Dominique Soldati-Favre: Bringing Toxoplasma gondii to the Molecular World

Anyone that knows Dominique, knows that she has a real passion for science and discovery. This passion includes parasitology so it might come as a surprise that she moved to the parasitology field almost by accident. After doing a brilliant PhD in Zurich, Switzerland, in the Schümperli team, working on RNA processing, Dominique, with the support of a Swiss National Foundation postdoctoral grant and an EMBO fellowship, decided to join a lab in the US East Coast, but life decided otherwise and, in 1991, she joined John Boothroyd’s team at Stanford University, in California. This was an outstanding team, with access to exceptional facilities, but it was transitioning from working on Trypanosomes to studying Toxoplasma gondii. Although Toxoplasma was easily cultured in the lab, it had yet to be genetically modified. At a time when the genome had yet to be sequenced and molecular biology was done without kits, Dominique, with her high energy level and swiss organization, showed that Toxoplasma could be transfected, a first for an intracellular parasite (Soldati and Boothroyd, 1993). She also showed, with other team members, that the transfected parasites could be drug selected and used for transgene expression, gene knockout and complementation (Kim et al., 1993; Soldati and Boothroyd, 1995; Black et al., 1995; Soldati et al., 1995). Her work did an enormous amount for the field and things became easier afterwards. In 1995, Dominique finished her postdoctoral studies and moved to Germany to become an independent group leader. She was appointed Assistant Professor at the Center for Molecular Biology at the University of Heidelberg. There, she adapted the Cre-loxP system to Toxoplasma (Brecht et al., 1999) and revolutionized the field yet again by establishing the first inducible knockdown system for an Apicomplexa (Meissner et al., 2001; Meissner et al., 2002b). In 2001, Dominique moved her team to the Imperial College London, in the UK, where she held a position as a Senior Lecturer and Reader. In 2004, she became a Visiting Professor in parasitology at Imperial College and was appointed Associate Professor at the Faculty of Medicine of the University of Geneva, where her team is still based at, and where she became a Full Professor in 2010.

[1]  D. Soldati-Favre,et al.  Toxoplasma gondii phosphatidylserine flippase complex ATP2B-CDC50.4 critically participates in microneme exocytosis , 2021, bioRxiv.

[2]  J. Kloehn,et al.  Untargeted Metabolomics Uncovers the Essential Lysine Transporter in Toxoplasma gondii , 2021, Metabolites.

[3]  B. Maco,et al.  Revisiting the Role of Toxoplasma gondii ERK7 in the Maintenance and Stability of the Apical Complex , 2021, bioRxiv.

[4]  T. Gilberger,et al.  The ZIP Code of Vesicle Trafficking in Apicomplexa: SEC1/Munc18 and SNARE Proteins , 2020, mBio.

[5]  M. De Niz Expansion Microscopy provides new insights into the cytoskeleton of malaria parasites including the conservation of a conoid , 2020 .

[6]  P. Guichard,et al.  Expansion microscopy provides new insights into the cytoskeleton of malaria parasites including the conservation of a conoid , 2020, bioRxiv.

[7]  Rebecca D. Oppenheim,et al.  Multi-omics analysis delineates the distinct functions of sub-cellular acetyl-CoA pools in Toxoplasma gondii , 2020, BMC Biology.

[8]  Anush Chiappino-Pepe,et al.  Functional and Computational Genomics Reveal Unprecedented Flexibility in Stage-Specific Toxoplasma Metabolism. , 2020, Cell host & microbe.

[9]  J. Rayner,et al.  Genome-Scale Identification of Essential Metabolic Processes for Targeting the Plasmodium Liver Stage , 2019, Cell.

[10]  D. Soldati-Favre,et al.  Signaling Cascades Governing Entry into and Exit from Host Cells by Toxoplasma gondii. , 2019, Annual review of microbiology.

[11]  A. Sher,et al.  The lectin-specific activity of Toxoplasma gondii microneme proteins 1 and 4 binds Toll-like receptor 2 and 4 N-glycans to regulate innate immune priming , 2019, PLoS pathogens.

[12]  D. Soldati-Favre,et al.  The triumvirate of signaling molecules controlling Toxoplasma microneme exocytosis: Cyclic GMP, calcium, and phosphatidic acid , 2019, PLoS pathogens.

[13]  Christopher J. Tonkin,et al.  An apically located hybrid guanylate cyclase–ATPase is critical for the initiation of Ca2+ signaling and motility in Toxoplasma gondii , 2019, The Journal of Biological Chemistry.

