Rad21 is part of the cohesin complex. The whole idea of cohesin as a transcriptional regulator was virtually unheard of when I found the gene in 2005, so the effect on runx1 expression was confusing. In fact, it is only slightly less confusing today, which is why my lab is still researching how Runx1 and other genes are regulated by cohesin. So, thanks to forward genetics, I got to be among the earliest researchers on cohesin and gene regulation. It wasn’t until several years later that cohesin mutations were found in multiple cancers by genome sequencing.

In your career to date, of what are you most proud?

Hanging in there for the last couple of years of my project in Auckland to successfully identify the affected gene in my zebrafish mutant. In those days, mutations from zebrafish screens had to be positionally cloned by relentless, tedious mapping with polymorphisms. It took me a couple of years to do the screen, and then at least 2 years of positional cloning (along with having 2 kids during that time). I was even advised at one point to give up on the mutant because it looked pretty dead (and therefore not interesting)! But it was actually the way that it died that gave me a clue as to what gene was affected. Previously working on the cell cycle helped me recognise that mutant embryos died with cells arrested in G2/M. This implicated Rad21, which is essential for mitosis. It was a tough time career-wise; I had gone 5 years without a paper and then it took several attempts to get the resulting paper on Rad21 published. I’m proud of that work, which is quite highly cited now, and of surviving that time long enough to start my own group.  

Can you tell us about a something happening in your lab right now that you’re excited about working on?

One view is that cohesin’s developmental role involves regulation of gene expression alone, distinct from its role in cell division. I’m excited by the idea that cohesin functions at the nexus of both cell cycle regulation and gene expression to influence the outcome of developmental signalling pathways. In the lab right now, we are using stem cells in the zebrafish embryo tailbud to dissect the cell cycle role from the transcriptional role of cohesin in developmental biology. We’re also looking at the interaction of cohesin mutations with developmental signalling pathways in IPSCs and zebrafish. I’m excited to apply single cell sequencing technologies to get a handle on these questions.

Would you like to tell us a little about the University of Otago?

The University of Otago is at the heart of Dunedin city in Te Wai Pounamu (South Island), a wild and beautiful spot. The best thing about the University is its inspirational and collegial community. We have possibly the largest and most diverse collection of genetics researchers in Australasia, represented by our Genetics Otago Research Centre (see @GeneticsOtago). There’s never a shortage of people to have coffee with and bounce around ideas. 

If funding and time were unlimited, what dream idea or project would you like to develop? 

I do have this long-standing problem that my ideas are too already big for my budgets! If I had truly unlimited funds, I would set up a comprehensive high throughput sequencing Core Facility for the University of Otago, complete with 10x Genomics. Ideally, I would hand them some cells and they would give me back data a week later. We have developed a few zebrafish cohesin mutants that I’d like to analyse across several stages of development, singly and in combination, in different stem cell populations.

Outside your own lab, what research or technological developments in the field are you excited about?

I am of course a massive fan of the big sequencing studies that identified genome structure and the mechanisms (such as loop extrusion) that organise the nucleus. The next challenges will be to understand how genome organising factors interact with cell metabolism and signalling pathways to regulate cell state. I’m fascinated by some recent papers from the Pourquié and Burgess labs showing that glycolysis influences how developmental signals are interpreted. How does this connect back to the genome?

How important has collaboration been to your research and your career?

Collaboration has been crucial. I’ve been lucky to have some wonderful colleagues in NZ to work with, but I have also had some great experiences collaborating with international scientists in the field. I don’t think my career would have gone very far without these interactions.

Can you give us any advice for early career biomedical researchers?

Times have never been more challenging for ECRs than they are now. It’s hard to give meaningful career advice because strategies that worked for me and my contemporaries might not work for ECRs today. Even today though, I would say to an ECR that you should back yourself and your ideas – you never know if today’s strange inexplicable result in the lab might not turn out to be hugely significant in the future. Tenacity (i.e., stubbornness) is also a pretty universal attribute for success in biomedical research. Don’t be afraid to reach out and form your own networks, as these could be crucial for future opportunities. And it really helps if you enjoy what you do!

Outside of work, what do you like to do?

I like mucking around on bikes, and have done all sorts of different types of cycling over the years. The Dunedin area has interesting, if hilly, riding territory. There are some great mountain biking trails, and possibly the best views you’ll ever experience on a road ride. I also like the odd spot of gardening, and of course, chilling with my family.