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Our research focuses on three main topics: ciliogenesis, parasitology, and membrane trafficking. Cilia and flagella are conserved organelles in most eukaryotes, which have attracted much attention in recent years because of their role in the transduction of extracellular signals and their association with an expanding number of human disorders. We have also been working on multiple large cytoskeletal proteins in human parasites including Trypanosoma brucei, Toxoplasma gondii, and Plasmodium. Membrane trafficking has been a long-lasting interest of us, for which we have focused mainly on vesicle targeting and membrane fusion.
The approaches we use to address the scientific questions include structural biology, biochemistry, biophysics, and molecular biology. We mainly use X-ray crystallography to determine the 3D structures of target macromolecules, which is complemented by the other two state-of-the-art methods, NMR spectroscopy and electron microscopy (EM). We also routinely use static/dynamic light scattering (SLS/DLS), circular dichroism (CD), isothermal titration calorimetry (ITC) in our studies. Our structural studies are often coupled with site-directed mutagenesis, in vitro biochemical experiments, and in vivo assays to validate our mechanistic hypotheses.
Gang Dong studied plant pathology in college and biophysics as a master’s student. After obtaining his PhD in 2002 from the University of Texas at Austin, he moved to work with Karin M. Reinisch at the Yale School of Medicine as a postdoc fellow working on membrane trafficking and antigen presentation. He was recruited to the Medical University of Vienna in 2008 to set up his own research group.
We have reported the crystal structure of the t-SNARE Sso2 in complex with Sec3, a component of the exocyst complex that serves as a vesicle tether at the plasma membrane. Our work provides a mechanistic explanation for the initial step of vesicle fusion (Yue P*, Zhang Y* et al. 2017, Nat. Commun.).
SET-domain lysine methyltransferases (KMTs) play key roles in regulation of gene expression in eukaryotes. We recently reported the structure of a novel dimeric KMT, the AKMT protein from the human parasite Toxoplasma gondii. Our work reveals that AKMT is the founding member of a new subclass of KMT and forms the basis for future therapeutic interventions (Pivovarova Y et al. 2018, J. Mol. Biol.).
Trypanosoma brucei is the causative agent of sleeping sickness that threatens millions of African people. We have unraveled the architecture and assembly of a filamentous cytoskeletal protein named BILBO1, which acts as the scaffold of the flagellar pocket collar of T. brucei and is indispensable to its survival and pathogenicity (Vidilaseris K et al. 2020, J. Biol. Chem.; Vidilaseris K et al. 2014, J. Biol. Chem.).
Polo-like kinase 4 (Plk4) has emerged as a master regulator of centriole duplication. We have reported crystal structures of the cryptic polo box of both Drosophila Plk4 and its C. elegans homolog ZYG-1. Our findings shed light on the conserved molecular mechanism underlying the recruitment of Plk4 and ZYG-1 to the nascent centriole (Shimanovskaya E et al. 2014, Structure).
Centrioles play essential roles in both centrosome formation and cilium biogenesis. We have carried out structural studies on SAS-5 and SAS-6, two of the five core centriolar proteins. Our work uncovers the specific interaction between them and suggests a mechanism for them to cooperatively facilitate the correct assembly of the 9-fold symmetric centriole (Qiao R et al. 2012, EMBO J.).
Structure of a Novel Dimeric SET Domain Methyltransferase that Regulates Cell Motility.
Pivovarova, Yulia; Liu, Jun; Lesigang, Johannes; Koldyka, Oliver; Rauschmeier, Rene; Hu, Ke; Dong, Gang
Sec3 promotes the initial binary t-SNARE complex assembly and membrane fusion.
Yue, Peng; Zhang, Yubo; Mei, Kunrong; Wang, Shaoxiao; Lesigang, Johannes; Zhu, Yueyao; Dong, Gang; Guo, Wei
Structure of the C. elegans ZYG-1 Cryptic Polo Box Suggests a Conserved Mechanism for Centriolar Docking of Plk4 Kinases.
Shimanovskaya, Ekaterina; Viscardi, Valeria; Lesigang, Johannes; Lettman, Molly M; Qiao, Renping; Svergun, Dmitri I; Round, Adam; Oegema, Karen; Dong, Gang
Project title: "Structural basis of tRNA synthetase-based selfish killer" (P 34880)
A new grant was freshly approved by the FWF on 10 May, 2021! This grant (Sum: 603,960.00 EUR) will support the collaborative work between Alejandro Burga’s group (IMBA) and us on eukayrotic Selfish Elements, which underlie numerous cases of hybrid dysgenesis, sterility and genetic incompatibilities in nature. We will use our complementary expertise in genetics and structural biology to dissect the molecular mechanism of a set of selfish elements in the nematodes C. elegans and C. tropicalis.
Duration: 2021 - 2025.
Project title: "Mechanism of infectivity acquisition in African trypanosomes" (2 R01 AI110325-06)
A newly approved NIH-R01 grant ($345,724.00; total: $2,311,805.00) to support our collaborative work with Dr. Christian Tschudi's group at the Yale School of Medicine to unveil the molecular mechanism of the infectivity acquisition in African Trypanosomes.. Our complementary expertise will provide unique opportunities for us to illuminate the developmental program leading from non-infective procyclics to infectious metacyclics, a crucial process in the T. brucei life cycle.
Duration: 01 Mar, 2019 - 29 Feb, 2024.
Project title: "Why and how trypanosomes build a flagellar pocket collar" (I 4960-B)
In collaborataion with Dr. Melanie Bonhivers from the University of Bordeaux and co-funded by the FWF (Austria) and the ANR (France). The grant (Sum: 705,485.70 EUR) will support our joint effort to study the flagellar pocket collar (FPC) of the human parasite Trypanosoma brucei. We aim to explain how a new FPC is formed, why it is essential, what polymers/proteins are needed, and how they interact.
Duration: 01 Oct, 2020 - 30 Sept, 2024.
The Group Dong participated in and was one of the seven full members of the Doctoral Program "Integrative Structural Biology" (W-1258), which was reviewed and funded by the Austrian Science Fund FWF.
Duration: 01 Jan, 2016 - 30 June, 2020.
Project title: “Structural Characterization of ZYG-1 in Centriole Assembly" (P 28231)”
Duration: 01 July, 2015 - 30 June, 2020.
Project title: “Structural studies of the Trypanosoma brucei protein TbBILBO1" (P 24383-B21)
Duration: 01 May, 2012 - 30 Apr, 2016.
Project title: “Structural Studies of the Intraflagellar Transport Complexes" (P 23440-B20)
Duration: 01 Apr, 2011 - 31 Oct, 2015.
Project title: "Towards sustainable food and bioenergy security for society: Establishing an academic compound screening platform in Vienna to characterize and modulate Strigolactone synthesis in plants" (WWTF 2009) Role: Research Partner (PI: Dr. T. Sieberer). Duration: 2011 - 2014.