For the Sleep Research Coordinating Committee presentation at the Dec, 2024 SDRAB meeting, Dr. Michael Sesma, an NIH health science administrator, presented a portfolio of work of several labs across the country that are studying various aspects of circadian rhythms. Here are some of highlights from Sesma's talk:
Harvard University's Lane Lab - led by Dr. Jackie Lane - is working on the Circadia study. It is developing a rich phenotyped resource with data collected from patients using its at-home circadian phase assessment toolkits. The study is analyzing the data it gathers - as well as data from existing biobanks - to investigate large-scale populations in order to identify individuals with extreme circadian behavior. This will result in the identification of new genes and pathways associated with CRDs - revealing possible loci to target in the development of therapeutics.
Dr. Sesma reports that a postdoc from the Lane Lab presented about Circadia's progress and toolkit at the SRBR conference in May 2024, and it caused a "rumble" in the audience as meeting attendees wanted to know how they could be part of the study and obtain the toolkit.
Dr. Carl Johnson is a professor of molecular physiology and biophysics at Vanderbilt University and leads the Johnson Lab. The lab has been working on elucidating the principles of the circadian clocks at a biophysical and molecular level in cyanobacteria for years.
Cyanobacteria are prokaryotes - they are single-celled organisms that lack a nucleus. The cyanobacteria circadian clock has the features of any other circadian system that is studied - it is a free running clock with a 24-hour cycle. This ancient clock - possibly primordial - exhibits temperature compensation and responds to changes in the environment so it can be reset.
Light sensitive components of the cyanobacteria do not exist so scientists are able to do experiments with cyanobacteria without concern about light exposure. "The fact that cyanobacteria has a free-running clock without that stimulation is pretty important," Dr. Sesma noted.
Dr. Jeff Jones is an assistant professor of biology at Texas A&M and leads the Jones Lab. The lab seeks to understand how circadian input from the SCN is encoded by target neurons to generate behavioral rhythms that peak at different times of the day in distinct animals.
Dr. Jones uses genomic editing of clock genes, in vivo and ex vivo imaging of rhythmic neurons and machine learning analysis of behavior to explore circadian output circuitry in the nocturnal laboratory mouse and the diurnal African striped mouse.
From this work, they have learned that molecular and neural activity rhythms in the SCN peak at similar times whether the animal is nocturnal or diurnal.
Identifying the genes, neurons and circuits that regulate the timing of behavior in both types of mice will provide a framework for understanding the biological basis of chronotype in humans and the etiology of CRDs.
Dr. Sesma presented recent collaborative work by Dr. Carrie Partch, professor of chemistry and biochemistry at UC Santa Cruz, Dr. Andy LiWang, professor of chemistry and biochemistry at UC Merced and Dr. Susan Golden, professor of molecular biology at UC San Diego.
Partch leads the Partch lab, which seeks to understand how organisms' molecular clocks synchronize their physiological processes into rhythms that coincide with the solar day, providing enhanced evolutionary fitness by coordinating timing of integrated biochemical processes and optimizing energy utilization.
Circadian clocks provide a biochemical representation of local time inside cells and control the timing of gene expression in anticipation of sunrise and sunset.
Together, the scientists reconstituted the circadian clock of cyanobacteria in a test tube. This enabled them to study rhythmic interactions of the clock proteins in real time and understand how these interactions enable the clock to exert control over gene expression.
In cyanobacteria, a circadian oscillator comprised of three Kai proteins - KaiA, KaiB, and KaiC - relays temporal information downstream through two kinases, SasA and CikA, to regulate the transcription factor RpaA.
We are delighted and encouraged to learn about the range of research projects devoted to studying what influences circadian clocks beyond light exposure for a range of organisms - from single cell to human.
