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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, et al, Nature Communications, 2017).
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.
Trypanosoma brucei is the causative agent of sleeping sickness threatening 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 andP is indispensable to its survival and pathogenicity.
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.
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.
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: "Why and how trypanosomes build a flagellar pocket collar"
In collaborataion with Dr. Melanie Bonhivers from the University of Bordeaux and co-funded by the FWF (Austria) and the ANR (France). The grant is endowed with a total of 705,485.70 EUR (404,289.90 EUR for us) and will support our joint effort to study the flagellar pocket collar (FPC) of the human parasite Trypanosoma brucei, which causes sleeping sickness, a disease that threatens millions of people in sub-Saharan African countries. The FPC is a unique belt-like structure and a component of the flagellar pocket, which is essential for the parasite's viability. 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.
Project title: "Mechanism of Infectivity Acquisition in African Trypanosomes"
A newly approved NIH-R01 grant 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. Sum: $345,724.00 (Total: $2,311,805.00). 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.
2016-2020: The Group Dong participates in the special Doctoral Program "Integrative Structural Biology" 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.
Towards sustainable food and bioenergy security for society: Establishing an academic compound screening platform in Vienna to characterize and modulate Strigolactone synthesis in plants. Role: Research Partner (PI: Dr. T. Sieberer). Duration: 2011 - 2014.
Funded by the Austrian Federal Ministry of Education, Science and Culture. Supporting Keni Vidilaseris' PhD study during 2010-2013.