Interviews with Scientists: James Quinn
In our next Interviews with Scientists, meet James Quinn! James is a final year PhD student studying the proteolytic cleavage of tau in different types of dementia at the University of Manchester in The Hooper Lab.
When he’s not in the lab, you’ll find James out and about doing public engagement, running, going to the gym or seeing live bands and DJ sets.
Thanks for speaking to us James! Firstly tell us more about your PhD...
My PhD research has focused on the proteolysis of the microtubule-associated protein tau in dementia pathogenesis. This is important because current predictions show that 131.5 million people worldwide will be living with dementia by 2050. We urgently need to understand the molecular mechanisms underpinning disease to help in the hunt for therapeutics and for disease-detecting biomarkers. Tau metabolism is altered in different dementias, the so-called tauopathies. During tauopathy progression, tau detaches from microtubules, aggregates into oligomers and neurofibrillary tangles, which can be secreted from neurons, and spread through the brain, something which is exacerbated through post-translational modifications such as proteolysis by a range of different proteases. Recent work has shown that proteolytic fragments of tau have neurotoxic properties, an increased propensity to be phosphorylated and aggregate into neurofibrillary tangles. My research so far has identified granzyme A as a novel protease of tau through bioinformatics analysis. I have characterised granzyme A-cleavage of tau using recombinant assays and cell transfections, determining the cleavage sites with mass spectrometry and confirming the cleavage sites through site-directed mutagenesis to inhibit proteolytic cleavage. My work is now determining the cellular effects of these granzyme A-cleaved tau fragments. Alongside this, I am investigating the presence of both granzyme A and granzyme A-cleaved tau fragments in the brains of patients with specific forms of dementia. My other research topic focuses on looking at global proteomic changes in plasma from patients with Alzheimer’s disease compared to healthy aged controls in order to find plasma biomarkers that can be used to track disease progression, predict disease onset and differentiate between different types of dementia.
Did you always want to be a scientist when you were younger, and why?
I never actually wanted to be a scientist when I was growing up. I always loved helping and explaining things to others so I thought I would go into teaching. When I was at school I was more interested in playing online PC games and making videos of me playing for YouTube than anything else. It wasn’t until my final years of school where I was being taught by a fantastic biology teacher who really inspired me through different practical courses, and recommending a fantastic magazine, Biological Sciences Review, which really brought the science I was learning in the classroom to life.
What made you want to pursue a career in your particular field?
I chose to study Biology at the University of Sussex as I wanted a really broad course that would allow me to focus in when I found parts I was interested in. In my first year I became fascinated by Neuroscience. In my second year I was lectured on the role of different proteins in dementia by Professor Louise Serpell. I remember being sat in the lecture theatre and shown a healthy brain compared to an Alzheimer’s disease brain, and the stark contrast shocked me. I must have asked about six questions in that lecture and stayed behind after to discuss further with Louise. After these discussions, we decided to apply for a project grant for me to work over the summer in her lab. We fortunately received funding from the Alzheimer’s Society and the Society of Biology for me to work on a project exploring Amyloid-β and tau interaction in Alzheimer’s disease pathogenesis. In this project, I had the pleasure of working in the Serpell Lab being supervised by a PhD student (now Postdoc in the lab), Mahmoud Bukar-Maina, who taught me everything about different biochemistry techniques and was incredibly patient with me while I was learning! I carried on this project into my final year focusing more on the nuclear localisation of tau after treatment with Amyloid-β. The two projects with Louise really cemented my decision to study for a PhD in dementia research. Louise was incredibly helpful in suggesting different potential supervisors and reading over lots of applications! I found a PhD based in Manchester, working in The Hooper Lab under the supervision of Professor Nigel Hooper looking at the cell biology of dementia. After interviews and visiting the lab, I realised this was the best fit for me and now I’m here doing this interview!
Tell us more about the Running Down Dementia challenge, what's it all about and what inspired you to get involved?
The idea is to run 100km before August 31st, raising £100 for Alzheimer’s Research UK, the biggest charity in the UK funding ground-breaking research into dementia. I have decided to do it along with 11 current, alumni, or honorary members of Nigel Hooper’s or Stuart Pickering-Brown’s lab at the University of Manchester, hence the name, Team HoopSPB.
You describe yourself as "a keen communicator of science". Do you think that there is a lack of communication around science to the wider world, and if so what do you think needs to be done to address this?
I’m speaking purely for dementia research here, but the fact that only 23% of the UK population understand that dementia is a disease and not a normal part of aging suggests that there needs to be a massive shift in the types of science communication we are doing. As scientists, it is our duty to go and disseminate our work as actively as possible, it doesn’t have to be at events or in schools, even small things like chatting to the person who is sat next to you on the bus can make a big impact.
What advice would you give to someone just starting their PhD?
Three things:
Get involved in everything possible, be it public engagement, conferences, teaching and anything offered to you early on, find out what interests you and focus on these alongside your PhD
You can have a life outside of your PhD
Celebrate your successes, even if they are small!
What are you enjoying most about your PhD?
The research I do fascinates me, I’ve found that I really enjoy adapting different methodologies to my project, I also love working alongside such amazing scientists!
What does a typical day in the lab look like for you?
My lab will laugh at my answer but generally Western blotting, preparing samples for Western blotting, or analysing my Western blotting data whilst listening to trance music. I also do quite a lot of cell culture, here I express different constructs of tau and tau fragments into cells and study what they do in the cell.
If you weren’t a scientist, what do you think you’d be doing?
Teaching, maybe history or economics as I loved these subjects at school.
Outside the lab, what do you enjoy doing?
I love going to gigs and DJ sets, I find live music to be a really good escape from the PhD for a bit!
What is it about your field of research that gets you most excited?
The fact we are so close to finding a new disease-modifying treatment for different types of dementia.
What do you think are the biggest challenges currently facing life scientists and their work?
Access to reliable models of disease. This is something we are working on in the lab with the development of iPSC-derived neural models and 3D culture systems to mimic what happens in the brain.
Which scientists working today do you most admire, and why?
I have been extremely fortunate to work alongside some fantastic and inspiring scientists, these people have been the main reason that I enjoy working in the lab so much!
What’s your favourite science quote?
“We are just an advanced breed of monkeys on a minor planet of a very average star. But we can understand the Universe. That makes us something very special.” -- Stephen Hawking:
What do you think is the greatest scientific discovery of all time?
Vaccines. They have prevented countless numbers of deaths and diseases, all because of one man and a cow.
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Thank you so much, James! Best of luck with both your research and your running challenge.
Follow James on Twitter @TweetwithQuinn
Follow The Hooper Lab on Twitter @hooperlabmanc
Connect with James on Linkedin: https://uk.linkedin.com/in/james-quinn
Find James on ResearchGate: https://www.researchgate.net/profile/James_Quinn8
Read Jame’s Review, Tau Proteolysis in the Pathogenesis of Tauopathies: Neurotoxic Fragments and Novel Biomarkers: https://www.ncbi.nlm.nih.gov/pubmed/29630551
Make a donation to Team HoopSPB: https://runningdowndementia2018.everydayhero.com/uk/team-hoopspb
