Gerald SPAETH

Information

Scientific interests and projects

The unit ‘Molecular Parasitolgy and Signaling’ conducts multidisciplinary and internationally highly visible research on Leishmania/macrophage interaction and co-evolution. Our program analyses Leishmania and macrophage regulatory pathways implicated in intracellular parasite development and subversion of host cell functions that qualify as novel drug targets. We will pursue three main axes as part of the ParFrap consortium:

Axis 1 investigates mechanisms of Leishmania differentiation and evolutionary adaptation by conducting systems level and comparative genomics analyses of hamster-derived parasites and clinical isolates with the aim to identify genetic loci that are linked to Leishmania fitness gain in culture and in infected animals;

Axis 2 analyses the signalling role of the Leishmania ecto-kinase CK1.2 and its role in subversion of host cell immune signalling, with the aim to target its exosomal release for anti-leishmanial therapy;

Axis 3 studies mechanisms of Leishmania host subversion using immunological, pharmacological and systems-level investigations, with the aims to (i) discover host-directed, anti-leishmanial hits and (ii) study the impact of intracellular Leishmania infection on macrophage epigenetic regulation, phenotype and functions.

Together these three axes provide important added value to the main ParaFrap scientific work packages, including WP1 on post genomic data exploration (Axes 1 – 3), WP2 on mechanisms of pathogenesis and anti-parasite immunity (Axes 2 and 3), WP3 on parasite molecular and cellular biology (Axes 1 and 3), and WP4 on development of new intervention strategies against parasitic pathogens (Axes 2 and 3).

1. Bussotti G et al. and Späth GF. Leishmania Genome Dynamics during Environmental Adaptation Reveal Strain-Specific Differences in Gene CNV, Karyotype Instability, and Telomeric Amplification. MBio. 2018 doi: 10.1128/mBio.01399-18

2. Prieto Barja P et al. and Späth GF. Haplotype selection as an adaptive mechanism in the protozoan pathogen Leishmania donovani. Nature Ecol Evol, 2017. doi: 10.1038/s41559-017-0361-x

3. Drini S et al., and Späth GF. Species- and Strain-Specific Adaptation of the HSP70 Super Family in Pathogenic Trypanosomatids. Genome Biol Evol. 2016. 10.1093/gbe/evw140

4. Cayla M et al. and Späth GF. Transgenic analysis of the Leishmania MAP kinase MPK10 reveals an auto-inhibitory mechanism crucial for stage-regulated activity and parasite viability. PLoS Path. 2014 10.1371/journal.ppat.1004347

5. Dacher M et al. and Späth GF. Probing druggability and biological function of essential proteins in Leishmania combining facilitated null mutant and plasmid shuffle analyses. Mol Microbiol. 2014 10.1111/mmi.12648