24 April

Thesis defense Elke Roovers: Germ plasm condensates and the PIWI pathway

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Elke Roovers from the group of René Ketting, a former research group of the Hubrecht Institute currently at the Institute of Molecular Biology in Mainz, Germany, successfully defended her thesis on the 24th of April. During her PhD, Roovers studied the two different processes important in the formation of the germ line: the PIWI pathway, important for the protection of the DNA in the germ cells, and the germ plasm, an aggregation of various molecules important for the establishment of the germ line. The mechanisms underlying control over aggregation of the germ plasm may prove important for the regulation of other types of aggregations, such as those involved in the development of neurologic diseases such as Alzheimer’s and Parkinson. Roovers work on these processes is described in her thesis “Germ plasm condensates and the PIWI pathway: maternal and zygotic elements that shape the germline”.

piRNA biogenesis

Protecting the DNA
The germ line, the cells that will form the reproductive cells, is established during early embryonic development and needs to be kept safe until reproduction occurs. Our DNA contains transposable elements, small pieces of DNA can move to another spot in the DNA, or be copied and then insert into the DNA at a random position. One can imagine that the insertion of a transposable element into a gene, or a region that regulates the activity of a gene, can be very harmful to the cell in which this occurs. For normal body cells, this only affects that specific cell and its potential offspring. However, when this occurs in the germ line, this will affect fertility and potentially the entire offspring of the individual. Therefore, a system is in place in the germ cells that blocks the transposable elements from moving around or being copied: the PIWI pathway (see Figure).

PIWI pathway
The PIWI pathway uses PIWI proteins, members of the Argonaute protein family involved in RNA silencing, and small RNAs, called piRNAs, to recognize and cleave the transcripts of transposable elements, which effectively makes them inactive. Roovers used the zebrafish to study the function of a specific gene involved in the PIWI pathway, TdrKH, and found that it is involved in the trimming of these piRNAs. The initial piRNAs that are formed are often too long for the PIWI protein to function and the TdrKH protein is involved in shortening the piRNAs to a compatible length. Although the PIWI pathway does not seem to play a very large role in the female germ cells of the mouse, an animal often used as a model for human development, Roovers’ research suggests that the PIWI pathway does play an important role in other mammals, such as cows, macaques and humans.

Germ plasm and neurologic diseases
Another focus of Roovers’ research was the formation of the germ plasm in zebrafish oocytes (see Figure). This germ plasm is passed on to some the daughter cells in the embryo that will specify as germ cells. The germ plasm is not surrounded by a membrane, but is an accumulation of certain proteins, RNAs and other molecules that do not mix with the surrounding cytoplasm, like a drop of oil in water. A protein involved in the formation of the germ plasm Bucky ball, contains a prion-like domain. Prions are proteins that can aggregate so strongly that they induce other proteins to aggregate as well, which can in certain circumstances result in a diminished cellular function or cell death, for instance in neurologic diseases such as Alzheimer’s and Parkinson. Therefore, studying how germ plasm dynamics are controlled may also elucidate how toxic aggregations involved in neurologic diseases are formed, but also how we could manipulate and potentially revert them.

Germ plasm formation in the zebrafish oocyte

New proteins
During her PhD, Roovers identified new proteins that interact with Bucky ball, one of the proteins involved in germ plasm formation. These proteins localize together with the Bucky ball protein in cell cultures and some of the identified proteins contain prion-like domains, suggesting that these proteins may play a role in the formation of the germ plasm, and maybe other aggregates as well.

 


Elke Roovers started out her PhD at the Hubrecht Institute in Utrecht in the group of René Ketting. When his research group moved to the Institute of Molecular Biology in Mainz, Roovers also moved to our neighbouring country to continue her research. Now that her PhD is finished, she will move back to the Hubrecht Institute to start a post-doc in the group of Kerstin Bartscherer, where she will study the basic mechanisms involved in regeneration. To this end she will be using the flatworm Schmidtea mediterranea for its amazing ability to regenerate its entire body from almost any piece of the original individual in just a few days.

 

 

René Ketting is a former group leader of the Hubrecht Institute and current group leader and Scientific Director at the Institute of Molecular Biology in Mainz – Germany, and professor at the Johannes Gutenberg University of Mainz.

Banner: Zebrafish germ plasm in the oocyte.