Inari Kursula: Molecular mechanisms of parasite motility
Research group information
Research group description
Malaria is one of the world's most devastating infectious diseases. Each year, nearly half a million people die of malaria. The disease is caused by Plasmodium spp., which comprise a group of unicellular, eukaryotic, intracellular parasites, belonging to the phylum Apicomplexa. They use an actomyosin motor complex, termed glideosome, for rapid gliding motility and host cell invasion. The motor components are to a large extent unique to these parasites or highly diverged from the corresponding human proteins. Parasite actin filaments are short, and their rapid treadmilling is regulated by an unusually small number of actin-binding proteins.
Our work is aimed at a mechanistic understanding of gliding motility, which malaria parasites and their relatives use for getting to and invading their host cells. We employ a broad range of biochemical, biophysical and hybrid structural biology methods for creating a complete molecular picture of the parasite actin-myosin motor and the entire glideosome. We also want to understand the evolution of apicomplexan gliding motility and eukaryotic actin-myosin motors in a broader sense. Understanding the mechanistic differences in cell motility between parasites and humans may, furthermore, open up new avenues for treatment and/or prevention of malaria.
We have determined atomic structures of malaria parasite actins in both monomeric and filamentous form and characterized their polymerization properties as well as nearly all the parasite actin-binding proteins known to date. Our future work is directed more towards larger complexes and reconstructing the entire parasite glideosome for structural and functional characterization.
My research group is divided between the Faculty of Biochemistry and Molecular Medicine at the University of Oulu, Finland, and the Department of Biomedicine, University of Bergen, Norway.
Research group members
- Inari Kursula (PhD, professor, group leader)
- Devaki Lasiwa (PhD, post-doctoral fellow)
- Stanley Makumire (PhD, post-doctoral fellow)
- Ezeogo Obaji (PhD, post-doctoral fellow)
- Henni Piirainen (PhD, post-doctoral fellow)
- Isa Pires (PhD, post-doctoral fellow)
- Maiken Fridal Trones (MSc, PhD student)
- Jude Santhampillai (MSc, PhD student)
- Ju Xu (MSc, laboratory engineer)
- Sarah Weber (MSc student)
We are always open for discussing possibilities for traineeships or MSc projects with ambitious students. In case you wish to apply for a fellowship to join our group, please contact the group leader Inari Kursula.
Full list of publications in PubMed.
Hung YF, Chen Q, Pires I, Han H, Rosenthal PB & Kursula I (2023) Structure of Toxoplasma gondii glideosome-associated connector suggests a role as an elastic element in actomyosin force generation for gliding motility. Preprint available on bioRxiv: https://doi.org/10.1101/2022.12.09.519741.
Dans MG, Piirainen H, Nguyen W, Khurana S, Mehra S, Razook Z, Geoghegan ND, Dawson AT, Das S, Schneider MP, Jonsdottir TK, Gabriela M, Gancheva MR, Tonkin C, Mollard V, Goodman CD, McFadden GI, Wilson DW, Rogers KL, Barry AE, Crabb BS, de-Koning-Ward TF, Sleebs BE, Kursula I & Gilson PR (2023) The sulfonylpiperazine MMV020291 prevents red blood cell invasion by the malaria parasite Plasmodium falciparum through interference with actin-1/profilin dynamics. PLoS Biol 21: e3002066.
Lopez AJ, Andreadaki M, Vahokoski J, Deligianni E, Calder LJ, Camerini S, Freitag A, Bergmann U, Rosenthal PB, Sidén-Kiamos I & Kursula I (2023) Structure and function of Plasmodium actin II in the parasite mosquito stages. PLoS Pathog 19: e1011174.
Pires I, Hung YF, Bergmann U, Molloy JE & Kursula I (2022) Analysis of Plasmodium falciparum myosin B ATPase activity and structure in complex with the calmodulin-like domain of its light chain MLC-B. J Biol Chem 298: 102634.
Vahokoski J, Calder L, Lopez AJ, Molloy JE, Kursula I & Rosenthal PB (2022) High-resolution structures of malaria parasite actomyosin and actin filaments. PLoS Pathog 18: e1010408.
Bendes ÁÁ, Kursula P & Kursula I (2022) Structure and function of an atypical homodimeric actin capping protein from the malaria parasite. Cell Mol Life Sci 79: 125.
Moreau CA, Quadt KA, Piirainen H, Kumar H, Bhargav SP, Strauss L, Tolja NH, Wade RC, Spatz JP, Kursula I & Frischknecht F (2020) Optical tweezers uncover a function of profilin in force generation during malaria parasite motility independent of actin binding. J Cell Sci 134: jcs233775.
Kumpula EP, Lopez AJ, Tajedin L, Han H & Kursula I (2020) Atomic view into Plasmodium actin polymerization, ATP hydrolysis, and fragmentation. PLoS Biol 17: e3000315.
Mukherjee B, Tessaro F, Vahokoski J, Kursula I, Marq JB, Scapozza L & Soldati-Favre D (2018) Modeling and resistant alleles explain the selectivity of compound 49c towards apicomplexan aspartyl proteases. EMBO J 37: e98047.
Pino P, Caldelari R, Mukherjee B, Vahokoski J, Klages N, Maco B, Collins CR, Kursula I, Blackman MJ, Heussler V, Brochet M & Soldati-Favre D (2017) A multi-stage antiplasmodial targets the plasmepsins IX and X essential for invasion and egress. Science 358: 522-528.
