Bonn researchers use nanobodies to elucidate pore formation by gasdermin D in cell membranesThe formation of pores by a particular protein, gasdermin D, plays a key role in inflammatory reactions. During its activation, an inhibitory part is split off. More than 30 of the remaining protein fragments then combine to form large pores in the cell membrane, which allow the release of inflammatory messengers. As methods for studying these processes in living cells have so far been inadequate, the sequence of oligomerization, pore formation and membrane incorporation has remained unclear. An international research team led by the University Hospital Bonn (UKB) and the University of Bonn has succeeded in answering this question with the help of antibody fragments, so-called nanobodies, which they have identified. They hope that this will lead to potential therapeutic applications. Their results have now been published in the journal “Nature Communications”. 

Whether or not a person becomes seriously ill with COVID-19 depends, among other things, on genetic factors. With this in mind, researchers from the University Hospital Bonn (UKB) and the University of Bonn, in cooperation with other research teams from Germany, the Netherlands, Spain and Italy, investigated a particularly large group of affected individuals. They confirmed the central and already known role of the TLR7 gene in severe courses of the disease in men, but were also able to find evidence for a contribution of the gene in women. In addition, they were able to show that genetic changes in three other genes of the innate immune system contribute to severe COVID-19. The results have now been published in the journal “Human Genetics and Genomics Advances”.

Monocytes, a special type of white blood cell, secrete cytokines as inflammatory messengers that are crucial for an appropriate immune response. Researchers at the University Hospital Bonn (UKB) and the University of Bonn have now discovered that platelets, also known as thrombocytes, communicate with monocytes and increase their inflammatory capacity. By understanding the platelet-monocyte interaction, they hope to improve the treatment of immune disorders and associated diseases. The results of the study have now been published in the renowned journal “EMBO Molecular Medicine” and will be featured on the cover of August issue.

Recent reports suggest that somatic cell-derived induced neurons (iNs), but not induced pluripotent stem cell (iPSC)-derived neurons largely preserve age-associated traits such as age-specific DNA methylation patterns, transcriptomic aging signatures and nuclear lamina-associated changes.

The mechanisms of NLRP3 activation are still poorly understood. Jonathan Schmid-Burgk and colleagues present new data on the identification of NEK7, which specifically functions upstream of NLRP3 activation. NEK7 was identified in an unbiased genetic screening approach, which employed the CRISPR technology to identify macrophages that were rendered defective in NLRP3 signal transduction.

Dowling-Degos disease is a hereditary pigmentation disorder that generally progresses harmlessly. However, some of those affected also develop severe skin inflammation. 

An international research team led by the University of Bonn has identified and further developed novel antibody fragments against the SARS coronavirus-2. These “nanobodies” are much smaller than the classic antibodies, for example. They therefore penetrate the tissue better and can be produced more easily in larger quantities. The researchers at the University Hospital Bonn have also combined the nanobodies into potentially particularly effective molecules. These attack different parts of the virus simultaneously. The approach could prevent the pathogen from evading the active agent through mutations. The results are published in the journal Science.

Children born to obese mothers are at higher risk of developing metabolic disorders, even if they follow a healthy diet themselves. A new study from the University of Bonn offers an explanation for this phenomenon. In obese mice, certain cells in the embryo’s liver are reprogrammed during pregnancy. This leads to long-term changes in the offspring’s metabolism. The researchers believe that these findings could also be relevant for humans. The study has now been published in the journal Nature.