Star Scientist of the Month -Dr Eddie Ip

Despite being busy managing a quickly expanding lab, Eleni has always given consistent contributions into my PhD, which was amazing. I couldn’t have done it without her.

As well as Eleni, my co-supervisor was Professor Sally Dunwoodie, head of the Embryology lab at the Victor Chang Cardiac Research Institute. My PhD was very much collaborative between the two labs.

What was your PhD focused on?

The PhD itself looked at the patient cohort for congenital heart disease that Sally has gathered, along with Dr David Winlaw and Westmead Children’s hospital. Using bioinformatic software and techniques, we were trying to find variants that may be the cause behind the congenital heart disease in those patients.

Previously, the analysis was usually family by family, studying each family members genome sequence to understand where the congenital heart disease may have come from. This is a very time-consuming process.

However, now Sally has been able to get whole genome sequencing applied to the large cohort of patients, I think in total more than a hundred families, which is incredible. We want to be able to look at all that data, across the board, in a much speedier fashion by prioritising the pathogenicity, or the severity in causing disease to the patient of the genetic variants. This will hopefully help us narrow down the gene(s) that can be attributed to the condition.

Another part of my PhD involved investigating how to find the ‘unknown’ genes leading to congenital heart disease (CHD). I was looking for genes in the CHD patients that have more variants in them compared to control samples, than those seen in healthy patients. If a gene has more damaging variants compared to healthy people, it might be a gene that’s causing CHD. That’s the area of focus I am really interested in continuing, looking at the genes we haven’t looked at before and don’t understand as much about.

Were you successful in doing that?

Yes, we had some success, using our method against the genes curated by Sally’s lab, we were able to improve the diagnostic rate for congenital heart disease from a generally accepted 20% to 30%. Those results were published in a paper authored by Dimuthu Alankarage, a postdoc in Sally’s lab. When we looked at this large cohort of patients, we achieved at least 30% diagnosis for the cause of congenital heart disease in those families.

That’s a great result! So, tell us more about the tool you developed to be able to achieve that?

My tool is called VPOT, it is a variant prioritisation software. So far it has mostly been used within the Victor Chang Cardiac Research Institute, but it is freely available to the public. It was published in the journal Genomics Proteomics and Bioinformatics.

I combined ‘predictive’ algorithm scores for each variant with filtering criteria to create a single priority score that allows the user, the person searching through those variants, to isolate or prioritise variants that are more likely to be damaging.

Each genome has at least a million different variants, this tool allows us to sort through them, to find out which ones are most damaging or more likely to cause a disease. Doing that manually takes a lot of time. By utilising VPOT, not only can we look at these millions of variants, but we can also look at hundreds of patients at the same time. It saves a substantial amount of time.

It’s great to see my tool being used in the Institute at the moment. Not just in Sally’s lab but also in Professor Diane Fatkin’s Inherited Diseases lab. I believe Professor Bob Graham’s SCAD lab is also about to start using it as well.

What were you doing before your PhD?

I guess I am a little different to other PhD students because I’m a mature student. Prior to my studies, I worked as an IT consultant, mostly in the airline industry. I was lucky enough to spend several years overseas, mostly in America and the UK. I finished up in New York, with Citibank.

I returned to studying because I wanted to do more with my life. The IT work was interesting, but it wasn’t fulfilling for me. I think the work I am involved in now is so much more rewarding. It’s not just looking at numbers for the sake of numbers, it’s looking at them for the sake of helping people.

Do you have any tips for students choosing their PhD projects?

At the beginning of your PhD, you’re really looking for guidance from your supervisor and from my point of view, because I was working on an established project with the Embryology lab, that gave me a lot of focus. I think having a clear focus is absolutely vital.

The important thing is, apart from doing the things that are asked of you, you also want to think about and explore things that you come across as you’re doing your normal tasks.

For me, while I was analysing the congenital heart disease data from the cohort of patients, I realised there was a gap in the analysis process. That’s where I came up with the idea for VPOT, the tool I created.

So, I would say my tip for when you’re starting out is keep doing your assigned work, but in the back of your mind, think about how you could branch out and create your own project? Look for potential gaps and how things could be improved so you can drive something new for yourself.

Do you have any tips for choosing the right PhD supervisor?

I think the most important component of your PhD is your supervisor, without them you will get nothing done. Without the support of your supervisor, you won’t achieve your end goal because it will just be too hard a slog.

I would highly recommend doing a summer project first. I completed a summer project and my honours with Professor Sally Dunwoodie and she then recommended I continue on to do a PhD. My experience in the lab during that time helped me see what I was really interested in and because I had that initial contact at the Institute already, I was able to get in touch with the right people and the right laboratory easily.

You should definitely be looking for a supervisor that is involved in projects you are interested in. Look at their previous body of work and think about if their work will stimulate you to do your PhD and come up with something new. A PhD is supposed to be a new contribution to the scientific community, so try and keep that in the forefront of your mind, will this supervisor inspire you to make that contribution?

Do you feel that’s something you were able to achieve?

Yes, I definitely think so. I think the tools I developed and helping with the analysis is essentially moving the diagnosis of Congenital heart disease forward. That’s a great contribution to be part of. The work done by Sally and Eleni is amazing. Congenital heart disease is the leading childhood disease in the world, so it’s important to improve the understanding of the disease.

During your PhD, did you have any moments where you felt like you weren’t sure where to go next? And if so, what did you do to get through that?

Oh yes, definitely!

When you first start your PhD, you’re so excited about the work you’re doing because it’s all new. It moves so fast and you can just ride along on that flow but towards the end, as you’re getting closer and closer to the finish line, it becomes more testing because you know you need to get your project done. You start to worry and question if you have done enough to get it over the line. I really felt the strain towards the end, especially once I started writing, because I found it so much more isolating, you aren’t interacting with the rest of the lab as much as you were before.

The way I got through it, was by talking to my supervisor. Eleni always gave me such great feedback and kept my morale high.

Also, speak to your lab members to combat the isolation of writing.

I think another good thing to do is to take a step back and take some time out, away from what you’re doing. Give yourself some breathing room. It takes such a long time to write the thesis, so I would take moments for myself to get settled and feel calmer and then attack it again. When I took the time to step back, I found it helped me see the bigger picture of the whole process, it helped me think “Yeah this is worthwhile, I’m getting close and I’m going to finish this.”

How did you switch off when you needed to take a break from your PhD?

I really like to be outside. I play golf and tennis is a big passion of mine. I actually got into tennis umpiring about six years ago, I really wanted to contribute something back to tennis, as it’s a sport I love so much. I’ve been down to the Australian Open in Melbourne for the past three years working as a lines person. I was lucky enough to work all the way through to the semi-finals last year. I have been fortunate to have the opportunity to umpire matches with Djokovic, Nadal, Barty and Roger Federer (pictured below with Eddie umpiring in the background).

I remember I was umpiring the final at the ATP cup last year - Nadal and Djokovic were playing. I was on the centre line and Nadal is serving and I swear, the ball touches the line, so I made the safe call. Djokovic turns and gives me a look and he challenges. Using hawk eye, they were zooming in on the line and finally it showed a sliver of a gap between the ball and the line. I'd made the wrong call! To make it worse two games later the exact same thing happened again, and Djokovic turns to me and just stared at me. That was definitely an experience to have Djokovic eyeball me! Those kinds of matches are some fantastic highlights I never would have imagined I would have experienced.

How fantastic! Do you have any words of advice for prospective PhD students?

Don’t dwell on the mistakes you make along the way. You have to just keep going onto the next part of work. You have to keep looking forward at how you can improve.