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The biological timing system in healthy volunteers and patients with neuropsychiatric disorders


Research in our laboratory focuses on the timing system not only in healthy volunteers but also in patients suffering from disorders associated with disrupted sleep pattern. The aim of our projects is to find connections between the functional state of the timing system and those disorders.

How we study the human timing system in vivo

The timing system in healthy volunteers

To assess the functional state of the timing system, we collect samples of saliva in few-hourly intervals

Chronotype
Human chronotype defines the preference of the sleep timing. The preference widely differs among individuals. The subjects with extreme early chronotype ("larks") awake at the time when subjects with extremely late chronotype ("owls") fall asleep.

during the whole day to measure the levels of hormone melatonin. Besides the saliva we collect samples of the buccal mucosa by gently scrubbing the inner cheek, in which we measure the levels of clock genes expression. We can determine various parameters of the functional state of the timing system from the time-curves of those rhythmical markers. In healthy subjects, we can determine their chronotype.

The timing system in patients – collaboration with clinics

We use the methods described above to study the circadian system in patients with disorders associated with sleeping problems. We study the timing system in both adult patients (e.g. suffering from bipolar disorder, Alzheimer disease or hypersomnia) and children (e.g. with ADHD, mucopolysaccharidosis or Smith-Magenis Syndrome).

 

 

 

How we study the human circadian system in vitro

Some parameters of the human timing system can be assessed also in vitro. We can grow the cell cultures from the human skin biopsies. Then we genetically modify the cells in the culture. This allows us to continuously monitor expression of selected clock gene in real time and therefore to watch the clockwork in action. This procedure can be done both in patients and healthy volunteers.

 

 

Daily rhythmical expression of clock gene Bmal1 measured in fibroblast cultures from skin biopsies of two healthy volunteers. The rhythm runs faster, i.e. with a shorter period, in the volunteer depicted in blue compared to the volunteer depicted in red.