Green JL, Wall RJ, Vahokoski J, Yusuf NA, Ridzuan MAM, Stanway RR, Stock J, Knuepfer E, Brady D, Martin SR, Howell SA, Pires IP, Moon RW, Molloy JE, Kursula I, Tewari R & Holder AA (2017) Compositional and expression analyses of the glideosome during the Plasmodiumlife cycle reveal an additional myosin light chain required for maximum motility. J Biol Chem 292: 17857-17875.
Kumpula EP, Pires IP, Lasiwa D, Piirainen H, Bergmann U, Vahokoski J & Kursula I (2017) Apicomplexan actin polymerization depends on nucleation. Sci Rep 7: 12137.
Pospich S, Kumpula EP, von der Ecken J, Vahokoski J, Kursula I & Raunser S (2017) Near-atomic structure of jasplakinolide-stabilized malaria parasite F-actin reveals the structural basis of filament instability. Proc Natl Acad Sci 114: 10636-10641.
Moreau C, Bhargav SP, Kumar H, Quadt KA, Piirainen H, Strauss L, Kehrer J, Streichfuss M, Spatz J, Wade R, Kursula I & Frischknecht F (2017) A unique profilin-actin interface is important for malaria parasite motility. PLoS Pathog 13: e1006412.
Jacot D, Tosetti N, Pires IP, Stock J, Graindorge A, Hung YF, Han H, Tewari R, Kursula I & Soldati-Favre D (2016) An apicomplexan actin-binding protein serves as a connector and lipid sensor to coordinate motility and invasion. Cell Host Microbe 20: 731-743.
Mueller C, Samoo A, Hammoudi PM, Klages N, Kallio JP, Kursula I & Soldati-Favre D (2016) Structural and functional dissection of Toxoplasma gondii armadillo repeats only protein. J Cell Sci 129: 1031-1045.
Bhargav SP, Vahokoski J, Kallio JP, Torda A, Kursula P & Kursula I (2015) Two independently folding units of Plasmodium profilin suggest evolution via gene fusion. Cell Mol Life Sci 72: 4193-4203.
Salamun J, Kallio JP, Daher W, Soldati-Favre D & Kursula I (2014) Structure of Toxoplasma gondii coronin – an actin-binding protein that relocalizes to the posterior pole of invasive parasites and contributes to invasion and egress. FASEB J 28: 4729-4747.
Vahokoski J, Bhargav SP, Desfosses A, Andreadaki M, Kumpula EP, Muñico Martinez S, Ignatev A, Lepper S, Frischknecht F, Sidén-Kiamos I, Sachse C & Kursula I (2014) Structural differences explain diverse functions of Plasmodium actins. PLoS Pathog 10: e1004091.
Singh BK, Sattler JM, Chatterjee M, Huttu J, Schüler H & Kursula I (2011) Crystal structures explain functional differences in the two actin depolymerization factors of the malaria parasite. J Biol Chem 286: 28256-28264.
Kursula I, Kursula P, Ganter M, Panjikar S, Matuschewski K & Schüler H (2008) Structural basis for parasite‐specific functions of the divergent profilin of Plasmodium falciparum. Structure 16: 1638-1648.
- Dr. Atta Samoo (PhD student 2014-2022)
- Dr. Yu-Fu Hung (post-doctoral fellow 2016-2022)
- Jude Santhampillai (orientation student 2022)
- Léa Gelez (trainee 2022)
- Dr. Andrea Lopez Moreno (PhD student, post-doctoral fellow 2017-2021)
- Dr. Ábris Bendes (PhD student 2015-2021)
- Anne Juntunen (laboratory technician 2019-2020)
- Dr. Leila Tajedin (post-doctoral fellow 2016-2020)
- Dr. Juha Vahokoski (post-doctoral fellow 2011-2020)
- Dr. Esa-Pekka Kumpula (PhD student 2011-2019)
- Tiril Pedersen (MSc student 2018)
- Dr. Huijong Han (post-doctoral fellow 2015-2018)
- Dr. Juha Kallio (post-doctoral fellow 2011-2018)
- Manuela Mirow (trainee/BSc student 2012-2015)
- Dr. Nele Vervaet (PhD student 2010-2015)
- Dr. Moon Chatterjee (PhD student 2009-2015)
- Silvia Muñico Martinez (trainee 2012-2014)
- Markku Soronen (trainee/BSc student 2012-2014)
- Dr. Benjamin Götte (MSc student 2012-2014)
- Susanne Meier (lab technician 2009-2014)
- Dr. Saligram Prabhakar Bhargav (PhD student 2008-2014)
- Ulpu Pyy (trainee/BSc student 2012-2013)
- Dr. Gopinath Muruganandam (PhD student 2009-2013)
- Dr. Alexander Ignatev (post-doctoral fellow 2009-2013)
- Dr. Thorsten Mengesdorf (post-doctoral fellow 2010-2012)
- Dr. Avinash Kale (post-doctoral fellow 2011)
- Katharina Höfler (MSc student 2010-2011)
- Jani Huttu (MSc student 2009-2010)
- Emilia Pekkala (MSc student 2009-2010)
- Dr. Bishal Singh (MSc student 2008-2010)
- Dr. Marc Bruning (post-doctoral fellow 2009)