Eleanor discusses her PhD project using multi-omic approaches on population cohort datasets, and those who have inspired and helped her scientific journey to date.
Dr Eleanor Conole is currently a Postdoc in the Lothian Birth Cohorts group. She did her PhD at the University of Edinburgh funded by the Wellcome Trust on the Translational Neuroscience programme, supervised by Dr Simon Cox, Professor Riccardo Marioni, Professor Heather Whalley and Dr Veronique Miron.
Eleanor was awarded a presentation prize at the 2023 Edinburgh Next Generation of Genomics Symposium (ENGoGS23).
At ENGoGS, I presented some of my work on using a multi-omic approach to explore how signatures of inflammation associate with neuroimaging and cognitive outcomes at different stages of brain ageing. It summarised the main papers published from my PhD research which was set across three population cohorts that spanned the human lifespan. I was interested in how poorly characterised inflammation is at the population level, where we often rely on a single protein taken from a single blood test to infer someone’s baseline inflammatory status – and whether that masks inflammation’s true impact on brain health. When we think of inflammation we think of its cardinal symptoms (pain, redness, swelling, heat, reduced function, etc.). If you think of the last time you had a cold, or fell over and hurt yourself, you’ll be familiar with these characteristics. Those symptoms hint at how complex inflammation is at the molecular level: inflammation is not one thing – or one protein – and that means we don’t have a sole biomarker we can rely on to characterise it.
Clinicians use a range of measures to assess someone’s inflammatory status, and some of these don’t translate well to research settings in population cohorts. Recent advances in genomics offer a range of ways to profile chronic inflammation. My PhD focused on whether DNA methylation (DNAm) could be used to index inflammation, how it compared to protein measures, and how these related to aspects of brain health. We examined different approaches of measuring inflammation – from more traditional enzyme assays and higher sensitivity immunoturbidimetric assays, which measure one protein at a time, to proteomic platforms like Olink and SomaScan which can measure hundreds of proteins from a single sample simultaneously, to measuring DNAm from blood and saliva via microarrays. We looked how these associated with multi-modal neuroimaging modalities and measures of cognitive ability across different age ranges, and how different health factors and lifestyle choices influenced those relationships. I had a particular interest in how chronic inflammation related to the brain’s white matter, both in early life and old-age, so looked at these measures in relation to diffusion tensor imaging (DTI) measures of white matter health.
I did my BSc in Neuroscience at the University of Bristol, and after a brief return to the NHS, went back to do a Masters by Research in electrophysiology that looked at how cortical circuits mature during a critical period in early development. I then moved to Scotland to start the 4-year Wellcome Trust Translational Neuroscience PhD programme here in Edinburgh. After my PhD viva, I continued working in the Lothian Birth Cohorts group as a postdoc on the neurobiology of cognitive decline, funded by a NIH connectome grant. My current project looks at how we can use machine learning methods to assess how proteomic signatures of immune function relate to brain structure and connectivity in UKBiobank.
In May, I’m starting a 3-year junior research fellowship in Applied AI at the University of Oxford to continue working at this interface of genomics and neuroimaging.
It’s less of a what and more of a who. I’ve had some amazing teachers, mentors, and people I work alongside. Michelle Breeze, who always gave me extra books to read; Mike Ashby, who gave the best lectures, patiently guided my first shaky brain dissection, and told me I was capable of a PhD; postdocs in the labs I did summer projects in; Simon Cox, Ian Deary and countless others at 7 George Square for making my PhD and current postdoc so enjoyable…
Edinburgh in particular is overflowing with kind and amazing researchers. It’s the people in research who have made me want to be a researcher.
Dr Mike Shepherd, an organic chemist (1955 – 2014). He did his BSc in Chemistry at the University of Bristol, had a stint in industry at SmithKline Beecham (now GSK), before deciding he preferred the autonomy of research, and spent his PhD examining how benzocyclobutadiene can be used to construct aromatic rings, finishing his thesis in 1984. He then worked as lecturer for over two decades in London, while keeping his main focus as a synthetic chemist working on how to develop new penicillins based on clavulanic acid. He was also, more importantly, my dad.
Dad died of an aneurysm just before I started my undergraduate degree. He was my best friend and constant confidante. You could also ask him anything, and he’d respond enthusiastically with an in-depth answer; no questions were too abstract, too nonsensical, or too fundamental. I feel lucky to have been taught so early in life that if you have a question, not only is it worth asking – the pursuit of the answer is exciting. If I had a question he didn’t have an answer for, his reply was always: “Well, let’s find out”. I’m probably in science because every scientist I meet feels like a thread to him, and it’s an excuse to keep asking questions to interesting and brilliant people.
I’d give anything to have one more conversation with him. Every new breakthrough that happens in science and tech I want to tell him about. Maybe we’d talk about alpha fold, or how I’m now researching healthy ageing. Maybe it’s no surprise I’m so invested in people living well into old age, because I feel he was robbed of that (and I of him).
In 2013, I took a year out to work as a Health Care Assistant (HCA) and phlebotomist before I started my undergraduate degree, worked part time in the NHS as a phlebotomist and nursing assistant during my degree, then returned to the NHS after graduating with my BSc to work as an assistant sleep physiologist at the Bristol Royal Infirmary before starting my Masters. From working in those frontline healthcare roles, I have a particular interest in research that has direct translational impact. I really enjoy research projects working alongside clinicians and the kind of questions and directions that result from interdisciplinary research.
I feel beyond lucky to be working in such an interesting field today, but it’s not something I could have predicted or had mapped out at 18. There are lots of pivots and choices you make in academia that are hard to chart at the outset. All my degrees are in neuroscience, and My PhD is when I started working in genomics – before that, my only brief exposure to anything close to it was an OU course I took alongside my A-levels (SK195 Human Genetics and Health Issues).
If you like asking questions, working in science feels like a total privilege. Your day job can involve fascinating conversations with curious, passionate, and interesting people. Even better: you have the opportunity to work alongside them to find out things about how the world works. My advice is to read widely about others' research and talk to them about it – science is made up of the people who do it. If you’re a student, ask PIs if they can host you in their group or lab for a summer project, or if they know of any funding opportunities you might be eligible for.
I think the hardest parts of working in research are obstacles ancillary to research itself: funding, instability, and logistics – balancing short-term contracts, relocating, responsibilities that are outside of your control etc. Asking for help can also feel difficult when you’re under a deadline, or shouldering a lot of responsibility for a project you’re invested in. I had some caring responsibilities that came to a head during my thesis write-up with my mum’s terminal illness. I was really lucky to have an amazing support network – my thesis chair (Dr. Mike Baston), supervisors (Dr. Simon Cox, Prof. Riccardo Marioni, Prof. Heather Whalley, Dr. Veronique Miron), colleagues, and financial help organised by the directors and coordinators of the Translational Neuroscience programme. Their support was everything – and they’re the reason I now have a PhD.
I spend as much time as I can outside with people I care about. I like ice-climbing, trad-climbing, sport-climbing, bouldering, caving, skiing and running.
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