Interviews with Scientists: Dr Samantha Murray
Dr Samantha Murray did her BSc majoring in Neuroscience at Otago University in Dunedin, New Zealand. At the end of her third year, she undertook a summer studentship in a neurodevelopmental lab, and continued on to do her honours project in this lab.
Sam then moved to The University of Auckland to do her PhD at the Centre for Brain Research. Sam completed her PhD last year, during which she studied neuropathology in a large animal model of Huntington’s disease. Sam moved cities after her PhD, and is now working as a Research Assistant studying gene therapy in a large animal model of Batten disease.
It’s great to speak to you, Sam! Firstly, tell us a bit more about your PhD...
My PhD was in biomedical science. In particular I was studying a large animal model of Huntington’s disease. Huntington’s disease is a neurodegenerative disease that is dominantly inherited, meaning each child of a person with Huntington’s disease has a 50% chance of inheriting the disease. The disease is slow-progressing, and causes involuntary movements, psychiatric symptoms (depression, irritability, psychosis), and cognitive symptoms such as deficits in learning, memory, and attention. My lab group primarily worked on post-mortem human brain tissue, so the large animal model was developed by my supervisors and others with the aim of studying the very early stages of the disease, and testing potential therapies in a brain more comparable in size and structure to the human brain. For my PhD I aimed to characterise the neuroanatomy and neurochemistry of specific basal ganglia nuclei that are affected in the human brain in Huntington’s disease, both in control animals and affected animals.
Did you always want to be a scientist when you were younger, and why?
On some level, yes I did. I grew up with my older brother who has a brain injury, as well as my mum working with people with disabilities. Because of this I have always been curious about how the brain works, and what happens when something goes wrong. When I started trying to figure out how to pursue a career in science, my mum said to me that she always knew I would go into a career involving research, as when I was young I used to ask lots of questions, in particular: “Why can’t we fix it?” I got into neurodegenerative diseases in particular because I knew someone with Huntington’s disease when I was younger, and it was horrible to watch someone go through such a slow-progressing and debilitating disease. This is why my focus now is on gene therapy to treat these kinds of diseases.
What advice would you give to someone just starting their PhD?
Research prospective supervisors before you decide on a lab – the project is an important part of it but so is having a supportive, available supervisor. Talk to current lab members about their experiences and the work they do.
Read, read, read! Get familiar with your topic, as well as the techniques you plan to use, so that you can design your experiments appropriately.
Keep a tidy lab book! This will be so important when you come to writing your thesis. Along with this, keep thorough records of each experiment: what you did, and why, and most importantly the result! Three or four years on you will have forgotten why you changed that buffer, or that incubation time.
Don’t underestimate the power of networking – work on your networking skills early.
Take rests and look after yourself.
What did you enjoy most about your PhD?
I really enjoyed the community engagement aspect of my PhD. My lab group was hugely involved in the Huntington’s disease community, not only the wider research community, but engagement with patients, their families and caregivers, and clinicians. It really kept me motivated, when times were hard in the lab, I had the patients and families in my mind, always so enthusiastic and supportive of our research. I also enjoyed the opportunity I had to work as a teaching assistant in undergraduate labs. My favourite lab to assist in was the brain dissection lab for the medical students, taught by my supervisor – it never got old seeing the awe on the faces of the students as they comprehended the complexity of the structure of the human brain.
Tell us a bit more about what you’re working on at the moment...
