Project 5
Temperature adaptation of di- and monoxenic trypanosomatids
Supervisors:
Ute A. Hellmich (main supervisor)
Biostructural Interactions Group, Friedrich-Schiller University Jena
Marta Bogacz (co-supervisor)
Biostructural Interactions Group, Friedrich-Schiller University Jena
Martin Kaltenpoth (co-supervisor)
Department of Insect Symbiosis, Max Planck Institute for Chemical Ecology
Tobias Engl, MPI-CE (co-supervisor)
Department of Insect Symbiosis, Max Planck Institute for Chemical Ecology
Background:
Trypanosomatids are unicellular flagellate protists. Dixenous species (Trypanosoma brucei, T. cruzi) alternate between insect and mammalian hosts, while monoxenous species (Leptomonas) infect a single insect host. In T. brucei, the causing agent of sleeping sickness, we have characterized several putative drug targets and, more recently, molecular determinants of host-dependent heat-stress adaptation. We found that responses to temperature and redox stress are closely intertwined.
Insects are poikilotherms, so their parasites face wide, fluctuating temperatures. We ask how monoxenous trypanosomatids such as Leptomonas pyrrhocoris (a parasite of Pyrrhocoridae) cope with these changes, and whether they use conserved temperature/redox sensors like those of dixenous species. Comparative transcriptomics and metabolomics under heat stress may also reveal further, uncharacterized players. Finally, heat and redox stress strain energy metabolism and redox-active metal homeostasis in both parasite and host, and the largely uncharacterized ion channels involved may shape the host-parasite relationship under normal and stress conditions.
Project description:
This project will characterize temperature sensing and host adaptation in Leptomonas and compare it with dixenous trypanosomatids. It spans molecules (protein biochemistry, structural biology), cells (knock-outs/knock-ins, redox and temperature stress assays in T. brucei and L. pyrrhocoris, high-resolution microscopy) and organisms (insect host assays, omics under stress), and aims to identify determinants of parasite-host co-evolution. It builds on our groups’ expertise in structural biology and biophysics of trypanosomatid proteins, and in insect infection and symbiont biology.
Candidate profile:
MSc in biochemistry, molecular or cell biology, parasitology or a related field. Experience in protein biochemistry or parasite/cell culture is desirable, as is interest in biophysical methods (NMR, mass spectrometry) and insect-microbe interactions. Basic bioinformatics skills for proteomics data are a plus. We seek a curious, independent and collaborative person with good written and spoken English and a passion for interdisciplinary research.
Reading:
Kraeva et al (2015) Leptomonas seymouri: Adaptations to the Dixenous Life Cycle Analyzed by Genome Sequencing, Transcriptome Profiling and Co-infection with Leishmania donovani. Plos Pathogens, https://doi.org/10.1371/journal.ppat.1005127
Onchuru et al (2018) The cotton stainer's gut microbiota suppresses infection of a cotransmitted trypanosomatid parasite. Mol Ecol. doi: 10.1111/mec.14788.
Teixeira et al (2019) Chaperone activation and client binding of a 2-cysteine peroxiredoxin. Nature Commun., doi: s41467-019-08565-8
Bogacz et al (2020) The mitochondrial peroxiredoxin displays distinct roles in different developmental stages of African trypanosomes. Redox Biol., doi: 10.1016/j.redox.2020.101547
Schwegler et al (2026) Inhibitor fluorination pattern modulates protein surface dynamics and chemically induced dimerization. Chem. Sci, DOI: 10.1039/d6sc05625c