[14]  D. Soldati-Favre,et al.  Phosphatidic acid governs natural egress in Toxoplasma gondii via a guanylate cyclase receptor platform , 2019, Nature Microbiology.

[15]  K. Brown,et al.  Essential cGMP Signaling in Toxoplasma Is Initiated by a Hybrid P-Type ATPase-Guanylate Cyclase. , 2018, Cell host & microbe.

[16]  S. Rouse,et al.  Structural Basis of Phosphatidic Acid Sensing by APH in Apicomplexan Parasites , 2018, Structure.

[17]  B. Maco,et al.  Toxoplasma gondii TFP1 is an essential transporter family protein critical for microneme maturation and exocytosis , 2018, Molecular microbiology.

[18]  J. Choudhary,et al.  Crosstalk between PKA and PKG controls pH‐dependent host cell egress of Toxoplasma gondii , 2017, The EMBO journal.

[19]  M. Blackman,et al.  A multistage antimalarial targets the plasmepsins IX and X essential for invasion and egress , 2017, Science.

[20]  Vassily Hatzimanikatis,et al.  Bioenergetics-based modeling of Plasmodium falciparum metabolism reveals its essential genes, nutritional requirements, and thermodynamic bottlenecks , 2017, PLoS Comput. Biol..

[21]  R. Tewari,et al.  An Apicomplexan Actin-Binding Protein Serves as a Connector and Lipid Sensor to Coordinate Motility and Invasion. , 2016, Cell host & microbe.

[22]  D. Soldati-Favre,et al.  Phosphatidic Acid-Mediated Signaling Regulates Microneme Secretion in Toxoplasma. , 2016, Cell host & microbe.

[23]  D. Soldati-Favre,et al.  The Conoid Associated Motor MyoH Is Indispensable for Toxoplasma gondii Entry and Exit from Host Cells , 2016, PLoS pathogens.

[24]  Christopher J. Tonkin,et al.  Two Essential Light Chains Regulate the MyoA Lever Arm To Promote Toxoplasma Gliding Motility , 2015, mBio.

[25]  Jens Nielsen,et al.  Metabolic Needs and Capabilities of Toxoplasma gondii through Combined Computational and Experimental Analysis , 2015, PLoS Comput. Biol..

[26]  W. Daher,et al.  Structure of Toxoplasma gondii coronin, an actin‐binding protein that relocalizes to the posterior pole of invasive parasites and contributes to invasion and egress , 2014, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[27]  Malcolm J. McConville,et al.  BCKDH: The Missing Link in Apicomplexan Mitochondrial Metabolism Is Required for Full Virulence of Toxoplasma gondii and Plasmodium berghei , 2014, PLoS pathogens.

[28]  Rebecca D. Oppenheim,et al.  The 2-methylcitrate cycle is implicated in the detoxification of propionate in Toxoplasma gondii , 2013, Molecular microbiology.

[29]  M. Llinás,et al.  A Tetracycline-Repressible Transactivator System to Study Essential Genes in Malaria Parasites , 2012, Cell host & microbe.

[30]  D. Soldati-Favre,et al.  Galactose Recognition by the Apicomplexan Parasite Toxoplasma gondii* , 2012, The Journal of Biological Chemistry.

[31]  G. Marth,et al.  A DOC2 Protein Identified by Mutational Profiling Is Essential for Apicomplexan Parasite Exocytosis , 2012, Science.

[32]  L. Sibley,et al.  Solution structure and dynamics of ADF from Toxoplasma gondii. , 2011, Journal of structural biology.

[33]  Eugene A. Kapp,et al.  Quantitative in vivo Analyses Reveal Calcium-dependent Phosphorylation Sites and Identifies a Novel Component of the Toxoplasma Invasion Motor Complex , 2011, PLoS pathogens.

[34]  Dominique Soldati-Favre,et al.  Functional dissection of the apicomplexan glideosome molecular architecture. , 2010, Cell host & microbe.

[35]  W. Daher,et al.  Concerted Action of Two Formins in Gliding Motility and Host Cell Invasion by Toxoplasma gondii , 2010, PLoS pathogens.

[36]  Dominique Soldati-Favre,et al.  Toxoplasma gondii transmembrane microneme proteins and their modular design , 2010, Molecular microbiology.

[37]  Dominique Soldati-Favre,et al.  Versatility in the acquisition of energy and carbon sources by the Apicomplexa , 2010, Biology of the cell.

[38]  L. Sibley,et al.  Toxoplasma gondii Actin Depolymerizing Factor Acts Primarily to Sequester G-actin* , 2009, The Journal of Biological Chemistry.

