This month, the EI team spoke to Dr Tilo Kunath, SynthSys member and Reader in Regenerative Neurobiology in the School of Biological Sciences, about his work combating Parkinson’s disease.
From primary school science fairs to the forefront of stem cell research, Dr Tilo Kunath has sustained a passion for science and a tireless curiosity that has driven him to make crucial advancements in the fight against Parkinson’s disease, a degenerative neurological condition for which there is currently no diagnostic test and no cure.
Tilo recalls that his love of biology took root at a young age; he was fascinated by living things and how they worked, and he loved to participate in school science fairs. At one memorable fair in primary school, Tilo and a friend successfully froze and reanimated cockroaches using his mother’s freezer without her knowledge. The boys were delighted with the results and proudly displayed their very lively cockroaches at the fair… until they were unexpectedly confiscated by the teacher for violating the school’s health and safety policy. An early lesson in the unpredictability of scientific experiments.
Tilo is now “100 per cent dedicated to Parkinson’s research”, a statement borne out both in his achievements to date and in his commitment to the Parkinson’s community, but his steadfastness was arrived at after a period of youthful uncertainty and the occasional false start. The first in his family to go to university, Tilo enrolled at Queen’s University in Kingston, Canada because a friend of his was going and university seemed like the next logical step.
It was during his time as an undergrad that Tilo realised for the first time that being a scientist was a viable career path, and so upon graduating with a BSc in Biochemistry Tilo embarked on an MSc in cancer research at McGill University. He then followed his fascination for embryo development and enrolled for a PhD at the University of Toronto under the mentorship of renowned embryologist Professor Janet Rossant.
Having pivoted from cancer research, Tilo was enjoying his doctoral studies in embryology, unaware that the course of his career was about to be rerouted. When pioneering stem cell scientist Professor Austin Smith gave a guest lecture at the University of Toronto, Tilo was blown away by his passion and unapologetic focus on the basic biology of stem cells. Right then he knew that Professor Smith’s lab at the University of Edinburgh was the only one in the world he wanted to work in.
The only problem? Austin Smith wasn’t hiring at the time. “I sent him pleading emails,” Tilo recalls, “I went as far as getting Janet Rossant to contact him, but he just didn’t believe that I was serious about moving to the UK.” Undeterred by his initial lack of success, Tilo continued to contact him by email and telephone until he finally convinced the Professor that he was genuinely committed to working in his lab, if given the opportunity. The campaign paid off, and after interviewing Tilo in December 2002 Austin Smith hired him as a post-doctoral fellow at the Institute for Stem Cell Research (ISCR) at the University of Edinburgh.
During his time working under Austin Smith, Tilo dedicated himself to understanding how stem cells become neural tissue, a process called neural induction. Although his research was not directly on Parkinson’s disease, Tilo’s work was part-funded by the Parkinson’s Disease Society (now Parkinson’s UK), which might go some way to explaining the leap of faith he took next.
When Tilo’s postdoctoral fellowship at the ISCR was coming to an end he applied for three other fellowships; two standard fellowship schemes that would allow him to continue his work in primitive neural induction, and one speculative application to Parkinson’s UK. He proposed making induced Pluripotent Stem (iPS) cells from Parkinson’s patients to study the disease more closely, the catch was that he had no experience of making iPS cells, no preliminary data, and no access to patients.
Shortly before Parkinson’s UK invited him to interview, Tilo serendipitously met UCL Professor John Hardy, who had a collection of rare Parkinson’s patient fibroblasts in his lab that, luckily for Tilo, he was willing to share. Tilo’s plan of attack for creating iPS cells from the fibroblasts of rare genetic Parkinson’s families wowed the panel and secured him the Parkinson’s UK Senior Fellowship. Within two years, Tilo had successfully created the first human iPS cells in Scotland and published a groundbreaking paper on how producing iPS cells from Parkinson’s patients unlocks the next phase of research into the disease.
Since the beginning of that fellowship, Tilo has thrown himself not only into Parkinson’s research, but into engaging with the Parkinson’s community. He and Professor Ken Bowler were instrumental in the formation of the Edinburgh Research Interest Group (ERIG), organised so that people with Parkinson’s interested in research could meet, work together and further the cause of Parkinson’s research. He and Professor Bowler hosted regular patient visits at the Centre for Regenerative Medicine, where Tilo’s lab is based, for members of the Parkinson’s community to hear about progress being made and ask questions of the researchers.
A keen runner, Tilo has taken part in several fundraising and awareness-boosting runs for Parkinson’s, including a parkrun alongside friend and Parkinson’s patient John MacPhee that was featured in Jessica Ennis-Hill’s parkrun heroes series. John and Tilo even performed an Edinburgh Fringe show together in 2017, in which they posited how Parkinson’s can be eradicated as part of the Cabaret of Dangerous Ideas series. Tilo’s commitment to and support of the Parkinson’s community has not gone unnoticed, and in 2019 he was presented with the prestigious Tom Isaacs Award in recognition of the significant impact he has made on the lives of people living with Parkinson’s.
“Working on research that could impact the lives of people with Parkinson’s is extremely motivating”, Tilo says, “and interacting with the patient community can influence the direction of my research.” Indeed, it was after one meeting with the partner of a Parkinson’s patient that Tilo embarked on one of the most exciting research projects of his career. At a Parkinson’s Awareness Week event in 2012, Joy Milne asked Tilo why smell is not being used as a means of diagnosing the disease.
The question struck Tilo as odd, and even months after the event he couldn’t get it out of his mind. Eventually, the same curiosity that had led Tilo to put insects in the freezer as a small boy compelled him to follow up with Joy and find out more. When he did, she told him that she had detected a change in her husband Les’s scent over a decade before he was diagnosed, and that she noticed the same distinct smell when attending meetings organised by Parkinson’s UK. Tilo contacted colleague Professor Perdita Barran, then a University of Edinburgh researcher who is now based at the University of Manchester, to collaborate on a project to identify what Joy was smelling.
After conducting smell tests that confirmed Joy’s ability to detect Parkinson’s from smell alone, the team explored the possibility that chemical changes in a patient’s sebum – the oil in their skin – are responsible for the odour. A breakthrough in 2019 established that the sebum of Parkinson’s patients has a complex chemical signature, and one that alters as the disease progresses. This means that a simple skin swab could potentially be used not only to diagnose Parkinson’s, but to monitor the development of the condition. Work on refining the test is ongoing, but in 2021 the research team, including Tilo and Joy, were awarded the Analytical Division Horizon Prize: Robert Boyle Prize for Analytical Science, a prestigious award that was presented to them by the Royal Society of Chemistry.
Tilo’s research has been at the vanguard of the fight against Parkinson’s disease for nearly 15 years, but there is still a great deal of work to do. So what’s next? “If you had asked me five years ago if the protein Alpha-synuclein – which is in the pathology of Parkinson’s patients – is good for anything I would have said ‘no’, it’s a bad protein that only causes heartache and damage’. But we now have interesting data to say that Alpha-synuclein is involved in protecting us from viruses and protecting neurons from damage.”
In recent experiments, human neurons without Alpha-synuclein have been unable to control viral infections, whereas those with the protein have recovered, so Tilo is now working to understand why the protein is protective most of the time, but goes on to cause degeneration in the one per cent of the population who develop Parkinson’s. Whether his investigations will yield another breakthrough is uncertain at this early stage, but there is reason to be hopeful. After all, trusting his curiosity and following the science that excites him has always led to extraordinary results for Tilo.
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Photography: Maverick Photo Agency