Uncovering the mechanisms linking sleep and health

Meet new NCMM Group Leader, Charlotte Boccara, and learn about her plans for interdisciplinary sleep and systems neuroscience research at NCMM, and how she sees her science in the context of society.

6 people standing outside at a harbor
Dr. Charlotte Boccara and her research team
Dr. Boccara in a white lab coat and dark shirt working in the laboratory
NCMM Group Leader, Dr. Charlotte Boccara Photo: Ola Nordal

 

Why do we sleep?

This is the question that fuels Dr. Charlotte Boccara and her team at the Centre for Molecular Medicine Norway (NCMM) at the University of Oslo (UiO). Working at the intersection of developmental neurobiology, systems neuroscience, and technology development, Dr. Boccara’s research explores the links between sleep and healthy development. She explains what they are hoping to answer:

We all know sleep is important, but we still know very little as to why. All species sleep, but why has evolution kept a state where one is so vulnerable to attacks from predators? Why is it that if we do not sleep well enough our health deteriorates? How can we prevent that from happening?

Dr. Boccara is a neuroscientist, so her approach is to begin with the brain and develop innovative models of sleep deprivation. For this, she looks at brain oscillations on EEGs. She explains: 

The brain oscillations that one can observe on EEG readings reflect what we call brain states – whether you are, for example, relaxing or intensively engaged in solving a puzzle. They come from the synchronization of many neurons. The brain has mainly two types of neurons, excitatory and inhibitory, and, as with every system, you need a balance between the two. Inhibitory neurons are the orchestral conductor of your brain. They shape the patterns of activity, leading to brain waves on the EEG and avoiding cacophony.

Furthermore,  

There are different oscillations, depending on what you are doing, whether you're puzzling, or if you're relaxing. Or if you're running, or sleeping. In fact, each sleep stage, from REM to deep sleep, is characterized by specific oscillations. So one of our ideas is to map and inactivate specific sleep oscillations across brain development so as to understand their function. 

To this end, the group uses both experimental and computational approaches to study both impaired and healthy cognition in the young and the adult brain. 

The role of sleep in cognitive development

In today’s high-paced, technology-driven world there is a growing concern about chronic sleep deprivation, especially among children. It’s well known that sleep is essential for cognitive development. But how? The challenge is in addressing the mechanisms of how. 

Cognitive development can be quantified in animals whose sleep is modulated with the aid of optogenetics and chemogenetics. Optogenetics uses light and light-sensitive channels to control cellular processes, while chemogenetics employs chemically-engineered receptors and ligands. With these methods, Dr. Boccara can turn neurons on and off. She explains:

We’re trying to regulate the brain nuclei that control sleep transitions. With optogenetics, our idea is to make a closed loop by recording specific sleep patterns and then automatically inhibiting activity each time we observe them, enabling us to measure the effects on cognitive development. Chemogenetics works similarly to optogenetics, but it is more long-term regulation. 

Currently, they are testing and fine-tuning automatic recognition patterns based on artificial intelligence. The initial, promising results were presented at the recent biennial European neuroscience conference in Paris, FENS 2022.

Sleep and metabolic health

Parallelling a rise in obesity, the prevalence of metabolic syndrome, particularly in adolescents and children, is a growing public health concern. Coupled with chronic sleep deprivation, this puts teens at high risk for heart disease and type 2 diabetes later in life. Dr. Boccara and colleagues are setting out, with support from the Research Council of Norway, to examine the function of sleep in metabolic health. 

This highly ambitious project aims to measure brain fat tissue and neural communication during sleep. Such a feat could only be achieved through technology development and a highly interdisciplinary team. I will be collaborating with Prof. Ørjan Martinsen, a biophysicist from UiO, to engineer new ‘adipoprobes.’ We just recruited a PhD student, who is starting in September, to work on this project.

She continues:

Clues for the mechanisms are likely to lie in the epigenetic modifications that are linked to sleep. One of our collaborators is an expert in epigenetics and fat tissue energy storage - Dr. Nolwenn Briand at the Institute of Basic Medical Sciences at UiO. She has been working on maturation of adipose tissues and cells. And finally we have Prof. Phillippe Collas, from the same institute, a renowned specialist in epigenetics, on the team.

Technology development

Dr. Boccara’s group is also keen to engineer tools to improve their ability to analyze sleep. One of their newest approaches has recently won funding from the Research Council of Norway - ‘BrainChip,’ a miniaturized and wireless probe. The project involves two additional groups. One is led by Associate Prof. Torkel Hafting at the Institute of Basic Medical Sciences at UiO. The other is SINTEF, an independent research organization in Norway. Dr. Boccara explains:

To study sleep and cognitive development, I need to miniaturize things. I could do that myself to a certain extent, but our probe is tethered, meaning that there is a cable to the animal that we need to plug in. It’s working, but it’s not ideal for sleep or having the animal in natural conditions. We need a wireless probe, and that’s where my collaborators come in.

