Molecular-biological studies about the fate of micronuclei: underlying mechanisms and toxicological relevance
Project management at the University of Würzburg:
Different types of mutations play a major role in carcinogenesis, e. g. chromosomal mutations, which are characterized by modifications of the chromosome structure. One form of manifested chromosomal mutations are so-called micronuclei that are formed from chromosomal fragments or missegregated chromosomes. The formation of micronuclei has been investigated thoroughly and the underlying mechanisms are well understood. However, it is still unclear whether micronuclei persist within the cell or whether there are any specific mechanisms of elimination. In principle, there could be four possibilities: persistence in the cell, degradation, expulsion from the cell or reintegration into the main nucleus. In this project, the fate of micronuclei and the relevance for the whole cell shall be addressed systematically for the first time in order to identify and to characterize the underlying mechanisms.
In a first step, the conditions under which micronuclei can be eliminated, will be identified using live imaging. The cells will be followed for several cell cycle generations. On this basis, the molecular processes leading to certain fates of micronuclei will be investigated. To this end, protein expression will be quantified on the cellular level and protein localisation and its alterations will be assessed. Finally it will be studied whether these phenomena also occur in the human organism. Samples from patients receiving radiation therapy will be extracted and analysed to determine the fate of micronuclei.
All in all, this research project aims at demonstrating the conditions under which chromosomal mutations in the form of micronuclei persist or can be eliminated. The underlying mechanisms will be investigated and this knowledge will provide deeper understanding of these processes that are associated with the influence of various agents on carcinogenesis.
Projekt period: from 10.2017 to 09.2019
DFG ,Granting date: 09.11.2016