First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Hope Needs is first author on ‘ Aggregation-prone Tau impairs mitochondrial import, which affects organelle morphology and neuronal complexity’, published in JCS. Hope conducted the research described in this article while a PhD student in Prof. Ian Collinson and Prof. Jeremy Henley's lab at School of Biochemistry, University of Bristol, UK. She is now a postdoc in the lab of at Prof. Jeremy Henley investigating mitochondrial function and dysfunction (particularly mitochondrial protein import) in neurodegenerative disease.
How would you explain the main findings of your paper in lay terms?
Mitochondria provide most of the energy the cell needs to perform its functions. However, they can't do this without importing many of their protein components from elsewhere in the cell where they are made. Mitochondria have many specialised import pathways that carry out this process effectively. However, when this goes wrong, the mitochondria don't have the machinery they need to carry out their functions, including generating energy, which has detrimental effects on the cell. Several studies have shown that the toxic, aggregating proteins characteristic of neurodegenerative disease are associated with import dysfunction. In this study, we wanted to investigate whether a mutant form of Tau, a protein linked to neurodegeneration, has any effect on mitochondria, specifically their import machinery. We found that Tau associates with the import machinery, specifically with one component known as TOM40, and this blockage perturbs import. However, the cells can rescue their import function by forming structures that allow the transfer of healthy mitochondria from neighbouring cells. In neurons, the Tau variant induced changes that mirror what we see when we block import artificially, providing an intriguing link between Tau and import dysfunction that is relevant to neurodegenerative disease.
Were there any specific challenges associated with this project? If so, how did you overcome them?
My PhD project spanned two groups, led by Ian Collinson and Jeremy Henley. Connecting the mitochondrial import side with the neuronal side was challenging at first, particularly as I hadn't worked with primary neurons before, and they can be pretty temperamental cells. I was fortunate to have really experienced, supportive colleagues in both groups, whose expertise was invaluable to overcoming experimental challenges.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
When we did the Tau immunoprecipitations and found that TauP301L (the disease-prone variant) was associated with TOM40, that was really exciting! Those experiments took a lot of optimisation: from the protein expression to the mitochondrial isolations and the immunoprecipitations; we had been working on it for quite some time. Once we finally got it working and got such an intriguing result, we felt like we were really onto something and could see for the first time where the story was headed, which helped us come up with the next experiments.
Why did you choose Journal of Cell Science for your paper?
The project combined several distinct aspects: mitochondrial biology, import kinetics and neurobiology. We felt that Journal of Cell Science is a high-quality, interdisciplinary journal that highlights research spanning different areas of cell biology, so was a great fit for our paper!
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
Both of my PhD supervisors, Ian Collinson and Jeremy Henley, were excellent mentors throughout my PhD (and continue to be during my postdoc!). It was great to have input and support from both sides of the project, which has broadened my knowledge and expertise. Also, I was very lucky to join a collaborative and supportive research group with a broad range of expertise and great office chat.
What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?
I knew I wanted to pursue a career in science while doing my placement year in the third year of my undergraduate degree. I was fortunate to get a placement in a cancer research group at the University of Florence, Italy. My supervisor, Andrea Morandi, and the rest of the lab were so welcoming and taught me so much, despite my limited Italian language skills when I first arrived. I had such an excellent year there that I set out to apply for PhD programmes as soon as I got back. I initially thought I would work in cancer research after this experience. However, the PhD programme I was on (Wellcome Trust's Dynamic Molecular Cell Biology programme) allowed me to carry out three rotation projects in my first year. During this year, I became interested in neuroscience, inspiring me to develop this project focusing on mitochondrial import in neurodegeneration.
Tell us something interesting about yourself that wouldn't be on your CV
I love surfing and head across the bridge to Wales for a surf whenever I can!
Hope Needs's contact details: School of Biochemistry, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.