Current research interest

Our laboratory addresses the biological fundamental questions how DNA integrity is preserved in female germ cells and how DNA damage is connected to diseases such infertility, Huntington’s disease or cancer.

This research interest originates from existence of the two greatly distinct cell lines in animals, germ cells and somatic cells. They have significantly different demands for the genetic stability. The germ lines must ensure transmission of the genetic information to the offspring and must be very effective in the DNA integrity maintenance. In somatic cells, DNA repair is a compromise between growth speed, cancer risk and also the cost for DNA repair. Until now a great effort was put into the research of chromosome segregation in female meiosis. However, the correct chromosome segregation is only one part of protection of the genome integrity. Also DNA repair of lesions such as double and single strand DNA breaks, crosslink DNA and cell cycle checkpoint outside anaphase are clearly very important, but largely unknown in germ line.  DNA damage can arise from exogenous attacks such radiation but also from own basic metabolism (oxygen radicals) or DNA metabolism (replication, transcription).

The connection of DNA to cancer is well known. However neurological disorders, for example Huntington’s disease, are also associated with DNA damage and compromise DNA repair, although they have completely different impact for patients. Very interestingly, it is known from records that patients with Huntington’s disease have significantly lower cancer incidences. It provokes a question, how it is possible that DNA damage can lead to two completely different problems: cancer or neurodegeneration?

Research projects:

• chromosome dynamics and integrity in mammalian oocytes (mouse knock-out models)
• DNA damage checkpoints in primary noncancerous cells (mouse knock-out models)
• DNA damage response in Huntington’s disease (minipig transgenic model)

Live cell imaging gallery

Movie 1 – Mouse primary cell expressing H2B-mCHERRY (red) and PCNA-GFP (green). Punctuated green signal marks progression through S-phase. Note defective chromosome segregation in mitosis. 

Movie 2 – Mouse oocyte expressing H2B-mCHERRY (red) and MAP4-GFP (green) progresses through meiotic maturation. Spindle formation, chromosome segregation and 1^st polar body extrusion are visible.

Movie 3 – Mouse oocyte expressing H2B-mCHERRY (red) and MAP4-GFP (green) with chromosome alignment and chromosome segregation defects.