Project

Back to overview

Pathogen-host cell interactions during the liver stage of Plasmodium parasites

English title Pathogen-host cell interactions during the liver stage of Plasmodium parasites
Applicant Heussler Volker
Number 140691
Funding scheme Project funding
Research institution Institut für Zellbiologie Departement Biologie Universität Bern
Institution of higher education University of Berne - BE
Main discipline Experimental Microbiology
Start/End 01.08.2012 - 31.07.2015
Approved amount 402'000.00
Show all

All Disciplines (6)

Discipline
Experimental Microbiology
Zoology
Cellular Biology, Cytology
Medical Microbiology
Tropical Medicine
Immunology, Immunopathology

Keywords (7)

signalling; parasite egress; intravital imaging; autophagy; host-pathogen interaction; Liver stage; Malaria

Lay Summary (English)

Lead
Lay summary

Plasmodium development in hepatocytes and parasite egress from hepatocytes are both highly coordinated events. Although some key steps of the development of the exo-erythrocytic parasite have recently been deciphered, many questions remain to be answered. We propose to investigate parasite-host cell interactions during the late liver stage with the emphasis on i) parasite strategies to exploit host cell resources, ii) molecular analysis of parasite egress and iii) innate immune responses provoked by this event. In particular, the role of parasite-induced host cell autophagy as a possible source of nutrients will be investigated. Autophagy-modifying drugs as well as autophagy mouse models will be used. Parasite egress from the intracellular vacuole is normally followed by host cell death and we intend to identify the responsible parasite proteins. Parasite proteases are most likely involved in these events and it is planned to identify and target them by knockout strategies and specific inhibitors. Phagocytes are recruited to the site of infection and we will investigate the time course of this infiltration and its relationship to the release of packed merozoites into blood vessels. The information gained from these approaches will be of use in generating improved attenuated parasites for vaccination trials in mice.


Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
High resolution microscopy reveals an unusual architecture of the Plasmodium berghei endoplasmic reticulum.
Kaiser Gesine, De Niz Mariana, Zuber Benoît, Burda Paul-Christian, Kornmann Benoît, Heussler Volker T, Stanway Rebecca R (2016), High resolution microscopy reveals an unusual architecture of the Plasmodium berghei endoplasmic reticulum., in Molecular microbiology, 102(5), 775-791.
Plasmodium
Heussler Volker, Spielmann Tobias, Frischknecht Friedrich, Gilberger Tim (2016), Plasmodium, in Walochnik Julia (ed.), Springer, Wien, 241.
Progress in imaging methods: insights gained into Plasmodium biology.
De Niz Mariana, Burda Paul-Christian, Kaiser Gesine, Del Portillo Hernando A, Spielmann Tobias, Frischknecht Freddy, Heussler Volker T (2016), Progress in imaging methods: insights gained into Plasmodium biology., in Nature reviews. Microbiology, ePub.
Protective efficacy and safety of liver stage attenuated malaria parasites.
Kumar Hirdesh, Sattler Julia Magdalena, Singer Mirko, Heiss Kirsten, Reinig Miriam, Hammerschmidt-Kamper Christiane, Heussler Volker, Mueller Ann-Kristin, Frischknecht Friedrich (2016), Protective efficacy and safety of liver stage attenuated malaria parasites., in Scientific reports, 6, 26824-26824.
A Plasmodium Phospholipase Is Involved in Disruption of the Liver Stage Parasitophorous Vacuole Membrane
Burda Paul-Christian, Roelli Matthias A., Schaffner Marco, Khan Shahid M., Janse Chris J., Heussler Volker T. (2015), A Plasmodium Phospholipase Is Involved in Disruption of the Liver Stage Parasitophorous Vacuole Membrane, in PLOS PATHOGENS, 11(3), 1-25.
In Vivo and In Vitro Characterization of a Plasmodium Liver Stage-Specific Promoter
De Niz Mariana, Helm Susanne, Horstmann Sebastian, Annoura Takeshi, del Portillo Hernando A., Khan Shahid M., Heussler Volker T. (2015), In Vivo and In Vitro Characterization of a Plasmodium Liver Stage-Specific Promoter, in PLOS ONE, 10(4), 1-17.
Long-term live imaging reveals cytosolic immune responses of host hepatocytes against Plasmodium infection and parasite escape mechanisms
Prado Monica, Heussler Volker, Schmuckli-Maurer Jacqueline, Niklaus Livia, Caldelari Reto, Wacker Rahel, De Niz Mariana, Eickel Nina, Agop-Nersesian Carolina, Meyer Christian, Janse Chris, Khan Shahid, May Jürgen, Heitmann Anna (2015), Long-term live imaging reveals cytosolic immune responses of host hepatocytes against Plasmodium infection and parasite escape mechanisms, in Autophagy, 11(9), 1561-1579.
A Cysteine Protease Inhibitor of Plasmodium berghei Is Essential for Exo-erythrocytic Development
Lehmann Christine, Heitmann Anna, Mishra Satish, Burda Paul-Christian, Singer Mirko, Prado Monica, Niklaus Livia, Lacroix Celine, Menard Robert, Frischknecht Friedrich, Stanway Rebecca, Sinnis Photini, Heussler Volker (2014), A Cysteine Protease Inhibitor of Plasmodium berghei Is Essential for Exo-erythrocytic Development, in PLOS PATHOGENS, 10(8), e1004336.
Imaging of the spleen in malaria
Heussler Volker (2014), Imaging of the spleen in malaria, in Parasitol Int. , 195.

