Sridhar Jagannathan talks about his research into the mechanisms and function of sleep.
Studying the human brain is like looking at Mars through a telescope. You kind of know what is there, but you have to guess certain things.Sridhar Jagannathan
What is the function of sleep? What happens when we fall asleep every night and why do we spend so much of our lives essentially parked?
These are just some of the questions being addressed by Sridhar Jagannathan’s research. Sri  began his PhD at Cambridge with an interest in how people lose consciousness naturally its effect on attention and whether the process of losing consciousness can be described in a mathematical model.
However, halfway through he realised that the human brain is too complex for his questions and that the current technology cannot answer them in sufficient detail.
He says: “After I published my first paper on my research on humans, I realised that to understand how something works you have to break it down and put it back together again, but the human brain is too complex for us to be able to do that now.”
During that time Sri read Francis Crick’s book, What Mad Pursuit: A Personal View of Scientific Discovery, which discussed how scientific advances are made: through being able to clearly define a problem and having access to technology that can be used to test your hypothesis.
He decided that he needed to work on smaller, less complex organisms and travelled to Australia to study fruit flies. His PhD thesis on how sleep works was therefore based on both humans and fruit flies.
“Many people think flies are stupid, but they are really smart and they have been important for understanding fundamental biological processes in humans given that they show many human-like behaviours,” says Sri. He adds, for instance, that they seem to respond to anaesthesia in the same way as humans.
When he returned to Cambridge, Sri completed his PhD and moved to the Zoology department for a post-doc and focused on connectomics, the study of the brain’s structural and functional connections between cells. He took fruit flies’ brains apart and developed algorithms that helped in the reconstruction of neurons in the olfactory system, tracing their structural connections.
“I had to relearn everything in order to master the neuroanatomy of the fly,” he says. “Studying the human brain is like looking at Mars through a telescope. You kind of know what is there, but you have to guess certain things. Whereas imagine the level of detail a rover like Perseverance produced when it comes to the surface of Mars and its atmosphere. Similarly with the fly brain you can understand things at this level of detail.”
Sri has recently started a fellowship in Germany under the supervision of Dr David Owald at Charité Medical University, Berlin – “Dr Fly”. He had contacted Dr Owald after discovering his work on sleep, flies and memory. Dr Owald’s lab uses optical probes and microscopy to measure how neurons work rather than the usual tools like metal and glass electrodes used in electrophysiology.
Sri’s Walter Benjamin Fellowship, funded by the German Research Foundation (DFG) for early years researchers, will enable him to have a degree of independence to conduct his studies.
Just as Crick suggested, Sri has honed his focus to look at sleep and is planning to use advanced technology in the lab to crack the problem of the neurobiological function of sleep. He says investigating the basic circuit mechanisms of the brain could be an important step towards understanding how general anaesthesia works as well as the function of sleep. The latter could help with the development of treatments for sleep problems, a symptom of many diseases.
Sri was born and brought up in Chennai, India. His parents ran a small shop. His mother, who had not gone to university herself, took her children’s education very seriously. “She always encouraged me,” says Sri. That included sending Sri and his sister to school an hour away from home in order to get a better education.
Sri struggled with mathematics in the beginning, as he didn’t enjoy learning by rote. However, he improved and excelled at geometry in particular. When he left school he was not sure what he wanted to do. He opted for an engineering degree mainly by default and when he had finished he worked for close to four years writing/debugging algorithms in car airbag systems for Bosch. Nevertheless, he felt his problem-solving skills could be used to take on bigger challenges.
He became very interested in biomedicine – the newness of the field excited him and he was attracted to the potential for significant advancements in this field. He looked for master’s programmes that combined mathematics and biology. The Technical University of Eindhoven offered the possibility of learning how to apply maths to real world problems as well as research internships as part of its Electrical Engineering master’s.
Moving to Holland was a big culture change and it took a while to adapt. In the end, he started to really like the place and now considers it to be his second home.
Sri has always been keen to follow his interests and not keep to the well-trodden path with regards to his academic work. As such, throughout his academic career he has not been afraid to change track to pursue what interests him. In Holland he switched his focus to neuroscience after doing an internship at the Maastricht University Medical Centre.
His internship focused on people who had epileptic seizures but whose brains did not show the usual epileptic signals. He used mathematical techniques to look at whether there was a biological mechanism underpinning the seizures or whether they had a more psychogenic origin.
Sri became so interested in the project that he stayed for three months, publishing a paper on his research. At the end of his first year Sri transferred to the Radboud University to do a research internship at the Donders institute of Brain, Cognition and Behaviour. While there he also completed a minor in cognitive neuroscience.
After finishing his master’s he moved to Oxford University to work as a research assistant where he worked in the Department of Experimental Psychology on mathematical methods in neuroscience. Then he moved back to Holland to do consultancy work along with a science outreach project. He says that, coming from India, he had a different mindset to his peers and wanted to focus on some of the bigger questions.
He became interested in consciousness while working on the MindSong outreach project. It was run by the University of Cambridge’s Dr Tristan Bekinschtein, who was Sri’s PhD supervisor. The project involved using an EEG headset to transform brain activity into an experience of colours, lights and sound.
Sri is hoping that his next move – to Germany – will help him to shed new light on one of the biggest unsolved mysteries of neuroscience: Why do we sleep?