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Researcher Spotlight: Dr Nichola Lax

28 Jul, 2014

With mitochondrial replacement therapy in the news at the moment, following a positive government response to the public consultation on the technique, we thought it would be good to talk to someone who works with faulty mitochondria. Dr Nichola Lax is a research associate working in the Wellcome Trust Centre for Mitochondrial Research at Newcastle University, and she shares her hopes about her research with us…

Dr Nichola Lax, Newcastle

What are you working on?

I’m working on a project that aims to understand how genetic defects (or mutations) in mitochondrial DNA cause mitochondrial dysfunction in neurons, leading to epilepsy.

Mitochondrial disease can have a variety of different symptoms because mitochondria are present in all our cells (apart from red blood cells). This means patients may have problems with their vision, muscle weakness, and neurological disorders. It is the neurological disorders that are most prominent in these patients and can also be most devastating, so I am interested in learning more about these so that we might be able to offer more effective treatments.

Epilepsy is very common in patients with mitochondrial disease and is a pathological condition where groups of neurons suddenly become intensely electrically active and fire information rapidly resulting in a seizure.

Our understanding about how the pathological processes begin and progress in patients with epilepsy is still limited and so the focus of my work is to address this problem. I use post mortem human brain tissues to investigate which neurons are most vulnerable to mitochondrial DNA mutations and try to understand how epilepsy develops in these patients.

What does your average day involve?

A typical day begins with my morning walk across the Town Moor to the Medical School, attempting to negotiate my way through the resident cows.

The first thing I do when I reach the lab is make a cup of coffee, check my emails and then power up my favourite microscope. For my work, I tend to use a variety of different microscopy techniques to look at neurons, but with this particular microscope I feel I have truly bonded. This one can only be described as the ultimate microscope, the Nikon A1R, it’s very fancy (expensive!) and it almost feels like I’m operating a spaceship when I’m using it!

It’s a confocal microscope, located in what affectionately call “the dungeon” downstairs, and this piece of equipment lets me photograph beautiful multi-coloured images of mitochondria inside a variety of different cell types in very thin sections of human brain.

This microscope has allowed me to look at proteins expressed inside the mitochondria to precisely establish how dysfunctional these mitochondria are within specific cell types, so for instance, in a typical experiment I label my mitochondria with a pink fluorescent tag, a protein called complex I with a red fluorescent tag and complex IV with a green tag and a marker for neurons with a blue tag. I can then photograph them and see whether all colours are located in the same spot and if any are missing, find out which ones – typically complexes I and IV are lost in neurons from patients. I want to understand the consequence of this.

Once I have my images, I go back upstairs to the lab – generally feeling a bit like a mole, and catch up with my colleagues and see if there any cake on offer in the tea room (our lab is full of incredible bakers).

I currently supervise three PhD students in our lab who have a shared interest in understanding the contribution of mitochondrial dysfunction in neurodegeneration in patients and so I would meet with them and find out how their research projects are progressing, talk about results and any issues they might be having. This is often hugely constructive as it allows us to discuss new ideas, focus our research questions and think about the broader picture of our research.

The Nikon A1R and a multicoloured neuron.

The Nikon A1R and a multicoloured neuron.

The remainder of the day, I perform image analysis (see how many pink, red and green spots are present within blue cells) and then take the numbers from this to try to interpret what is happening to these cells. If there is less red and green within the pink spots then this tells me that the machinery important for energy generation is missing and therefore these cells are what we call respiratory chain deficient. I want to understand how they become deficient and what it means for that particular cell. If it’s ‘Fridge Friday’, the day ends with pizza and beer with everyone from the group where we can have a chat about science or life in general.

Why is your work important?

So many patients with mitochondrial disease are affected by neurological impairments and this can have a huge effect on their quality of life and the degree to which they are disabled.

Epilepsy affects approximately one third of patients with mitochondrial disease, and currently treatment is limited, and prognosis may be poor for these individuals. It is enormously important that my work tries to understand why these patients get epilepsy and addresses the specific neural mechanisms that might help us devise new treatment strategies to prevent epilepsy.

This type of research also has important implications for other neurodegenerative disorders where mitochondrial dysfunction may play a role, such as in Parkinson’s disease.

What do you hope the impact of your work will be?

I really hope that my research will help increase our knowledge about mitochondrial function and dysfunction in the brain, and help us to devise better treatment strategies for patients so that we might be able to improve their quality of life.

How did you come to be working on this topic/in this field?

Brain cake (doesn't actually contain brains)

Brain shaped cake in our tea-room

I’ve been really interested in science from an early age, and I knew when I was studying for my A-levels that I wanted to pursue Science to a higher level.

I applied for the biomedical sciences degree at Newcastle University because it was at that point I knew I wanted to work in research, but I still wasn’t particularly sure which aspect. It became clear to me that neuroscience was an area that really appealed to me and was something I wanted to learn more about.

I did an undergraduate research project looking at dopamine receptor changes in the brain following nicotine addiction, and then went on to study an MRes in neuroscience where I investigated the molecular basis for visual hallucination in dementia with Lewy bodies. After my MRes, I had an interview for a PhD project investigating the neurodegenerative features in patients with mitochondrial disease and this is something that remains my major interest today.

How has Wellcome funding helped you/your research/your career?

Wellcome Trust funding has really allowed me to work on something that I feel very passionate about and allowed me to professionally develop from PhD student to post doc. This funding has enabled me to further my research studies at the bench to look at specific mechanisms of disease by giving me an opportunity to test new techniques and answer more ambitious scientific questions.

What’s the most frequently asked question about your work?

It depends on who is asking! People from the scientific community tend to ask me why certain parts of the brain are more vulnerable to mitochondrial dysfunction? Which is something I’m still trying to answer.

School children will ask me what the brain feels like? This is more straightforward and I can usually offer them an agarose jelly brain to feel.

Tell us something about you that might surprise us…

I have recently become a lot more active, bought a bike and starting running, in fact I am running the Great North Run half marathon for the Lily Foundation, a charity which supports families with mitochondrial disease, raises awareness of these disorders and also funds research.

What keeps you awake at night?

Usually I don’t have too many issues falling asleep at night, however that may have something to do with the wafer-thin curtains we bought when we moved into our house three months ago which means the sun wakes me up at 5am each day! If I have spent a lot of time of the Nikon A1R that day, I do have a tendency to dream about counting multicoloured neurons!

What’s the best piece of advice you’ve been given?

My supervisor always tells me that whenever I give a talk I should make sure it tells an interesting story!

The chain reaction question, posed by the previous spotlight participant, Dr Margaret Robinson, is this: What were your best and worst moments in science?

Best – As part of my work, I get travel to scientific conferences where many experts in my research field will meet to talk about the latest and greatest scientific research going on across the globe. This gives me an exciting opportunity to talk about my work, learn more about mitochondria, collaborate with people in different parts of the world and also see a bit more of the world!

Worst – When a seemingly straightforward experiment fails repeatedly (despite working well last week!) without any logical explanation. Fortunately, most of the time, these unlucky spells don’t last too long!

You can find out more about Nichola’s work and the Wellcome Trust Centre for Mitochondrial Research on their pages of the University of Newcastle website. Her most recent papers include Quantitative quadruple-label immunofluorescence of mitochondrial and cytoplasmic proteins in single neurons from human midbrain tissue and Early-onset cataracts, spastic paraparesis, and ataxia caused by a novel mitochondrial tRNAGlu (MT-TE) gene mutation causing severe complex I deficiency: a clinical, molecular, and neuropathologic study.

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