Dr. Boccara is also keen to develop ‘smart cages:’

While sleep architecture differs somewhat, sleep control and function are the same in rodents and humans. So, rodent models are essential in our research. We are looking toward smart cages that enable continuous monitoring so that we can gather much more accurate data around the clock. I'm trying to build this into the animal facilities at the University of Oslo. 

Reflections on collaboration, direction and motivation

Collaboration is key in Dr. Boccara’s interdisciplinary research, and she takes a pragmatic approach toward it, “in general, it’s better to add resources and focus on what you know how to do.” But she cautions that “scientific knowledge is expanding at a rapid pace and increasing field specialization. Yet one should be aware of ultra-specialization in research domains. If this happens, students, especially, can feel disconnected and lose motivation. We all need to see the bigger picture.”  

For Dr. Boccara, that bigger picture has shifted in recent years:

More and more, I ask myself ‘what is the best use of my work for societal benefit?’ Maybe it’s my age or the age we’re living in. My research needs to have meaning. Knowledge for the sake of knowledge is good, but I want to go a bit farther. We’re living in a time with a lot of troubles on the planet - politics, geopolitics, the climate, and so on. These thoughts have informed some of my decisions. 

One of those recent decisions was to set up her research group at NCMM, a translational science-focused center and member of the Nordic EMBL Partnership for Molecular Medicine:

Coming to NCMM meant that I came into a network of excellence with young PIs who are goal-oriented and face some of the same struggles as I do. I like the community feeling. We are trying to achieve something bigger, together. And to do that we are also part of the larger Nordic EMBL network.

says Dr. Boccara. While she is clearly driven by her research, her looking toward the bigger picture also means that she is motivated to lead her team and to teach: 

I enjoy being a team, being with people. I want to do many things in science, but I am conscious of my limitations. I only have two hands and one brain. The only way to reach my ambitious goals is to do it with many different people. I don't have all the competencies for it myself. Therefore I must build, and support, a multidisciplinary team, where people are more clever than me.

She continues: 

It’s my role to guide, mentor and focus on the growth of those in my group. I want people to be the best version of themselves, and I want to support them in their careers. I try to have career development plans in place. And, I emphasize networking, it's important to network with your peers, and up and down in seniority. 

With these strong motivations and with ‘sleep’ finding its way into mainstream headlines on a nearly daily basis, Dr. Boccara’s research has a clear impact on society. As she sums it up:

I think that future health care, especially around sleep and cognition, is going to be tailored to environmental and lifestyle factors. For example, wearables can have a big impact. We hope that our findings will contribute not only to continued research on sleep and neurodevelopmental disorders, but also to public debate and to providing incentives for guidelines that encourage healthy sleep habits.

Brief career summary

Dr. Charlotte Boccara was initially trained in cellular biology and physiology (BSc, 2003) and neuroscience (MSc, 2005) at the Université et Pierre Curie in Paris, France. She completed a PhD degree in neuroscience at the Faculty of Medicine and Kavli Institute for Systems Neuroscience at the Norwegian University of Science and Technology (NTNU) in Trondheim, Norway where she worked with Nobel Prize winners Profs. Edvard and May-Britt Moser developing cellular tools to record cognitive maps. After a maternity leave, she received her PhD degree in 2014. From 2012 to 2016, she was a Postdoctoral Researcher working with computational tools to decode sleep and decipher brain code with Prof. Jozsef Csicsvari at the Institute of Science and Technology Austria. She then spent two years (2017-2018) as a Research Associate at the Centre for Developmental Neurobiology at King’s College London in groups led by Profs. Oscar Marín and Beatriz Rico, developing tools to model neurodevelopmental disorders. In 2018 she received a prestigious Marie Skłodowska-Curie Actions Individual Fellowship for postdoctoral work hosted by Prof. Johan Storm at the Institute of Basic Medical Sciences at the University of Oslo. With an award from the Research Council of Norway in 2019, she became an independent project leader in 'Sleep, Cognition and Development' in the same institute. Since April 2022, Dr. Boccara has been a Group Leader in Systems Neuroscience and Sleep at NCMM. She was recently part of two teams awarded a total of 45 million NOK from the Research Council of Norway for collaborative studies on sleep and metabolic disorders and technological developments. 


The article is published as part of the “Behind the Science'' profile series, taking an in-depth look at a scientist or group within the Nordic EMBL Partnership.