Collaboration

Group / person Country
Types of collaboration
Prof. Henando del Portillo, University of Barcelona Spain (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. David Fidock, Columbia University United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Christian Meyer, Bernhard-Nocht-Institute, Hamburg Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
PD Dr. Thomas Jacobs Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. Photini Sinnis, New York University United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. Chris Janse Netherlands (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Dr. Asif Mohmmed India (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
- Industry/business/other use-inspired collaboration
Prof. Matthias Marti Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Dr. Tobias Spielmann Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. Christian Doerig, Monash University, Melbourne Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Symposium: Malaria and friends Talk given at a conference Plasmodium liver stage 14.11.2016 Marburg, Germany Heussler Volker;
DGHM, annual Meeting Talk given at a conference Cytosolic immune responses in Plasmodium-infected hepatocytes and parasite escape mechanism 11.09.2016 Ulm, Germany Heussler Volker;
DGP Annual Meeting Talk given at a conference Plasmodium liver stage 09.03.2016 Göttingen, Germany Heussler Volker;
ICGEB seminar Individual talk Conserved machinery underlying malaria virulence in rodents and humans 25.02.2015 New Delhi, India Kaiser Gesine; Stanway Rebecca; Burda Paul-Christian; De Niz Hidalgo Mariana; Heussler Volker;
Evimalar Cluster meeting Talk given at a conference Cytosolic immune responses of host hepatocytes against Plasmodium infection and parasite escape mechanisms 03.10.2014 Genf, Switzerland De Niz Hidalgo Mariana; Heussler Volker;
Swiss Apoptosis Meeting Talk given at a conference Cytosolic immune responses of host hepatocytes against Plasmodium infection and parasite escape 10.09.2014 Bern, Switzerland Eickel Nina; De Niz Hidalgo Mariana; Heussler Volker; Agop-Nersesian Carolina; Niklaus Livia; Wacker Rahel;
PARATROP 2014 Talk given at a conference Intravital imaging offers new insights in host-parasite interaction 16.07.2014 Zürich, Switzerland Agop-Nersesian Carolina; Niklaus Livia; De Niz Hidalgo Mariana; Wacker Rahel; Burda Paul-Christian; Stanway Rebecca; Eickel Nina; Heussler Volker; Kaiser Gesine;
Biology of parasitism course Individual talk Plasmodium liver stage biology 14.07.2014 Woods Hole, MA, United States of America Heussler Volker; Agop-Nersesian Carolina; Burda Paul-Christian; Kaiser Gesine; Eickel Nina; Stanway Rebecca; Wacker Rahel; Niklaus Livia; De Niz Hidalgo Mariana;
Frontiers in Parasitology Talk given at a conference Cytosolic immune responses of host hepatocytes against Plasmodium infection and parasite escape 29.06.2014 Berlin, Germany Eickel Nina; Wacker Rahel; De Niz Hidalgo Mariana; Niklaus Livia; Agop-Nersesian Carolina; Heussler Volker;
Gordon Research Conference Talk given at a conference Two sides of the same coin: beneficial and deleterious effects of host cell autophagy in Plasmodium infected hepatocytes 08.06.2014 New Port, United States of America Niklaus Livia; Wacker Rahel; Eickel Nina; Heussler Volker; Agop-Nersesian Carolina; De Niz Hidalgo Mariana;
Seminar Tropeninstitut Basel Individual talk Plasmodium berghei infection provokes cytosolic immune responses of host hepatocytes 28.05.2014 Basel, Switzerland Agop-Nersesian Carolina; Wacker Rahel; De Niz Hidalgo Mariana; Eickel Nina; Niklaus Livia; Kaiser Gesine; Heussler Volker;
Foundation Schlumberger Talk given at a conference Cytosolic immune responses of host hepatocytes against Plasmodium infection and parasite escape mechanisms 15.04.2014 Nizza, France Agop-Nersesian Carolina; Eickel Nina; Heussler Volker; De Niz Hidalgo Mariana; Niklaus Livia;
Indo-Swiss meeting New Delhi Talk given at a conference Liver stage development and organelle segregation in Plasmodium liver stage parasites 02.12.2013 New Delhi, India Heussler Volker; Eickel Nina;
SPP 1580 International Conference on Intracellular Niches of Pathogens Talk given at a conference Plasmodium berghei infection of hepatocytes provokes a non-canonical LC3 association with the parasitophorous vacuole membrane 26.09.2013 Glashütten, Germany Eickel Nina; Wacker Rahel; Heussler Volker; De Niz Hidalgo Mariana; Niklaus Livia; Agop-Nersesian Carolina;
Biology of Parasitism course; Woods Hole; MA Individual talk Plasmodium liver stage biology 28.06.2013 Woods Hole, MA, United States of America Wacker Rahel; Heussler Volker; Eickel Nina; Stanway Rebecca; Burda Paul-Christian; De Niz Hidalgo Mariana; Kaiser Gesine;
World Malaria Day Symposium Talk given at a conference Plasmodium liver stage parasites induce distinct autophagy-related events in host hepatocytes 24.04.2013 Baltimore, United States of America Stanway Rebecca; Heussler Volker; Agop-Nersesian Carolina; Kaiser Gesine; Niklaus Livia; De Niz Hidalgo Mariana; Wacker Rahel; Eickel Nina; Burda Paul-Christian;
University seminar Individual talk Plasmodium liver stage parasites induce distinct autophagy-related events in host hepatocytes 10.04.2013 Barcelona, Spain Heussler Volker; Stanway Rebecca; Eickel Nina;
International Seminar Individual talk Regulated proteolytic activity is required for motility and invasion of Plasmodium sporozoites 14.03.2013 Glasgow, Great Britain and Northern Ireland Heussler Volker;
Paul-Ehrlich-Institute Seminar Individual talk Host cell autophagy supports growth of Plasmodium liver stage parasites 21.02.2013 Frankfurt, Germany Eickel Nina; Heussler Volker;
Malaria Talk given at a conference Host cell autophagy supports growth of Plasmodium liver stage parasites 20.01.2013 New Orleans, United States of America Burda Paul-Christian; Agop-Nersesian Carolina; De Niz Hidalgo Mariana; Eickel Nina; Wacker Rahel; Kaiser Gesine; Heussler Volker; Stanway Rebecca; Niklaus Livia;
MIC symposium Talk given at a conference Malaria research: Intravital imaging offers new insights in host-parasite interaction 07.12.2012 Bern, Switzerland Burda Paul-Christian; Eickel Nina; Heussler Volker;
Annual meeting DGHM Talk given at a conference Plasmodium liver stage parasites induce host cell autophagy 30.09.2012 Hamburg, Germany Eickel Nina; Stanway Rebecca; Heussler Volker;


