What makes a successful pathogen – Understanding the impact of cell-to-cell heterogeneity in chromatin structure on infection and adaptation

“Cell2Cell Heterogeneity” is a European training network for doctoral students with focus on the question of why individual pathogens within a population succeed in establishing long-term infections, while others are effectively eliminated by the host. The network will be coordinated by Dr. Sigurd Braun, independent group leader at the Department of Physiological Chemistry (Faculty of Medicine), and Nicolai Siegel, Professor of Molecular Parasitology (Experimental Parasitology, Faculty of Veterinary Medicine), who both have their research groups at the BMC. Using an interdisciplinary approach, the members of the network will analyze dynamics and heterogeneity in the chromatin structure of pathogens and other unicellular organisms, which are linked to infection and environmental adaptation, at the single-cell level. In the long term, the insights obtained could contribute to the development of more effective therapies and new vaccines.
Recent technology advances have started to revolutionize modern biology, making it now possible to analyze gene expression activity or genome organization of a single cell. These studies revealed a non-anticipated functional and biochemical heterogeneity within cell populations of the same cell type or tissue. Often, these phenotypic variations have their origin in different modifications and organization of nuclear DNA-protein complexes commonly known as chromatin. For instance, changes in the chromosomal organization of genes cause variability of surface proteins in Trypanosoma brucei and allow this pathogenic parasite to evade recognition by the immune system of the host. However, the very small size of the nucleus and the limited amount of genetic material present in unicellular organisms (such as trypanosomes or other protozoan parasites) have so far hindered the use of single-cell technologies to probe the underlying mechanisms that cause changes in chromatin organization. To overcome these barriers, Cell2Cell has brought together experts from different research areas to enable the transfer of a broad set of methodologies from chromatin biology, parasitology, bioinformatics and high-throughput microscopy. In addition, besides investigating the pathogenic parasites Trypanosoma brucei and Plasmodium falciparum (responsible for sleeping sickness and malaria, respectively), Cell2Cell will exploit the vast knowledge and technical advances established in various yeast model systems.
Cell2Cell will be 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 the 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 and will soon start to advertise the 15 available PhD positions.