Moritz Treeck Lab

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Moritz Treeck

Group Leader

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Cell Biology of Host – Pathogen Interaction

Moritz Treeck’s laboratory focuses on understanding how parasites like Plasmodium falciparum (which causes malaria) and Toxoplasma gondii interact with and manipulate their host cells.

The team uses advanced techniques such as mass spectrometry and CRISPR-Cas9 gene editing to study how these parasites modify host cells to evade the immune system and survive. Their research aims to uncover the mechanisms parasites use to sense their environment, respond to changes like fever, and reprogram host cells. By investigating these host-parasite interactions, the Treeck Lab hopes to lay the groundwork for developing new therapeutic strategies against these infectious diseases. Their work spans various stages of parasite life cycles and employs innovative methods to identify and characterize parasite proteins that are crucial for infection and survival.

Funders

Parasites are subversive; they bend their environment to their own ends. Plasmodium falciparum and Toxoplasma gondii are two of a large group of single-celled parasites (the Apicomplexa) that invade host cells and hijack the normal biology of those cells to support their own development.

In the case of Plasmodium. falciparum, the parasite that causes malaria, this has severe consequences: more than 400,000 people die of malaria each year, and more than 200 million people are infected. Despite being so widespread, Plasmodium falciparum is a specialist: it has very limited host cell type and species specificity.

Toxoplasma gondii, in contrast, is a generalist: it can infect any nucleated cell of any warm-blooded species – including humans. It is estimated that about 30% of the world’s population is infected with Toxoplasma. In most people, this infection is dormant because it is controlled by the immune system, but it is never completely cleared. In pregnant or immune-suppressed individuals, however, Toxoplasma can become a real threat: it can cause severe problems in developing foetuses, and untreated infection in immune-compromised individuals can result in severe eye and brain damage, or even death.

These two parasites live in very different biological niches, but immune evasion, host cell remodelling, and adaptions to enable transmission between hosts are key to both of their parasitic lifestyles. Our main aim is to determine how the parasites remodel their hosts to for survival, immune evasion, and dissemination. The key tools we use for this are quantitative mass spectrometry, which allows us to interrogate protein interactions and modifications that underpin these processes, and CRISPR-Cas9 based knockout screening, to assess the functional contribution of hundreds of different proteins at the same time. Together with other biochemical, cell biological, and genetic tools, these technologies allow us to uncover exciting and novel biology to build the basis for future therapeutic strategies.

How does Toxoplasma subvert its host cell and host to provide a favourable environment?
How does an expanded and exported family of protein kinases of the malaria causing parasite Plasmodium falciparum contribute to increased virulence in humans.
Development of novel technologies to advance the study of host-pathogen interactions in Plasmodium and Toxoplasma.

F. Torelli, D. M. da Fonseca, S. W. Butterworth, J. C. Young, M. Treeck (2024). Paracrine rescue of MYR1-deficient Toxoplasma gondii mutants reveals limitations of pooled in vivo CRISPR screens. eLife 13: e102592. https://doi.org/10.7554/eLife.102592.

F. Torelli, et al. (2024). In vivo CRISPR screens identify GRA12 as a transcendent secreted virulence factor across Toxoplasma gondii strains and mouse subspecies. bioRxiv, 2024.09.10.611481. https://doi.org/10.1101/2024.09.10.611481. (Accepted, Nature Communications).

H. Belda, et al. (2024). Evolution and inhibition of the FIKK effector kinase family in Plasmodium falciparum. bioRxiv, 2024.02.22.581535. https://doi.org/10.1101/2024.02.22.581535. (Accepted, Nature Microbiology).

E. J. Lockyer, et al. (2023). A heterotrimeric complex of Toxoplasma proteins promotes parasite survival in interferon gamma-stimulated human cells. PLoS Biology 21: e3002202. https://doi.org/10.1371/journal.pbio.3002202.

H. Davies, H. Belda, M. Broncel, J. Dalimot, M. Treeck (2023). PerTurboID, a targeted in situ method reveals the impact of kinase deletion on its local protein environment in the cytoadhesion complex of malaria-causing parasites. eLife12: e86367. https://doi.org/10.7554/eLife.86367.

S. Butterworth, et al. (2023). High-throughput identification of Toxoplasma gondii effector proteins that target host cell transcription. Cell Host & Microbe 31: 1748–1762.e8. https://doi.org/10.1016/j.chom.2023.09.003.

S. D. Nofal, et al. (2022). A positive feedback loop mediates crosstalk between calcium, cyclic nucleotide, and lipid signaling in calcium-induced Toxoplasma gondii egress. PLoS Pathogens 18: e1010901. https://doi.org/10.1371/journal.ppat.1010901.

H. Davies, et al. (2020). An exported kinase family mediates species-specific erythrocyte remodeling and virulence in human malaria. Nature Microbiology 5: 848–863. https://doi.org/10.1038/s41564-020-0702-4.

M. Broncel, et al. (2020). Profiling of myristoylation in Toxoplasma gondii reveals an N-myristoylated protein important for host cell penetration. eLife 9: e57861. https://doi.org/10.7554/eLife.57861.

M. Tiburcio, et al. (2019). A novel tool for the generation of conditional knockouts to study gene function across the Plasmodium falciparum life cycle. mBio 10: e01170-19. https://doi.org/10.1128/mBio.01170-19.

A complete list of publications can be found here.