Self-organised

Title Date Place
Retreat on Plasmodium virulence factors and protein export 08.03.2015 Rotenfels bei Basel, Switzerland
Evimalar Cluster meeting 03.10.2014 Genf, Switzerland

Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Gemeinsam gegen Malaria SystemsX newsletter Italian-speaking Switzerland Rhaeto-Romanic Switzerland German-speaking Switzerland Western Switzerland 2014

Awards

Title Year
Best talk, BioMalPar annual Meeting 2015
Preis für besten Vortrag, BioMalPar Meeting 2015 2015
Posterpreis, Parasitology meeting Woods Hole, MA 2014
Posterpreis, Parasitology meeting Woods Hole 2013 2013
Preis für besten Vortrag, SSTMP PhD retreat Engelberg 2013

Associated projects

Number Title Start Funding scheme
157704 Direct electron detector and phase plate for cryo-transmission electron microscopy of biological samples 01.12.2014 R'EQUIP
150823 Serial block face SEM 01.12.2013 R'EQUIP
159519 Pathogen-host cell interactions during the liver stage of Plasmodium parasites 01.08.2015 Project funding
145013 Multimode Live Imaging - University of Bern (MLI-be) 01.04.2013 R'EQUIP
150824 White-Laser Confocal Microscopy: Modular and Sensitive Multi-channel Analysis 01.12.2013 R'EQUIP

Abstract

Plasmodium development in hepatocytes and parasite egress from hepatocytes are both highly coordinated events. Although some key steps of the development of the exo-erythrocytic parasite have recently been deciphered, many questions remain to be answered. We propose to investigate parasite-host cell interactions during the late liver stage with the emphasis on i) parasite strategies to exploit host cell resources, ii) molecular analysis of parasite egress and iii) innate immune responses provoked by this event. In particular, the role of parasite-induced host cell autophagy as a possible source of nutrients will be investigated. Autophagy-modifying drugs as well as autophagy mouse models will be used. Parasite egress from the intracellular vacuole is normally followed by host cell death and we intend to identify the responsible parasite proteins. The putative proteases DPAP3 and SERA3 are most likely involved in these events and will be targeted by conditional knockout strategies and specific inhibitors. Phagocytes are recruited to the site of infection and we will investigate the time course of this infiltration and its relationship to the release of packed merozoites into blood vessels. The information gained from these approaches will be of use in generating improved attenuated parasites for vaccination trials in mice.
-