Lehrstuhl für Zell- und Entwicklungsbiologie

engstler lab

We study the adaptive and dynamic pleomorphism of parasites on the molecular, cellular and organismal level

Research synopsis

Yes, it’s true. We work on many, at first sight unrelated topics. What is the connection between antigenic variation and parasite motility? How is quorum sensing in trypanosomes related to tsetse biology? And how are these topics linked to the dynamics and structure of the cell surface?

The common denominator of all our interests is the evolutionary adaptation of the African trypanosome to host and vector. We have shown that incessant motility is essential for removing host antibodies from the parasite’s cell surface. For this to work, the structure of the main surface proteins has been shaped for high mobility, even at the molecular crowding threshold. We have shown that endocytosis in trypanosomes is very fast, which allows rapid uptake and destruction of immune effector molecules. Obviously, antibody clearance is only one line of host defence; antigenic variation is the major one. We have shown that VSG switching and trypanosome development are linked processes. The VSG expression site is the virulence hub that not only controls antigenic variation but can also trigger developmental progress - in the absence of the quorum sensing molecule SIF. We show that the plasticity of the tyrpanosome's life cycle has been underestimated, as the cell cycle arrrested stumpy stage is not required for developemental progression. We developed artficial skin and discovered that tsetse-fly transmitted parasites devevlop to an undiscovered life cycle stage, the skin tissue forms.

It is the streamlined nature of parasites that makes it very difficult not to get scientifically diverted - from time to time. All cellular and phsiycal features of trypanosomes are reflective of their parasitic life style: they thrive in the mammalian host and prosper in the tsetse fly. You have to be quite flexible to master such a life.

And it needs an interdisciplinary team to (sometimes) tame the parasite.

Selected publications

Subcellular dynamics in unicellular parasites. Müller T, Krüger T, Engstler M. Trends Parasitol. 2025 Mar;41(3):222-234. doi: 10.1016/j.pt.2025.01.007. Epub 2025 Feb 10. PMID: 39933989.

ThirdPeak is a flexible tool designed for the robust analysis of two- and three-dimensional tracking data. Müller T, Meiser E, Engstler M. Commun Biol. 2024 Dec 20;7(1):1683. doi: 10.1038/s42003-024-07378-w. PMID: 39702822; PMCID: PMC11659616.

The actomyosin system is essential for the integrity of the endosomal system in bloodstream form Trypanosoma brucei. Link F, Jung S, Malzer X, Zierhut F, Konle A, Borges A, Batters C, Weiland M, Poellmann M, Nguyen AB, Kullmann J, Veigel C, Engstler M, Morriswood B. Elife. 2024 Nov 21;13:RP96953. doi: 10.7554/eLife.96953. PMID: 39570285; PMCID: PMC11581428.

The release of host-derived antibodies bound to the variant surface glycoprotein (VSG) of Trypanosoma brucei cannot be explained by pH-dependent conformational changes of the VSG dimer. Eirich P, Nesterov P, Shityakov S, Skorb EV, Sander B, Broscheit J, Dandekar T, Jones NG, Engstler M. Open Res Eur. 2024 Apr 24;4:87. doi: 10.12688/openreseurope.16783.1. PMID: 38903703; PMCID: PMC11187536.

Continuous endosomes form functional subdomains and orchestrate rapid membrane trafficking in trypanosomes. Link F, Borges A, Karo O, Jungblut M, Müller T, Meyer-Natus E, Krüger T, Sachs S, Jones NG, Morphew M, Sauer M, Stigloher C, McIntosh JR, Engstler M. Elife. 2024 Apr 15;12:RP91194. doi: 10.7554/eLife.91194. PMID: 38619530; PMCID: PMC11018342.

Vector-borne Trypanosoma brucei parasites develop in artificial human skin and persist as skin tissue forms. Reuter C, Hauf L, Imdahl F, Sen R, Vafadarnejad E, Fey P, Finger T, Jones NG, Walles H, Barquist L, Saliba AE, Groeber-Becker F, Engstler M. Nat Commun. 2023 Nov 23;14(1):7660. doi: 10.1038/s41467-023-43437-2. PMID: 37996412; PMCID: PMC10667367.

Gene editing and scalable functional genomic screening in Leishmania species using the CRISPR/Cas9 cytosine base editor toolbox LeishBASEedit. Engstler M, Beneke T. Elife. 2023 May 24;12:e85605. doi: 10.7554/eLife.85605. PMID: 37222701; PMCID: PMC10208639.

The Intracellular Amastigote of Trypanosoma cruzi Maintains an Actively Beating Flagellum. Won MM, Krüger T, Engstler M, Burleigh BA. mBio. 2023 Apr 25;14(2):e0355622. doi: 10.1128/mbio.03556-22. Epub 2023 Feb 22. PMID: 36840555; PMCID: PMC10128032.

Nanobody-mediated macromolecular crowding induces membrane fission and remodeling in the African trypanosome.
Hempelmann A, Hartleb L, van Straaten M, Hashemi H, Zeelen JP, Bongers K, Papavasiliou FN, Engstler M, Stebbins CE, Jones NG.
Cell Rep. 2021 Nov 2;37(5):109923. doi: 10.1016/j.celrep.2021.109923. PMID: 34731611

Unexpected plasticity in the life cycle of Trypanosoma brucei.
Schuster S, Lisack J, Subota I, Zimmermann H, Reuter C, Mueller T, Morriswood B, Engstler M.
Elife. 2021 Aug 6;10:e66028. doi: 10.7554/eLife.66028. PMID: 34355698

Single-cell motile behaviour of [Formula: see text] in thin-layered fluid collectives.
Krüger T, Maus K, Kreß V, Meyer-Natus E, Engstler M.
Eur Phys J E Soft Matter. 2021 Mar 23;44(3):37. doi: 10.1140/epje/s10189-021-00052-7. PMID: 33755816

RESEARCH TOPICS

African sleeping sickness

Human trypanosomiasis and its animal form Nagana are a prime examples for the One Health concept

Antigenic variation

The exchange of surface coats is the phenotypic hallmark of antigenic variation. But in fact, this is just the tip of an iceberg

Host skin infection

Trypanosomes enter the mammalian host with the bite of a hungry tsetse.

What do they do in the skin?

Parasite Motility

The trypanosome flagellum always beats. Motion is essential for immune escape and tsetse passage - and it is a very complex business

Quorum Sensing

Trypanosomes limit the population size in the host by quorum sensing. What is the trigger?

Surface Coat Dynamics

The trypanosome VSG layer is a good model for fundamental studies on protein mobility.

Structure of the cell surface

The structure of the trypanosome surface coat is much more dynamic and flexible than generally assumed

Trafficking of GPI-proteins

Lipid-anchoring has implications on the sorting and trafficking of cell surface coat molecules

Tsetse biology and physics

The tsetse fly provides a self-contained environment for adaptive morphogenesis of trypanosome microswimmers

PEOPLE

Tim Krüger