I am currently working as a research assistant, hoping to eventually get funding to work as a postdoc. I am working on a large animal model of Batten disease. Batten disease, also known as neuronal ceroid lipofuscinoses (NCL), is an inherited neurodegenerative disorder that primarily affects infants and children. It is inherited in an autosomal recessive manner, meaning that the child has to have two defective copies of the gene; one defective gene from each parent. People with one defective gene are known as carriers, and will not develop the disease. Children with Batten disease suffer from seizures and lose their sight. Their brains progressively shrink in size as neurons are lost, primarily from the visual cortex and parieto-occipital cortex. Neurons accumulate ‘storage material’ in lysosomes that primarily consists of subunit C of mitochondrial ATP synthase. There are several different variants of the disease, classified by age at onset (infantile, late-infantile, juvenile, adult), and 13 different genes, which contain a variety of mutations, associated with Batten disease (CLN1-8, and CLN10-14). Our group is trialling gene therapy in our model to try to replace the gene which is defective, with the hope that introducing the properly functioning gene will delay or stop the onset of disease in pre-symptomatic subjects, and halt or reverse the disease process in symptomatic subjects.
What does a typical day in the lab look like for you?
Every day is different! Some days I spend in the lab, cutting brain tissue or sometimes peripheral tissues, into very thin slices using a microtome. I then use these sections of tissue for my immunohistochemistry experiments to visualise particular proteins of interest in the tissue. Some days I will be at the microscope. Some days I will be at my desk analysing ERG (electroretinogram) data to track the response of the cells of the retina over time in treated and untreated animals, or analysing CT (computed tomography) scans to measure intracranial volume of animals over time. A few days a month I will spend in the field with the animals, taking blood samples for genotyping, or performing CT scans or ERGs. And of course writing papers and grants, and attending seminars.
If you weren’t a scientist, what do you think you’d be doing?
I am a total animal lover, so when I was younger I always wanted to be a vet. But now with the rise in popularity of ‘doggy day care’ and cat cafes, I would probably run one of those!
Outside the lab, what do you enjoy doing?
Reading, walking, yoga, science communication, spending time with friends and family.
What is it about your field of research that gets you most excited?
The promise of gene therapy for inherited brain diseases. Gene silencing therapy refers to treatment whereby we can ‘switch off’ a gene that has a gain of function mutation, meaning the mutation in the gene causes it to take on a new, harmful, function. We can silence the gene by creating a complementary RNA strand to the target mRNA, which will bind to the target mRNA and either cleave/degrade the target mRNA or block its translation. Conversely, gene therapy can be used to replace genes which have a loss of function mutation. This is what we are trying to do with trials of gene therapy for Batten disease in our animal model. Studies from animal models of various neurodegenerative diseases have shown that gene silencing or gene replacement therapy can delay or stop onset of disease, and in some cases ‘reverse’ the disease process.
What do you think are the biggest challenges currently facing life scientists and their work?
I think the biggest challenge facing scientists today is funding. Specifically for early career researchers I think the emphasis put on number and impact factor of publications is a challenge, as well as gender bias with so many top positions being held by males – although I would like to think change is in the air on that one.
Which scientists working today do you most admire, and why?
Would it be a cliché to say my supervisor? My current supervisor and mentor is an early career researcher herself, who worked as a technician for many years before deciding to do a PhD (with two young kids!) Her PhD was amazing, and according to her supervisor is the best thesis he has had in his time as a PI (and he’s 70 so that’s saying something!) She is an extremely hard worker, very focussed and motivated, which has been a good influence on me. As a mentor she is not only a great teacher but very kind and caring, and is always available to answer any questions I have or just chat science.
What’s your favourite science joke?
A science pick-up line: “If I had to choose between DNA and RNA, I would choose RNA because it has U in it.”
What's your favourite science quote?
“All outstanding work, in art as well as in science, results from immense zeal applied to a great idea.”
― Santiago Ramón y Cajal, Advice for a Young Investigator
What do you think is the greatest scientific discovery of all time?The discovery of DNA. Understanding the basis of an animal’s genome and how DNA encodes proteins is crucial to further understanding what goes wrong in disease and how to potentially fix it. That circles back to what I say talking about earlier regarding gene therapy – without understanding the makeup of DNA we would never be able to target harmful genes in that way, let alone know what the harmful genes are!
Thank you for a fascinating interview, Sam! We wish you the very best of luck with your research.
You can also connect with Sam on LinkedIn here