The Notch pathway is one of the most important and well conserved signalling pathways that controls many different cell decisions and is associated with a number of diseases, including cancers. However, the consequences of activating Notch differ according to the cellular contexts. At one extreme Notch promotes proliferation and has been linked to tumor promotion, at the other hand it causes cell death and is considered as a tumour suppressor. In order to fully understand this apparent contradiction it is of vital importance to determine which factors are responsible for the modulation of Notch signalling pathway.
In our laboratory we investigate the nutritional/energetic state of a cell as potential regulator of Notch activity. We are particularly interested in the NAD+ and NADH levels that represent the cellular redox state. Using cultured cells as well as Drosophila model of Notch dependent cancer-like overgrowth we would like to determine how Notch signaling is influenced by changes in the cellular metabolic profile and what the molecular determinants are behind this regulation. We also investigate how some of the metabolic genes are under the transcriptional control by the Notch pathway, thus creating a regulatory loops. As a consequence we anticipate this will help to explain the differing responses to Notch activation and provide additional insight into Notch signaling under physiological conditions as well as in cancer.
Teaching at the Faculty of Sciences, Ceske Budejovice:
* Molecular biology
* Cell regulations and signalling
Bc., M.Sc. and Ph.D. positions available throughout the year.
List of people of Laboratory: Krejci Lab
List of publications of Laboratory: Krejci Lab