Case Study: Excellence Fellowship
Although sleeping is as universal as breathing, nobody really knows how or why we do it. This is the fundamental question Dr Jason Rihel has chosen to investigate. Why? Because sleep matters.
Doctors have described more than 80 separate sleep disorders, from narcolepsy to insomnia which can destroy quality of life. Dr Rihel’s research is funded by a UCL Excellence Fellowship – also known as, the UCL ‘Nobel incubator’. Members of the Fellowship programme are awarded support for three years and are allocated a senior academic to mentor them. The aim is to give the next generation of Nobel Prize winners the space, time and resource to make breakthrough discoveries that will transform our understanding of the world.
Time and space has been exactly what Rihel required. The Fellowship has enabled him to set up his own lab and follow his ideas wherever they may lead – in this case, to a tank of genetically manipulated fish. Certain sleep disorders occur because sufferers lose a set of neurons in their brains, which are responsible for stabilising wakefulness. Zebrafish also sleep, and they have exactly the same set of neurons. Rihel and his team observed the fish’s behaviour, using video cameras they produced data on how much the fish were moving and how much they slept. The manipulation of amyloid levels had dramatic and immediate effects on the zebrafish’s sleep.
“We know that Alzheimer’s patients often have sleep problems way before there is any evidence of dementia,” says Rihel. “So perhaps what’s happening is that amyloid beta is involved in normal sleep signalling. Maybe patients are starting a progression towards Alzheimer’s disease when amyloid beta starts to form these plaques. Maybe there’s a special signature to this kind of sleep that might be an early biomarker, aiding early diagnosis. That’s speculative – but we now know it’s a possibility.”
Rihel also used the Fellowship to explore sleep disturbance and autism. The team created zebrafish with the genetic disruptions that are known to be risk factors for autism, and observed the results. During the day, the fish behaved normally – but at night, they were hyperactive. Then Rihel’s team introduced drugs into the fish’s water. “We were able to find drugs that bring down the night-time hyperactivity to normal but have no effect on the day activity,” he says. “And so the possibility exists that we might be able to find drugs that have an effect on human patients.”
This would have a huge effect on quality of life for millions of people. “Surveys of parents of autistic children say that managing sleep problems is a big issue,” says Rihel. “If you improve sleep, maybe you make some of the symptoms, like hyperactivity during the day, more manageable as well.”
These experiments are just the beginning. The Fellowship, Rihel says, is all about doing ambitious things and answering those big questions. “It allowed us to try some crazier avenues. The amyloid beta project was an off-the-wall theory, which took a long time to pursue. It required long-term dedication by one of my postdocs to explore an idea that was always a little bit on the edge.”
And of course none of it – the lab, the zebrafish, the discoveries – would be possible without philanthropy.