Welcome to Hanna M. Ollila

Dr. Hanna M. Ollila is a FIMM-EMBL Group Leader at the Institute for Molecular Medicine Finland (FIMM), based at the University of Helsinki. Hanna specializes in the genetics of sleep and brain autoimmunity. In this interview, Hanna sheds some light on her field of research and elaborates on future plans for her newly established research group.

Dr Hanna M. Ollila. Photo: FIMM

Can you tell me a bit about your background? 

I have been in the field of sleep research for basically my entire scientific career. I am a cell biologist by training, and defended my PhD in the genetics of sleep in 2013 (at Helsinki, Finland) with Tarja Stenberg and Tiina Paunio. At the time, this was an exciting period for genetics. The first GWAS (genome-wide association study) had been published just a few years earlier, giving me access to lots of data from the Finnish population. 

We conducted one of the first GWAS studies in sleep duration. In that paper, using simple pathway analyses, we showed that sleep duration overlapped with depression and cardiovascular disorders. I presented our very first findings from the second year of my PhD in 2009 at the annual American Academy Sleep Medicine meeting in Seattle. The director of the Stanford Sleep Center, Emmanuel Mignot, saw my presentation and offered me a postdoc position. We kept in touch and after completing my PhD, I decided to join Emmanuel Mignot’s research team for a postdoc, specializing in sleep and autoimmune disorders. During that time I met Richa Saxena at the Broad Institute and Jonathan Pritchard at Stanford University. For the following year we explored which genetic variants contribute to sleepiness in the normal population and how those variants lead to functional changes at the cellular level.  

This collaboration really ignited the sparks for those ideas that my lab is focusing on right now.

What got you interested in the genetics of sleep?

It’s actually an interesting story from when I was in high school. I had a discussion with my friends about sleep and the next morning I saw an article in Helsinki’s main newspaper with the headline “Adenosine is a neurotransmitter that puts your brain to sleep. A Finnish Harvard professor, Tarja Stenberg, had discovered that a neurotransmitter called adenosine accumulates in the brain during wake times and, once there is enough of it in the brain, you need to go to sleep to clear it off. It turned out of my friends actually knew Tarja and I still had the sleep article from back in high school, which I had showed to my friends at the time. It was a funny coincidence and made me apply for a PhD within the genetics of sleep in her research group, so Tarja then became one of my PhD supervisors.

Sleep is a reasonably general biomarker that is affected in a variety of diseases. For instance, sleep disruption increases the risk of cardiovascular disorders, increases perceived stress and decreases mood. Another interesting aspect is that when diseases occur, sleep patterns begin to change. 

When we have an infection, we sleep much more, but when you have poor sleep your risk for infections is higher, so it works both ways

It is natural to experience occasional sleep problems; they are part of stress responses or can be affected by what is happening in everyday life. However, when people experience prolonged or severe sleep problems or even sleep disorders, they do not necessarily seek help. This is partially due to the way we are trained to think; when we are tired, we think we are lazy. Even when suffering from a fairly severe sleep disorder, one might not even seek help because we are trained to think that we can power through the tiredness with a couple of cups of coffee. There have been changes to the this perception over the past decade, but more change and awareness about sleep disorders are needed. 

What questions are you setting out to address with your research and what are you working on at the moment? 

There are many basic questions that remain unanswered within sleep research. To start with a big one is of course to answer “Why do we sleep” or “How much sleep do we need”. Sleep is also about rhythms, and this circadian rhythmic behavior is the reason why we are hungry around noon and tired in the evening. When we do not have yet a full picture of many of these sleep disorders it is great to be able to utilize large scale data. For example, the FinnGen project and UK Biobank, which both have ICD codes (International Statistical Classification of Diseases and Related Health Problems) for diseases, make it possible to assess different kinds of sleep disorders, the environment for risk factors, and the biological risk factors using genetic and epidemiological tools.  

I am excited about all the different kinds of sleep disorders and the very basic mechanisms of sleep. However, there are many different hypersomnia conditions that remain unresolved at a large scale. Type-1 narcolepsy is one disorder that is highly studied within severe sleep disorders. Narcolepsy is a sleep disorder which involves the loss of brain cells that regulate wakefulness through an autoimmune attack. The loss of these cells leads to highly fragmented wakefulness and sleep; you are basically severely sleep deprived.

