells. “PRC1 and PRC2 block access to certain areas of the genetic library such that a neuron cell won’t have access to muscle genes, and it doesn’t get confused in its cellular identity,” she added.

For years, scientists in this field continued to be intrigued by the existence of two forms- PRC2.1 and PRC2.2- in the cell that were shown to target the same regions of DNA yet did the same job. Why was this so? Surely one version would suffice, right? 

This conundrum has finally been answered. The team found that PRC2.1 and PRC2.2 recruit different forms of the PRC1 complex, explaining the existence of the two versions. 

Discovery with cancer research impact makes scientists dance in lab
An illustration of Polycomb protein complexes critical for maintaining cellular identities

Dr. Eleanor Glancy, a Ph.D. graduate of the Bracken lab, describes the evening when the team finally made sense of the data in front of them. “We initially thought there must have been a technical issue with the experiment, but multiple replications confirmed that we had stumbled upon a fascinating new process that reshapes our understanding of the hierarchical workflow of Polycomb complexes. This took us by complete surprise. We were dancing around the lab,” she recalls. 

The team, spearheaded by Dr. Glancy and Postdoctoral researcher Dr. Cheng Wang in collaboration with scientists in Italy and Netherlands, published their work in the leading journal Molecular Cell.

Their findings are of great relevance to the field of chromatin and epigenetics research and can impact cancer biology research as genes encoding Polycomb proteins are frequently mutated in cancers. 

Professor Bracken and his team worked through the COVID-19 pandemic shutdown keeping up with their tight deadlines and undeterred by failed hypotheses and failed experiments while maintaining social distancing measures to attain this significant breakthrough.

The team currently studies the effects of these mutations in childhood brain cancers and adult lymphomas to gain a better understanding of the biological mechanisms gone rogue, and how they can be targeted to reach more 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,” added Professor Bracken.

Study Abstract

A team of scientists based in Trinity College Dublin talks about their discovery and reasons behind the existence of PRC2.1 and PRC2.2, two Polycomb protein complexes critical to maintaining cellular identity, and their potential impact on cancer treatment research.

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