@article{ZimmermannSubotaBatrametal.2017, author = {Zimmermann, Henriette and Subota, Ines and Batram, Christopher and Kramer, Susanne and Janzen, Christian J. and Jones, Nicola G. and Engstler, Markus}, title = {A quorum sensing-independent path to stumpy development in Trypanosoma brucei}, series = {PLoS Pathogens}, volume = {13}, journal = {PLoS Pathogens}, number = {4}, doi = {10.1371/journal.ppat.1006324}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158230}, pages = {e1006324}, year = {2017}, abstract = {For persistent infections of the mammalian host, African trypanosomes limit their population size by quorum sensing of the parasite-excreted stumpy induction factor (SIF), which induces development to the tsetse-infective stumpy stage. We found that besides this cell density-dependent mechanism, there exists a second path to the stumpy stage that is linked to antigenic variation, the main instrument of parasite virulence. The expression of a second variant surface glycoprotein (VSG) leads to transcriptional attenuation of the VSG expression site (ES) and immediate development to tsetse fly infective stumpy parasites. This path is independent of SIF and solely controlled by the transcriptional status of the ES. In pleomorphic trypanosomes varying degrees of ES-attenuation result in phenotypic plasticity. While full ES-attenuation causes irreversible stumpy development, milder attenuation may open a time window for rescuing an unsuccessful antigenic switch, a scenario that so far has not been considered as important for parasite survival.}, language = {en} } @article{DejungSubotaBuceriusetal.2016, author = {Dejung, Mario and Subota, Ines and Bucerius, Ferdinand and Dindar, G{\"u}lcin and Freiwald, Anja and Engstler, Markus and Boshart, Michael and Butter, Falk and Janzen, Chistian J.}, title = {Quantitative proteomics uncovers novel factors involved in developmental differentiation of Trypanosoma brucei}, series = {PLoS Pathogens}, volume = {12}, journal = {PLoS Pathogens}, number = {2}, doi = {10.1371/journal.ppat.1005439}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146362}, pages = {e1005439}, year = {2016}, abstract = {Developmental differentiation is a universal biological process that allows cells to adapt to different environments to perform specific functions. African trypanosomes progress through a tightly regulated life cycle in order to survive in different host environments when they shuttle between an insect vector and a vertebrate host. Transcriptomics has been useful to gain insight into RNA changes during stage transitions; however, RNA levels are only a moderate proxy for protein abundance in trypanosomes. We quantified 4270 protein groups during stage differentiation from the mammalian-infective to the insect form and provide classification for their expression profiles during development. Our label-free quantitative proteomics study revealed previously unknown components of the differentiation machinery that are involved in essential biological processes such as signaling, posttranslational protein modifications, trafficking and nuclear transport. Furthermore, guided by our proteomic survey, we identified the cause of the previously observed differentiation impairment in the histone methyltransferase DOT1B knock-out strain as it is required for accurate karyokinesis in the first cell division during differentiation. This epigenetic regulator is likely involved in essential chromatin restructuring during developmental differentiation, which might also be important for differentiation in higher eukaryotic cells. Our proteome dataset will serve as a resource for detailed investigations of cell differentiation to shed more light on the molecular mechanisms of this process in trypanosomes and other eukaryotes.}, language = {en} }