We have identified several genetic factors and environmental risk factors that predispose people to narcolepsy, but I think it is time to move forward and expand the scope to include other hypersomnia disorders, such as type-2 narcolepsy, chronic fatigue syndrome. I also think attention is needed for more controversial sleep disorders that people don’t necessarily know so much about. It is equally important to assess how prevalent these diseases are, and what the comorbid traits are that align with these disorders.  

When investigating diseases such as chronic fatigue syndrome, we think they are rare but when we evaluate the data, we realize that the disease is underdiagnosed, For instance, the diagnostic delay in narcolepsy cases used to be over seven years, but since the disease has received more attention recently, the diagnostic delay is substantially shorter. There are now approved novel drugs that target the key neurotransmitters or their receptors. Essentially, patients get the diagnosis and the treatment much more quickly. 

What methods do you use in your research? 

Currently, we are collecting information about sleep using questionnaires, validating findings in collections with clinical gold-standard sleep disorders and then connecting these measures with a variety of biological measures, such as genetic data. This allows us to examine the spectrum of sleep disorders from normal and relatively benign occasional issues, to debilitating sleep disorders. Surveys are a great tool to study the general population, as people usually know whether they feel refreshed in the morning. If they don’t, they either have a sleep problem, they sleep too little, or they sleep at the incorrect time of the day. 

The Finnish population samples have a lot of sleep questionnaires already in place that my research team can use. My team has also built our own questionnaires that are accessible online. The team uses clinically-validated questionnaires and scales for sleep quality and severity of symptoms. In addition, the questionnaires include untraditional questions such as “what kind of dreams do you have?” which tap into  features of sleep and dreaming that have attracted less attention before. Besides genetic epidemiology of sleep and working on large scale datasets, we combine our research with functional follow-up studies to assess the outcomes in the relevant tissue or relevant organism model.  

There are surprisingly many people interested in sleep research, and the current COVID-19 pandemic has naturally increased interest in infectious and brain autoimmune diseases as well.

On one hand we can examine those critical mechanisms that contribute to neuronal loss in brain autoimmune disorders like narcolepsy. On the other hand the next questions are in characterizing those mechanisms that control those sleep disorders that have not necessarily obtained so much attention. 

Could you tell me a bit about your group at FIMM?

I found recruitment process great and I received so many outstanding applications from around the world. Since starting my group, I have built up a team that includes a postdoctoral fellow from Sweden, Martin Broberg, and another postdoctoral fellow, Samuel Jones, joining in September from the UK. I also have two PhD students, Viola Helaakoski and Anniina Tervi from Finland, and one visiting researcher, PhD fellow Nasa Sinnott-Armstrong, who is primarily based at Stanford. Viola did a bachelor in Law and a masters in neuroscience at Kings College. Martin has transitioned to a more senior role in my group and Samuel has already participated in most of the sleep GWAS at the UK biobank, even before joining my group. Anniina has a solid functional biology background and will be a great asset in validating our genetic findings in functional models. 

What are your goals for the first phase as a FIMM-EMBL group leader?

One of the main goals is to further investigate the prevalence and the basic risk factors for sleep disorders and raise the understanding of sleep disorders, especially for people who suffer from insomnia or who are constantly tired during the day and are not aware of possible treatments.  

I’m not a clinician, but I think there is a good opportunity to raise awareness through my research for these aspects.

I want to further investigate some of the other hypersomnia disorders and examine their comorbidities such as, are there risk factors that lead to the development of narcolepsy or hypersomnia in general? Which disorders and diseases do these individuals then develop? This is relevant when the disease is managed in terms of what the risk factors are that doctors need to be aware of to treat alongside. This means that not only the sleep disorder is treated but the implications that come along with the disorder are also treated. 

Can you share a defining moment as a scientist?

Most people understand how it feels when you cannot fall asleep. Also, you do not have to be a scientist to understand how it feels to be exhausted. Therefore, it is easy to connect with people about sleep. These every day interactions also remind me of the importance of my research.   

Click here to learn more about the genetics of sleep, circadian rhythms and brain autoimmunity.

Learn more about group leader Hanna M. Ollila and her research team here.