Unlocking the brain’s building blocks

I’ve always been fascinated by nature and biology and how things work, but my interest in science was ignited by an amazing teacher in year nine in high school, Mr Ryan – no relation. He lit the fuse.

My elder sister lives with epilepsy, so I also grew up having that close connection with a confronting disease. Trying to understand what was happening to her got me very interested in neuroscience.

I wasn’t the best student during my undergraduate degree – I wasn’t particularly engaged in that style of learning, memorising information and attending huge classes, and I was having way too much fun. But just a few weeks before I graduated, I began work on a lab project. It meant sitting there looking at frog eggs that were expressing a transporter protein, which doesn’t sound very exciting. But then I put these electrodes in . . . and I could actually see that an electrical current was being generated, in real time by these little machines that exist in our brain.

It still gives me goosebumps thinking about it. It was so different to the kind of science you do in practicals. This to me was real science: proteins from human brains expressed in a frog egg, generating electricity . . . It amazed me. I was hooked.

What I do is fundamental science. I’m interested in how the proteins in our bodies work at a very basic level. And the proteins I study are found in the brain. I’m interested in what they look like, how they work, and what goes wrong with individual proteins in brain disease.

These proteins are found on the surface of our brain cells, which communicate with each other using chemical messengers or neurotransmitters. The proteins I work on are like mini vacuum cleaners that suck up those neurotransmitters after they’ve done their job, regulating the activity in the brain.

These tiny molecular nano-machines are quite complex in their structure and what they do. And their dysfunction is linked to lots of diseases. They’re also a target of drugs – both therapeutic drugs like antidepressants and antiepileptics, and also drugs of abuse, like cocaine and amphetamine.

We know a lot about how things work, but there’s so much more to learn.

We study these proteins in different systems. First, we purify the native proteins themselves, and use structural biology to try and understand what they look like. One of the newer techniques is cryo-EM, or cryogenic electron microscopy. You have a sample of your purified protein in a buffer, and you literally flash freeze that sample. You then look at their orientations and different confirmations using very high-powered microscopes to solve their structures. That’s one arm of what I do.

We also express these proteins in cells – we actually use those frog eggs – and use a technique called electrophysiology, measuring the electrical current generated by the activity of these transporters.

We know a lot about how things work, but there’s so much more to learn. We still don’t understand how a lot of neurological diseases initiate and progress. They’re very complex.

The next big thing is analysing these proteins in their native environment from a structural biology point of view.

The next big thing is analysing these proteins in their native environment from a structural biology point of view. The technology is coming to enable us to really understand how proteins interact, and how those interactions affect their function. We scientists try to reduce things to their basic components to understand them. But living cells are actually very crowded – there’s lots of different things going on. People are already pulling out huge protein complexes from blood cells, for instance, and solving structures of 10-20 proteins linked together. That’s the next frontier in structural biology.

A lot of the study of brains is obviously post mortem, but imaging technologies are getting better. Hopefully, one day we’ll be imaging things in the human brain while someone’s alive.

The automation of processing and analysis is definitely speeding up research. AI definitely has a role. Potentially there’s a future where there might be a very well-targeted medicine for diseases like Alzheimer’s and epilepsy. It’s conceivable that these pharmacological substances already exist, and we just have to unlock them.

My mentorship work is also really important to me – and gives me great enjoyment. I’m a real people person, which doesn’t always marry with the image of the research scientist as a kind of lone nerd. We aren’t that at all – scientists are very collaborative, and very team-based. And it’s the collaborative side of science which I love.

I collaborate with people in my own university, across Australia, and all over the world. I do whatever I can to support the next generation of researchers, because they need it! This can be a tough job, and feel quite lonely at times.

You shouldn’t have to punch and kick to get to the top.

I had great mentors, so I know what it was like to have a good experience. But I see some of my colleagues didn’t have the same support I did, and that it was much harder for them.

It’s about supporting people on one hand, but it’s also about fixing the system, making it fair, more transparent and more supportive. I don’t think we need to live in this kind of cutthroat competitive environment where only the toughest survive. You shouldn’t have to punch and kick to get to the top, which is a bit how academia has been in the past.

Fortunately, it’s changing. But it will be a great “next big thing” when we can attract and retain the most talented and inspired people into science, no matter their background – and not lose them.

As told to Graem Sims.