What Makes Pathogens Successful?

pathogens
Variability of surface molecules, which are caused by differences in the chromatin structure, allow pathogens to evade the immune system. Shown are individual cells of trypanosomes (parasites causing human sleeping sickness).

A new EU-funded Innovative Training Network in the field of infection biology and chromatin biology will begin at LMU in November. The interdisciplinary ITN will explore the interactions between unicellular pathogens and their hosts at the single-cell level.

The Innovative Training Network (ITN) on “Cell2Cell Heterogeneity” is a program that is devoted to the question of why some pathogens within a population regularly succeed in establishing long-term infections, while others can be effectively controlled. The network will be coordinated jointly by Dr. Sigurd Braun (Physiological Chemistry, Faculty of Medicine) and Nicolai Siegel, Professor of Molecular Parasitology (Experimental Parasitology, Faculty of Veterinary Medicine). “The ITN will focus in particular on the role of epigenetic changes in chronic infections,” says Siegel. Using an interdisciplinary approach, the members of the network will study and compare pathogens at the single-cell level. In the long term, the insights obtained could contribute to the development of more effective therapies and new vaccines.

The strategy to be employed builds on recent advances in the scope and power of new technologies that are capable of characterizing biological states at the single-cell level. Thanks to these new methods, it is now known, for example, that differentiated cells of the same type can exhibit functional and biochemical heterogeneity, which is not attributable to genetic differences in their genomic DNA (i.e. mutations that alter nucleotide sequences), but to epigenetic modifications of the DNA-protein complexes (collectively called chromatin) in the cell nucleus. It is thought that this type of intercellular variability can be exploited by invasive unicellular parasites to enable them to adapt to the conditions within their host cells – and therefore contributes to the establishment of long-term, chronic infections. However, the very small size of the nucleus and the limited amount of genetic material present in unicellular parasites have so far hindered the use of single-cell technologies to probe the mechanisms underlying their interactions with host cells. “We hope to overcome this barrier and use these technologies to analyze the role of variations in chromatin structure at the level of single cells,” Braun explains. “LMU‘s Biomedical Center, where we are based, provides excellent opportunities for the implementation of this approach.“ The coordinators have chosen the pathogenic parasites Trypanosoma bruceiand Plasmodium falciparum – the organisms responsible for sleeping sickness and malaria, respectively – as their primary experimental models. In addition, other unicellular model systems that are better understood will also be incorporated into the work of the ITN. With the assured collaboration of specialists in research areas such as chromatin biology, parasitology, bioinformatics and high-throughput microscopy, Braun and Siegel hope that the resulting exchange of technological know-how will stimulate important advances in the analysis of infection biology.

Cell2Cell is being funded by the European Commission as part of its Framework Programme Horizon 2020, and will receive 3.9 million euros over 4 years. The project has been designated as a Marie Skłodowska-Curie Innovative Training Network (ITN) and, as such, it will place special emphasis on interdisciplinary training of doctoral researchers in a broad range of methods in academic and non-academic settings. In addition to LMU, ten other European institutions and biotech companies, as well as a further 9 partner organizations will participate in the venture. The Network will begin its work in November 2019.