Dr Nicola Silva from the Department of Biology at the Faculty of Medicine of Masaryk University discovered a previously undescribed protein that stimulates the proper chromosome pairing and its stabilization while researching the processes behind the formation of reproductive cells. The protein, called BRA-2, is also the first one in which scientists have demonstrated that it is an essential factor for the formation of the so-called synaptonemal complex – a zipper-like protein structure that connects a pair of chromosomes, allowing for the physical exchange of DNA segments, i.e. genetic information, between them. The study on the new protein was published in the scientific journal Nature Communications.
“Moving chromosomes have to find each other in the vast and fairly messy environment of the cell nucleus – the one from the father has to connect with the one from the mother to form a homologous pair. Once the right ones meet, a spark jumps between them, so to speak, and the synaptonemal complex starts to form and connects them. BRA-2 stimulates this formation – we could basically say it gives the chromosomes permission to connect by confirming that they are truly homologous," explains Nicola Silva. He and his colleagues also found that if the BRA-2 protein is missing, only a very short stretch of the complex forms between chromosomes, often none at all, resulting in the production of defective reproductive cells.
BRA-2 is important for several reasons, one of which is that during the formation of the synaptonemal complex, it can partially substitute for the function of a previously described protein, HIM-17. It was also thanks to HIM-17 – and to the CRISPR method – that scientists discovered BRA-2. Using these “genetic scissors,” they create “protein baits” that bind other potentially unknown proteins. "We enrich the selected protein, in this case HIM-17, and when we pull this protein down, we can distinguish our tagged protein and then analyze the binding partners using mass spectrometry,” says Silva, describing a commonly used method.
According to him, a key prerequisite for new discoveries is “having high quality pulldowns, for which high purity of protein extracts from meiotic cells is key”, which the Brno lab secures thanks to years of experience with the model organism Caenorhabditis elegans. These are approximately one-millimeter-long worms that are highly suitable for experiments, and research on them has already earned several scientists the Nobel Prize, most recently in 2024. Compared to mice, working with them is faster and less expensive. And above all: “The development of reproductive cells is absolutely great to study in them, because even though it’s a simple organism, it includes all the signaling and regulatory pathways that play a role in humans too,” explains the Italy-born researcher settled in South Moravia.