Fachbereich 5


Navigation und Suche der Universität Osnabrück




SFB - Seminar 


"Unravelling the structure of toxic protein aggregates in situ”


27. Juni 2017 · 17:15 Uhr
Gebäude 35/E01
(Barbarastraße 11)

Dr. Ruben Fernandez Busnadiego (Institut für Biochemie, Max‐Planck‐Gesellschaft, München)


Protein aggregation is a hallmark of many neurodegenerative diseases, including Huntington’s, Parkinson’s and amyotrophic lateral sclerosis. However, the mechanisms linking aggregation to neurotoxicity remain poorly understood, partly because only limited information is available on the native structure of protein aggregates inside cells. We are addressing this challenge utilizing the latest developments in cryo-electron tomography (cryo-ET). We prepare thin lamellas of vitrified cells containing protein aggregates using cryo-focused ion beam, and subsequently image them in three dimensions by cryo-ET. This allows us to analyze aggregate structure within pristinely preserved cellular environments and at molecular resolution. Here I will discuss how our latest results shed new light into the cellular mechanisms of neurodegeneration

C. Ungermann

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Special SFB - Seminar 


“A novel mechanism of Leishmania donovani survival in human macrophages: Targeting Host Rab GTPase via small miRNAs”


28. Juni 2017 · 15 Uhr
Gebäude 35/E23-24
(Barbarastraße 11)

Dr. Jitender K. Verma, National Institute of Immunology, New Delhi - India



Leishmania donovani causes visceral leishmaniasis in human. These parasites are thought to reside and replicate in acidic phagolysosomal compartment in macrophages. But, how Leishmania survives in such a detrimental compartment in macrophages is not known. In contrast, most of the intracellular pathogens such as Salmonella, Mycobacterium, Listeria etc. avoid their trafficking to phagolysosomes in the host cells. In this study, we have established a novel mechanism of Leishmania survival inside human macrophages by targeting host Rab5a. Here, we report that Leishmania upregulates the expression of Rab5a, an early endosomal protein, by downregulating the expression of miR-494 in infected human macrophage. Subsequently, parasites recruit and retain Rab5a and EEA1 on their parasitophorous vacuole (PV) demonstrating that Leishmania resides in the early endosomal compartment and inhibits its transport to the lysosomes. Consequently, we also observed that recruitment of higher amounts of Rab5a leads to a block in transport of lysosomal markers like Lamp1 and Pro-CathepsinD (inactive) in early endosomes and thus results in their recruitment on Leishmania PV which led to the previous conclusion that Leishmania resides in the phagolysosomal compartment. Recruitment of Rab5a is essential for the parasite as its depletion via siRNA/miRNA significantly inhibits the survival of the parasites. Our studies provide the first mechanistic insights of parasite-mediated remodeling of endo-lysosomal trafficking and raise the possibility of using small molecules for future therapeutic intervention. 


C. Ungermann

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