[39]  M. Blackman,et al.  Members of a Novel Protein Family Containing Microneme Adhesive Repeat Domains Act as Sialic Acid-binding Lectins during Host Cell Invasion by Apicomplexan Parasites* , 2009, The Journal of Biological Chemistry.

[40]  F. Frischknecht,et al.  Microneme protein 8 – a new essential invasion factor in Toxoplasma gondii , 2008, Journal of Cell Science.

[41]  Marie-France Carlier,et al.  Toxoplasma profilin is essential for host cell invasion and TLR11-dependent induction of an interleukin-12 response. , 2008, Cell host & microbe.

[42]  P. Simpson,et al.  Atomic resolution insight into host cell recognition by Toxoplasma gondii , 2007, The EMBO journal.

[43]  D. Soldati,et al.  Conditional expression of Toxoplasma gondii apical membrane antigen-1 (TgAMA1) demonstrates that TgAMA1 plays a critical role in host cell invasion. , 2005, Molecular biology of the cell.

[44]  T. Mann,et al.  Identification of the membrane receptor of a class XIV myosin in Toxoplasma gondii , 2004, The Journal of cell biology.

[45]  L. Sibley,et al.  Rapid invasion of host cells by Toxoplasma requires secretion of the MIC2–M2AP adhesive protein complex , 2003, The EMBO journal.

[46]  D. Soldati,et al.  Role of Toxoplasma gondii Myosin A in Powering Parasite Gliding and Host Cell Invasion , 2002, Science.

[47]  D. Soldati,et al.  ‘The glideosome’: a dynamic complex powering gliding motion and host cell invasion by Toxoplasma gondii , 2002, Molecular microbiology.

[48]  D. Soldati,et al.  Toxoplasma gondii myosin A and its light chain: a fast, single‐headed, plus‐end‐directed motor , 2002, The EMBO journal.

[49]  J. Ajioka,et al.  A family of transmembrane microneme proteins of Toxoplasma gondii contain EGF-like domains and function as escorters. , 2002, Journal of cell science.

[50]  H. Bujard,et al.  Modulation of myosin A expression by a newly established tetracycline repressor-based inducible system in Toxoplasma gondii. , 2001, Nucleic acids research.

[51]  L. Sibley,et al.  The Toxoplasma Micronemal Protein MIC4 Is an Adhesin Composed of Six Conserved Apple Domains* , 2001, The Journal of Biological Chemistry.

[52]  D. Soldati,et al.  Identification and Characterization of an Escorter for Two Secretory Adhesins in Toxoplasma gondii , 2001, The Journal of cell biology.

[53]  D. Ferguson,et al.  The microneme protein MIC4, or an MIC4-like protein, is expressed within the macrogamete and associated with oocyst wall formation in Toxoplasma gondii. , 2000, International journal for parasitology.

[54]  D. Soldati,et al.  Two Conserved Amino Acid Motifs Mediate Protein Targeting to the Micronemes of the Apicomplexan ParasiteToxoplasma gondii , 2000, Molecular and Cellular Biology.

[55]  D. Soldati,et al.  Genome engineering of Toxoplasma gondii using the site-specific recombinase Cre. , 1999, Gene.

[56]  L. Sibley,et al.  Participation of myosin in gliding motility and host cell invasion by Toxoplasma gondii , 1997, Molecular microbiology.

[57]  L. Sibley,et al.  Toxoplasma Invasion of Mammalian Cells Is Powered by the Actin Cytoskeleton of the Parasite , 1996, Cell.

[58]  J. Boothroyd,et al.  Complementation of a Toxoplasma gondii ROP1 knock-out mutant using phleomycin selection. , 1995, Molecular and biochemical parasitology.

[59]  J. Boothroyd,et al.  Restriction enzyme-mediated integration elevates transformation frequency and enables co-transfection of Toxoplasma gondii. , 1995, Molecular and biochemical parasitology.

[60]  J. Boothroyd,et al.  A selector of transcription initiation in the protozoan parasite Toxoplasma gondii , 1995, Molecular and cellular biology.

[61]  J. Boothroyd,et al.  Gene replacement in Toxoplasma gondii with chloramphenicol acetyltransferase as selectable marker. , 1993, Science.

[62]  J. Boothroyd,et al.  Transient transfection and expression in the obligate intracellular parasite Toxoplasma gondii , 1993, Science.

[63]  Slobodan Dmitrović Conditional Expression , 2021, Modern C for Absolute Beginners.

[64]  M VALENTINCIC,et al.  [Toxoplasma gondii]. , 1953, Zdravstveni vestnik.