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Adrian Bracken talks about his research into Polycomb group proteins.
Adrian completed his PhD at Trinity College, Dublin in 2000 before undertaking post-doctoral research with Kristian Helin at the European Institute of Oncology in Milan and the University of Copenhagen. Since establishing his own lab in 2008, he has published research on Polycomb proteins in embryonic stem cells, the CHD5 tumor suppressor in neurogenesis, and the non-chromatin role of Polycomb-like 1 in the p53 pathway.
My parents tell me that no matter what they told me as a child, my response was always "why?". So, I guess I was always annoyingly curious about everything! However, it was a summer J1 internship in the lab of Claire Moore at Tufts University, Boston that really opened my eyes to scientific research. This was the spark and I've been hooked ever since.
Our lab studies the PRC2 complex, which is famous for its role in mediating H3K27me3 on chromatin. However, we have discovered two surprising new aspects to PRC2 biology.
Firstly, we have uncovered a chromatin independent role for a PRC2 complex protein called PCL1. So, PCL1 still has a role within the PRC2 complex on chromatin, but we show that it has undergone neofunctionalization (acquiring a new function while maintaining the original) during recent mammalian evolution to allow it to stabilize the p53 tumor suppressor and promote cell cycle arrest or cellular quiescence.
We have another emerging story in which we explore the mechanisms by which PRC2 also mediates the H3K27me2 mark, the much less well-studied, but quantitatively more important product of PRC2 activity.
In the early years it was the fact that my particular gene EZH2, a Polycomb and chromatin repressor, was highly expressed in cancer. I was driven during my post-doctorate in Kristian Helin’s lab to explore both the normal function of EZH2 and to identify its target genes.
In recent years, EZH2, other PRC2 members and indeed even histone H3 have all been found to be mutated in multiple cancer types. This has further fueled my lab’s desire to fully explore the functions of this fascinating PRC2 complex.
Good question! It’s only 5–6 years since we realized the number of chromatin regulators that are mutated in cancer. In Bert Vogelstein’s seminal review in Science in 2013, he highlighted that out of 140 cancer driver genes, 31 encode chromatin regulators, clearly illustrating that a better understanding of their function is a pressing need.
I believe we are in the middle of an explosion of follow up studies in which researchers are modeling these various mutations to both explore the mechanisms by which they drive cancer and towards developing and testing new epigenetic or chromatin-based cancer treatments.
Good first author papers are the ticket to a top class post-doctorate in your dream lab. Therefore, when choosing a lab to do a PhD, make sure to find one in which you believe you can publish good quality first author papers if you work hard. That’s probably the most important advice.
Sometimes it’s good to speak with PhD students already in the lab and ask about the lab works. Remember, Pubmed doesn't lie – it can tell you a lot about the track record of the lab and the PI running it! When you get going, stick at it – it takes persistence and determination to complete a PhD and to get good papers over the line with the reviewers and editors.
Probably another type of scientist to be honest! I think I was always destined to end up doing some form of scientific research.
Inside work, it would be good colleagues who I know and meet regularly at international meetings. It’s always fun catch up with their new results and to share new results from my own lab. For me it’s these scientific discussions with others that make all the hard work worthwhile.
Outside of work, my partner Louise, my family and friends and the big and beautiful Phoenix Park in Dublin to jog around!