How a PhD led to an epilepsy clinical trial – and a new career

 

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After six years in the lab, Dr Umesh Nair wanted to explore his interest in business as well as neuroscience. He now works as a product manager for a scientific equipment company. The knowledge he gained through his PhD has proved invaluable, as he now helps researchers meet their own infrastructure needs.

Life after graduate research: Dr Umesh Nair

In what area of research was your PhD?

Neuroscience, specifically childhood epilepsy.

What were you trying to discover in your PhD research?

I explored two types of childhood epilepsy, both linked to mutations in the KCNT1 gene. This gene is involved in making channels for transporting potassium ions into and out of cells, which is necessary for cells to transmit electrical signals. I also investigated new treatments for these conditions.

In my honours research, I’d concluded that there is a relationship between mutations in the KCNT1 gene and these two types of childhood epilepsy. But during my PhD, I investigated many more KCNT1 mutations and realised that the relationship wasn’t as straightforward as I’d thought – patients with the same mutation could have very different symptoms. Understanding this was the first part of my PhD journey.

In my honours project, I had showed that a drug called quinidine could reduce the effects of different KCNT1 mutations in cells grown in the lab. Quinidine was originally created to treat heart arrhythmia, but it has characteristics that could help to treat these particular forms of epilepsy in the clinic. So in the second part of my PhD project, I embarked on a process of repurposing the drug.

Why did you decide to do a PhD?

I’d always been interested in neuroscience, and I was really captivated by neurophysiology in my undergraduate degree. I was intrigued by how ion channels affect neuron signalling in the brain, and I wanted to study that closely. I had an interview with Professor Steven Petrou and Associate Professor Chris Reid and I did my honours project with them at the Florey Institute.

I was able to publish my honours work, which gave me the motivation to continue my research with a PhD. I felt that with more time I could discover more.

What were the main findings of your PhD research?

In certain epilepsies, potassium channels do not work properly. They are more active than normal, which affects the cells’ electrical signals and causes the brain to become overexcited, resulting in seizures. Quinidine is a channel blocker – it lodges itself in ion channels and makes it more difficult for ions to pass through. During my PhD, I discovered that certain concentrations of quinidine reduce the activity of the potassium channels in cells with KCNT1 mutations. It was therefore a starting point for a therapy.

One of the main outcomes of my research was the optimisation of an assay that tests the effects of drugs on mutated genes. This method is now available as a framework for other researchers to use.

Based in part on research that I had done at the Florey Institute, our collaborators at the Austin Hospital launched a clinical trial to test quinidine on adults and teenagers with KCNT1-related epilepsy. I never expected that the topic of my research would end up in a clinical trial, but it did – and I was thrilled. Unfortunately, the trial showed that the drug didn’t work on the age group tested. However, since then, researchers worldwide have tested quinidine on younger patients with more severe KCNT1-related epilepsy. The drug has reduced the number of seizures in patients with some, but not all, KCNT1 mutations. Fewer seizures has been linked to longer life and higher IQ.

Even though I wasn’t directly involved in the clinical trials, I’m happy to have made a contribution to research that could change people’s lives.

The focus now is on reducing the drug’s side effects and identifying which particular KCNT1 mutations – and therefore which patients – it can treat. So, there’s still a lot of work to be done before quinidine can be prescribed to treat these two forms of epilepsy.

Why did you choose to do your PhD at the University of Melbourne?

The University is ranked as the number one university in Australia, and that was certainly appealing. But the main reason was because I was going to be working with world-renowned researchers. And I would have access to the latest technology.

My PhD supervisors, Professor Petrou and Dr Snezana Maljevic, are leading scientists in ion channel research. And they have established labs with a good number of post-docs. Although not your supervisors, post-docs become your confidantes and help to give you the required motivation and push to keep going.

Also, the lab I worked in was brand new. A comfortable and inspiring lab was one of my most important criteria, because I knew I’d potentially be spending a lot of time there!

I also gained two important scholarships from the University – one covering the cost of the PhD and one for living expenses. It’s not easy to obtain these and I was very grateful.

What was the best part about your research?

Working with world-renowned researchers and having access to technology that helped me be more productive. For example, the lab has a piece of German machinery called a Robocyte, which enabled me to take the measurements I needed in a matter of hours rather than the days it would’ve taken to do manually. I could get results quickly and economically without going through too much fuss, which in turn meant that I could make more progress with my research.

I also received two awards from the Florey Institute for my presentations at the annual student talks. I used this money and other funding for travelling to conferences and lab visits. Networking was really important for my research: one of my collaborators was someone I met at a conference.

How has your PhD shaped your current work situation?

I’m no longer a researcher, but still very much interested and involved in research. After six years of being in a lab, I needed to go out and explore. Professor Petrou was very supportive of my move and has encouraged me to return to research whenever I want.

I’d always had an interest in business, and now I’m combining this with life sciences. I work for a scientific equipment company as one of their product managers. I manage the proteomics, biobanking and stem cells products, which include products that I came across in my PhD.

I travel around Australia and New Zealand to meet clients and explain how our products can solve their research challenges. The knowledge I gained during my research has made it possible for me to market and to talk confidently about the products.

I’ve been at the company for two and a half years and have carved my own path. I love my role. It’s different than research but it’s exciting.

First published on 20 March 2024.


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