Behind the research: A new principle for phosphatase substrate recognition

We caught up with three of the paper's first authors, Tomoaki, Gege and Josip, to find out more about the research, the challenges along the way and their experiences of working in the Barr Lab.

From left: Josip, Gege and Tomoaki

Tomoaki: Understanding the mechanisms of cell division

How long have you been in the Barr Lab?

It's been eight years since I joined the Barr Lab in November 2018.

Can you tell us a little about your latest paper and why the findings are important?

Our research focuses on Aurora A, a protein kinase that plays a crucial role in cell division, and protein phosphatase 6 (PP6), which counteracts its activity. Changes to both Aurora A and PP6 are important in human cancers, so we wanted to better understand how they work together.

Until now, it wasn't clear how PP6 recognises its targets. We discovered that different forms of PP6 have distinct roles in regulating Aurora A, and that another kinase, PLK1, can control this process during cell division.

Importantly, we identified a new mechanism by which PP6 recognises Aurora A, providing fresh insights into how these proteins work together to regulate cell division.

What's the best thing about working in the Barr Lab?

One of the best things about working in the Barr Lab is that you can test ideas in multiple ways, such as through biochemistry, cell biology and structural biology. This allows us to pursue projects with convincing data – it's one of our main strengths and I believe it sets our lab apart from many others.

Josip: A research journey spanning more than a decade

How long were you in the Barr Lab?

For my DPhil, four years plus changes.

This has been a particularly long-running project. Can you tell us how it developed and what it took to get the paper published?

This ended up being an exceptionally long-running project, which I started in 2014.

By the end of my DPhil in 2018/2019, we could show which PP6 subunits target Aurora A, and that their activity can be regulated by PLK1. However, we couldn't clearly demonstrate the mechanisms underlying substrate recognition and activity regulation.

It took years of additional work by Gege and later Tomoaki to nail this down. The study in its finished form is extremely exhaustive, and I think this is a testament to both the difficulty of the project and the tenacity and hard work they put in to round it off.

What did you value most about working in the Barr Lab?

I think the Barr group's main strength is its scientific rigour, insistence on quality, and chasing truth rather than trends.

For me as a DPhil student, this meant having a very thorough learning experience, which prepared me to pursue future projects confidently and saved me from falling into artifact traps in subsequent projects.

Another highlight worth mentioning is writing – Francis is exceptionally good at scientific writing and puts in the effort to pass this skill on.

What's next for you?

Having continued in research since completing my DPhil some years ago, I would very much like to establish my own research programme as a group leader at a university or research institute.

Gege: Putting the pieces together

How long were you in the Barr Lab?

I was in the Barr Lab from September 2021 to September 2025, so four years.

What did you particularly enjoy about working on this project?

This paper was built on Josip's PhD work and became the major project during my postdoc.

One aspect I particularly enjoyed was systematically designing and testing different protein variants. It sometimes felt a bit like playing with LEGO – trying different combinations, seeing how they worked, and gradually building a clearer picture of the underlying mechanisms.

Of course, this also required a lot of persistence and resilience, as not every experiment worked as expected.

What's the most important thing you learned from the research?

One important lesson was to be careful when interpreting experimental observations and to constantly challenge my own hypotheses from different perspectives.

For example, a loss of detectable interaction between two proteins does not necessarily mean that their functional relationship or activity is also lost.

This reminded me how important it is not to jump to conclusions based on a single observation, but to consider different possibilities and interpret findings in a broader context.

Spanning more than a decade, the study reflects the persistence, collaboration and scientific rigour involved in uncovering the molecular mechanisms that regulate cell division.

Read the paper: A new principle for phosphatase substrate recognition – The EMBO Journal