22.1. 2019, Neurohumorální regulace

PhD project:  Circadian clocks in the brain – their function and mechanisms of resetting

The mammalian circadian system is composed of cellular oscillators which are mutually synchronized by external light/dark cycle to provide our organism with temporal organization essential for optimizing physiological functions according to actual daytime. The system is orchestrated by the principal clock located in the suprachiasmatic nuclei of the hypothalamus which receives the information about the external light/dark cycle and conveys the information to other clocks in the brain and periphery. In the brain, clocks are located also in other regulatory areas in hypothalamus and other parts and are exposed to multiple inputs which may be in conflict with the information about external environment. This could happen due to various lifestyle factors, such as irregular daily regime, exposure to light at night, shift work, sleep deprivation, stress, etc., but also due to the pharmacotherapy. These factors may affect the function of these circadian clocks. Therefore, it is important to elucidate the role of the clocks in various brain areas, their sensitivity to the disturbing factors and mechanisms of their resetting.

The PhD project aims to characterize properties of the circadian clocks in the brain, their sensitivity to environmental factors and drugs, and to unravel mechanisms of their resetting. The studies will employ the animal models, such as the laboratory rats and mice, including transgenic mice model. To achieve this goal, broad array of molecular and behavioral techniques used in the circadian field, including the real time recording of the clock gene expression in organotypic explants of the suprachiasmatic nuclei, hippocampus and other brain areas will be employed.

Candidate’s profile (requirements):

The candidates should have the Master's degree or equivalent in one of the fields: physiology, neuroscience, molecular biology, biochemistry, medicine or related fields, or they should be expecting to obtain their degree this year. Candidates should be fluent in English with good writing skills. Previous experience with biostatistics, in vivo models (mouse, rat) and molecular biology techniques is considered as an advantage.

Relevant publications:

Shrestha TC, Šuchmanová K, Houdek P, Sumová A, Ralph MR: Implicit time-place conditioning alters  

Per2 mRNA expression selectively in dorsal striatum without shifting its circadian clock. Sci. Rep. 2018, 8:15547| DOI:10.1038/s41598-018-33637-y

Polidarová L., Sládek M., Novosadová Z., Sumová A.: Aging does not compromise in vitro oscillation of the suprachiasmatic nuclei but makes it more vulnerable to constant light. Chronobiol. Int. 34:105-117, 2017

Nováková M., Praško J., Látalová K., Sládek M., Sumová A.: The circadian system of patients with bipolar disorder differs in episodes of mania and depression. Bipolar Dis., 17: 303-3014, 2015

Nováková M., Nevšímalová S., Příhodová I., Sládek M., Sumová A.: Alteration of the circadian clock in children with Smith-Magenis syndrome. J. Clin. Endocrinol. Metab., 97(2): E312-8, 2012

Petrásek T., Prokopová I., Sládek M., Weissová K., Vojtěchová I., Bahník S., Zemanová A., Schonig K., Berger S., Tews B., Bartsch D., Schwab M.E., Sumova A., Stuchlik A.: Nogo-A-deficient transgenic rats show deficits in higher cignitive functions, decreased anxiety, and altered circadian activity patterns. Front. Behav. Neurosci. Vol. 8: 90, p. 1-15, 2014, doi: 10.3389/fnbeh.2014.00090

Petrásek T., Vojtěchová I., Lobellová V., Popelíková A., Janíková M., Brožka H., Houdek P., Sládek M.,Sumová A., Krištofiková Z., Valeš K., Stuchlík A.: McGill transgenic rat model of Alzheimer's disease displays cognitive and motor impairment, changes in anxiety and social behavior and altered circadian activity. Front. Aging Neurosci., 2018, Aug 28;10:250. doi: 10.3389/fnagi.2018.00250.

Supervisor:        Assoc. Prof. Dr. Alena Sumova, DSc.