Making Milestones: Novel discoveries for the future mind

At 34, Melissa took 6 months off her mining engineering job. She was bored, too young to retire and needed a career change. Now years later, she has successfully submitted her PhD thesis  – an innovative piece of work to underpin the future of Alzheimer’s disease research.

Melissa Eccles is completing a PhD at the Curtin Medical School, co-supervised by Curtin’s Associate Professor Giuseppe Verdile, Dr. Mark Agostino and Associate Professor David Groth. Melissa and Giuseppe reflect on Alzheimer’s disease research, the challenges (and achievements) of pivoting a project and what makes a good scientist.

Melissa:

I started as a mining engineer. I did a Bachelor of Engineering in mining, worked as a mining engineer for 14 years and got bored. I left mining and ended up doing a Bachelor of Science in Molecular Genetics and Biotechnology. I gave myself permission to see where it went and I tried to approach my undergraduate degree with no preconceptions. I didn’t go in with a clear path of what I wanted to do with it, I just wanted to see what opportunities presented themselves. I started on the research path by doing summer research projects, Honours degree and then a PhD.

My PhD focuses on Alzheimer’s disease, specifically looking at two very similar proteins and the influence they have on the pathology of the disease. Beta-amyloid is a protein that is deposited in the brains of people with Alzheimer’s disease. It’s one of the key features of the disease and there are two versions of the enzyme that make beta-amyloid. I’ve been investigating how these enzymes are different and how they contribute to both making and removing beta-amyloid. Ultimately the goal is to have a better understanding of the mechanisms of beta-amyloid generation and removal so we can look for novel ways to target them in Alzheimer’s disease and identify new therapeutics in the future.

It’s a novel area that hasn’t been looked at very much at all, so we needed to start with understanding the mechanisms of the two different types of enzyme, what they’re doing and their contribution to the disease before we can progress towards identifying some specific ways of therapeutically targeting them. My PhD is laying the foundation for a bigger project, so although it is an early stage discovery based project it represents a key step forward.

One of the hardest challenges of the PhD was recognising that the hypothesis we had, for the first 12 months, was no longer valid. We had to pivot the project, which ultimately made it a lot more interesting. While we made some novel discoveries that reshaped the way we looked at the project, I had to deal with that fact that all the work I had been doing on that original hypothesis was now null and void.

I learned that you can’t hold too tightly to your beliefs. As a good scientist, you have to develop the ability to let go. You can’t stake everything on a belief and then blind yourself, bias your interpretation of data and potentially miss out on things. Learning to be vulnerable and be okay with turning around and saying ‘I was wrong and this is why’, that’s probably the biggest challenge but can bring out the most fruitful results.

My greatest achievement? I would say the submission of my thesis. It was nice to be able to see how the pieces came together. At the end of the day, there’s lots of steps along the way but the project itself – the thesis – is the culmination of the project, a combination of the hard work that has been done. Just reading the thesis and being able to say, ‘wow, this is a lot. This is good work. I’m proud of the work that I’ve done.’

Being able to present at an international conference was also special. We went to Sweden to the Alzheimer’s & Parkinson’s Diseases Conference (AD/PD), which is an international Alzheimer’s disease conference and I gave an oral presentation along with a couple of poster presentations. I also recently managed to secure a post-doctoral position at the University of Edinburgh, which is very exciting.

At the end of your PhD, you should be asking more questions than you’ve answered. Otherwise, you’ve not thought about the broader implications of your work. It’s frustrating because you still have to teach yourself and learn how to stay on task and not chase all of the rabbits. But it’s interesting that from a longevity point of view that all the questions will never be answered.

Giuseppe:

I’ve known Melissa for about seven years and first met her through David Groth. At our first meeting I could see the potential that she had as a student. She might not admit it but she’s an organised person, passionate and very motivated, and those are some of the skills you need to do research. She was inquisitive, she wanted to know more and that’s perfect for research.

She has continued a project that I started during my honours way back when. I did bits and pieces as I progressed through my career but Melissa has continued it and expanded it during her PhD. It’s so nice to see something started many years ago come to fruition through Melissa’s PhD.

My supervisory style depends on the student and it also changes as the PhD progresses, a relationship is built. Some students need more supervision than others. Particularly at the start of the project, the supervisor should be there to guide, mentor and support. I try to do that with all my students. Some students need more guidance and support than others. The style of supervision can also change throughout the PhD journey. For both the supervisor and the student, it’s a journey.

And this is what Melissa was talking about; we started with one hypothesis, but through her exploration, it turned around – not completely – but it turned around to another aspect that was fruitful.

By the end of the PhD, students should know much more about the project than the supervisor. They should be informing the supervisor about the knowledge around the project.

About the researchers: