Niamh O’Sullivan PhD, Neurogeneticist

Niamh O’Sullivan’s interest in science was kindled at a young age when she noticed the segregation of certain physical characteristics in her extended family. Learning that genetics controlled the segregation of these dominant traits, O’Sullivan entered the science program at Trinity College Dublin, Ireland. She specialized in genetics at a time when there was a lot of enthusiasm surrounding the future of human genetics; the first draft of the human genome project had just become available, opening up new potential to understand the function of genes. “I was very lucky to be in the right place at the right time.” O’Sullivan says. “It was a very exciting time to be studying genetics.”

The complexity of the brain and how genetics could be applied to better understand learning, memory, and cognition attracted O’Sullivan’s interest. After graduating from Trinity College Dublin, she moved to University College Dublin (UCD) to investigate transcriptional events underpinning learning-associated plasticity. Findings from her research supported the idea that memory consolidation requires coordinated waves of transcriptional control.⁶This research formed the basis of an academic-industry collaboration between UCD and Wyeth Discovery, the Applied Neurotherapeutics Research Group (ANRG). Within this collaborative group, O’Sullivan began her postdoctoral research. She used meta analysis of microarray data to investigate the underlying regulation of these transcriptional changes to identify a temporally regulated role for transcription cofactor regulation of structural plasticity in hippocampal neurons.^1,2,3,7This collaboration was a great training experience and exposed O’Sullivan to some of the differences between industry and academia research. “With more financial support, industrial researchers can focus their energies and resources when a particular target or candidate is identified. This can progress research in a particular avenue quickly.” says O’Sullivan. “On the other hand, in academia there is more freedom to explore data more thoroughly and follow-up several lines of study. The main thing I took away from working in the ANRG was the power of industry-academia collaborations. By applying both the focused resources and in-depth understanding to a particular research question, there is great potential for new discoveries.”

Towards the end of her postdoctoral research O’Sullivan received a UCD Horizon Scanning Grant to identify regulatory elements in a rat model of schizophrenia using next generation sequencing. “While it wasn’t a very big pot of money, it was my money. I was able to design and carry out a project, generate some interesting results and present my findings at national and international conferences.” says O’Sullivan. “To develop as an independent researcher it is important to be able to generate a track-record of receiving and managing grants successfully.”

Knowing that one of her primary career goals was to be based in Ireland, it was important for O’Sullivan to identify and develop a new research niche that would complement ongoing research and collaborative opportunities within Ireland. Recognizing a gap in basic neurogenetic models and the value that these model organisms could add to research of genetic regulation of neuronal function, O’Sullivan expanded her scientific toolbox by gaining experience with果蝇research. “果蝇have a very well characterized neuronal organization, and in果蝇larvae the lower motor neurons can easily be imaged from the cell body, all the way down along the axon, right to the synapse of the neuromuscular junction. You can study equivalent neurons in different animals or across different time points to look for differences as a result of genetic or pharmacological interventions” says O’Sullivan. In 2009, funded by a Marie Curie Fellowship, O’Sullivan moved to the University of Cambridge, UK, to study neurodegeneration in果蝇in Dr. Cahir O’Kane’s lab. Her research identified a role for endoplasmic reticulum shaping in progressive axonal degeneration and suggested a mechanism whereby mutations in endoplasmic reticulum–shaping proteins give rise to neurodegenerative disorders.^4,5

2012年奥沙利文被授予一个初级研究Fellowship at Imperial College London. Under this fellowship, O’Sullivan established an independent laboratory to study the role of the chaperone protein VCP in the neurodegenerative disorder amyotrophic lateral sclerosis (ALS). However, within a few months, O’Sullivan obtained a lectureship position in genetics and neuroscience at UCD and in 2013 she established her laboratory in the School of Biomolecular and Biomedical Science at UCD.

O’Sullivan’s Philosophy

Undergraduate College Advice
“现在许多大学在全球范围内提供专业undergraduate degrees. However, I would usually advise students to opt instead for a broad-based natural science course. This provides them with the opportunity to study a whole range of subjects such as zoology, botany, environmental science, genetics, neuroscience etc., which are scarcely discussed at school level. Within a general entry science degree program, students can usually spend a year or two taking classes in these different subjects before specializing.”

Postdoc Career Advice
“Many fellowships have quite tight eligibility restrictions on length of time post-PhD, leading to what’s known as the ‘post-doc clock’ starting the day you start as a post-doctoral researcher. It’s important to be aware of this, but don’t despair if you haven’t been focused on this. I blew the post-doc clock right out of the water. In my first post-doctoral position I got a lot of great experience: I supervised students, I was quite mobile, I gave plenty of presentations and got involved in some lecturing, but I wasn’t developing my own career enough. You need to always be initiating projects that you can publish as a first author. After a few years, it became apparent that I needed to focus much more on generative papers and grant awards.”

On Funding and Career Development
“Trying to get any small amount of money is important, even if it’s just seed funding or a travel grant. Sometimes people can be in very wealthy labs and there isn’t that necessity to apply for these small pots of money, but it is important long-term to be able to show you have a track record of securing funding and doing something sensible with it. This will benefit you when you are applying for much bigger fellowships or grants. At postgraduate level, all PhD level students should be trying to apply for some travel funding to go to conferences or smaller grants to build up a funding track record.”

On Science Experience
“When I took up my second post-doc I already had 4 years of postdoc experience and had grown in confidence. Importantly, I was able to deal with things not going as expected and could change my approach to develop my research story slightly differently. During my career, I have met some other researchers, straight out of a PhD, who didn’t have the same skills to know what to do when research goes wrong. In my case, having more experience helped me to succeed and highlights that rigidly adhering to the ‘post-doc clock’ isn’t always the most important thing.”

On Establishing Independence
“There is a huge jump from being a senior postdoc with first author papers and being a principal investigator and getting last author papers. I’m now at the period where I am trying to get research together to generate final author papers, to establish myself as an independent researcher in my field. However, I need to apply for grants to get the money to do the research to write the papers. It is a complete catch 22! Right now I’m focused on generating publications - otherwise I’m just not going to get the funding I need to do the research that really excites me.”

On Academic Success
“Success usually comes about as a result of hard work but also often requires a bit of good luck. It can be disheartening to have job or grant applications rejected but you have to keep trying. Where possible, get feedback so that you can improve your next application. However, remember that luck is a factor too!”

References

1. 1. Monopoli MP, Raghnaill MN, Loscher JS, O’Sullivan NC, Pangalos MN, Ring RH, von Schack D, Dunn MJ, Regan CM, Pennington S, Murphy KJ (2012) Temporal proteomic profile of memory consolidation in the rat hippocampal dentate gyrus. Proteomics 11:4189–4201.
2. 2. Murphy KJ et al. (2010) Temporal dysregulation of cortical gene expression in the isolation reared Wistar rat. J Neurochem 113:601–614.
3. 3. O’Sullivan NC, Croydon L, McGettigan PA, Pickering M, Murphy KJ (2010a) Hippocampal region-specific regulation of NF-kappaB may contribute to learning-associated synaptic reorganisation. Brain Res Bull 81:385–390.
4. 4. O’Sullivan NC, Dräger N, O’Kane CJ (2013) Characterization of the Drosophila Atlastin Interactome Reveals VCP as a Functionally Related Interactor. J Genet Genomics 40:297–306.
5. 5. O’Sullivan NC, Jahn TR, Reid E, O’Kane CJ (2012) Reticulon-like-1, the drosophila orthologue of the hereditary spastic paraplegia gene reticulon 2, is required for organization of endoplasmic reticulum and of distal motor axons. Hum Mol Genet 21:3356–3365.
6. 6. O’Sullivan NC, McGettigan P a, Sheridan GK, Pickering M, Conboy L, O’Connor JJ, Moynagh PN, Higgins DG, Regan CM, Murphy KJ (2007) Temporal change in gene expression in the rat dentate gyrus following passive avoidance learning. J Neurochem 101:1085–1098.
7. 7. O’Sullivan NC, Pickering M, Di Giacomo D, Loscher JS, Murphy KJ (2010b) Mkl transcription cofactors regulate structural plasticity in hippocampal neurons. Cereb Cortex 20:1915–1925.