OUR Research

Exploring autophagosome maturation and fate

Utilizing Drosophila larval fat body as a model organism, our research is dedicated to investigating the fate of autophagosomes and autolysosomes. We aim to uncover new insights into the pathways and regulators governing autolysosome formation. Additionally, we explore the intriguing interplay between autophagy and endocytosis, a lesser-understood yet captivating field. Our work contributes to the ongoing quest to better understand the fundamental molecules driving these critical processes.

For further info see: PMID: 28704946, PMID: 28483915, PMID: 31682838

Figure: Wandering stage mosaic Drosophila fat bodies expressing 3xmCherry-Atg8a (red). hTfR-GFP positive cells (green) in addition express the desired RNAi construct and can be compared to in situ control cells (GFP negative), (which in this case decreases autolysosome size) . This and similar genetic toolkits enable us to do research at the frontier of our field.

Finding new regulators of endosome-lysosome pathways

Employing larval Garland nephrocytes as our primary model system, our research focuses on meticulously tracking the formation and maturation of endosomes. Building upon our previous work, where we highlighted the exceptional suitability of this cell type for studying endocytosis, we have successfully identified and characterized novel contributors to the endosome-to-lysosome pathways. Our ongoing mission is to deepen our understanding of this intricate process, delving deeper into the complexities of cellular biology.

For further info see: PMID: 28483915, PMID: 27253064, PMID: 31194677

Figure: In wild type controls (A), a layer of Rab7-positive late endosomes (green) is found under the peripheral Rab5 positive early endosomes (magenta). In contrast, larger Rab7 structures can be found in the cytoplasm of the indicated HOPS RNAi cells (B;C), suggesting a failure of late endosomal fusions.

Uncovering new pathways of Endocytosis and Autophagy

We study novel ways of vesicle trafficking events related to autophagy and endocytosis, including endosomal microautophagy (see image), autophagosome secretion, vesicle recycling, and extracellular vesicle release (this later is in collaboration with the group of Prof. Edit Buzás, SOTE).

Figure: Electron micrograph of a late endosome of a control nephrocyte show membrane invagination (blue arrow) indicating the uptake of cytosolic cargo (endosomal microautophagy).

Understanding tethering lock

We showed that loss of the SNARE protein Syx17 leads to the formation of stable, HOPS-dependent clusters of autophagosomes and lysosomes in Drosophila, which we call a “tethering lock.” This lock not only blocks fusion but also disrupts other trafficking pathways. Our findings suggest that the absence of a single SNARE can cause widespread cellular traffic jams—well beyond its direct fusion role. For further info see: PMID: 40479053

Figure: Electron micrograph showing autophagosome undergoing direct fusion with the lacunae plasmamembrane in Syx17, Plekhm1 double RNAi garland nephrocyte

Examining vesicle movement

Using fat cells and nephrocytes we discover new regulators of vesicle positioning in the endolysosomal and autolysosomal systems.

Figure: In wild type controls (A), a layer of Rab7-positive late endosomes (magenta) is found under the peripheral Rab5 positive early endosomes (green). In contrast expression of an RNAi (B) targeting a gene required for endosome motility completely disrupted this well organized pattern

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