IRP APICOLIPID

IRP APICOLIPID

French-Australian International Research Project in Biology

IRP APICOLIPID
2018-2022
Project Coordinator:
Dr Cyrille Botté 
cyrille.botte(at)univ-grenoble-alpes.fr
Twitter: @ApicoLipid 

Coordinator partner: 
Prof Geoff McFadden

IRP APICOLIPID
Website

Apicoplast in malaria

magnetic beads

Zoom basal caps and rigs Full Resolution midlate division 3

Graphical abstract

Toxoplasma ATS2

Introduction

The CNRS-INSERM IRP ApicoLipid (Apicomplexan parasites lipid and membrane biogenesis) is managed by Dr Cyrille Botté (IAB CNRS UMR5309 INSERM U1209, Université Grenoble Alpes) in collaboration with Professor Geoff McFadden (School of Biosciences, University of Melbourne). Our IRP was initiated through a long term and fruitful collaboration between our two laboratories initially supported by a CNRS International Scientific Project (PICS 2013-2017) and through our IRP in 2018. Our consortium aims to better understand the role propagation and pathogenicity of infectious agents causing malaria and toxoplasmosis to identify novel drug targets.

Missions and research themes

Apicomplexan parasites are unicellular eukaryotes responsible for major human infectious and chronic diseases such as malaria and toxoplasmosis, which cause massive social and economic burden. Malaria is caused by Plasmodium spp., via the bite of Anopheles mosquitoes in tropical and sub-tropical areas. Plasmodium infects ±200 million people every year and is responsible for the death of ±450,000, mainly children under the age of 8. Toxoplasma gondii is the causative agent of toxoplasmosis, a global chronic disease that affects ±1/3 of the world population. T. gondii is a lethal threat for the foetus of primo-infected pregnant women and for any immunocompromised patients (HIV, leukemia, chemotherapies, organ transplant…). To date, there is no efficient vaccine against these parasites, and parasite are rapidly developing resistance to most marketed molecules, especially for malaria. Thus, there is a pressing need for the identification of new targets and efficient drugs.

Apicomplexa are obligate intracellular parasites of humans, which means that they have to invade a host cell to survive and propagate. Current evidences strongly support lipid synthesis and membrane biogenesis as crucial pathways for parasite propagation in humans and therefore represent pertinent drug targets.

Our consortium focuses on understanding how this group of infectious parasites can acquire the lipid required for their survival. Our IRP combines a strong expertise, long lasting collaboration and complementary expertise to decipher the complex metabolic pathways sustaining parasite survival in the human hhost. We use a combination of novel genetic edition of the parasite (CrispR-Cas9-based), mass spectrometry-based lipidomics and fluxomics approaches developed in the metabolomic platform developed on the French side (Dr Botté, GEMELI Université Grenoble Alpes) as well as full life cycle analysis of the parasite lipid synthesis via the unique insectarium and mice facility of the Australian partner (Prof McFadden University of Melbourne). Through our interaction, we showed that the parasite can actively scavenge the human host lipid resources, but can also synthesize lipids de novo via a relict non-photosynthetic plastid (i.e. the apicoplast). Importantly, we showed that the parasite has to combine lipids from both host and de novo sources to survive. Recently we also showed that the parasite is also capable to metabolically reprogram both pathways upon the physiological and nutritional environment of their host. We currently focus on understanding how the parasite can sense and adapt to the host and how this is happening in the malaria mosquito vector. Together with our partners (Prof McConville Bio21 University of Melbourne, Dr Christopher Tonkin WEHI Melbourne), we form a taskforce to decipher parasite lipid biology, find the parasite weaknesses that could potentially benefit malaria and toxoplasmosis patients worldwide.

MAIN PROJECT OF RESEARCH THEMES

  • Understand the pathways of lipid channeling, recycling and combination between the host and the parasite
  • Determine the specificity of lipid synthesis throughout the whole parasite life cycle
  • Contribute to the global knowledge of the intracellular development, lipid synthesis, membrane biogenesis, nutrient acquisition of apicomplexa parasite within their host
  • Identify novel drug targets against malaria and toxoplasmosis
  • Teach and promote novel techniques developed by the consortium: metabolomics/lipidomics/fluxomics; malaria liver and mosquito analysis, molecular approaches in malaria and toxoplasmosis
  • Promote the environment young researcher (PhD, Postdoc, technicians…) to develop their skills and career
  • Promote French and Australian research and knowledge

institutions and laboratories involved

France

Australia

  • Prof McFadden, School of Biosciences, University of Melbourne
  • Prof Malcolm McConville, Bio21 Institute, University of Melbourne
  • Dr Christopher Tonkin, Walter Eliza Health Institute (WEHI) Melbourne

some key publications

Amiar+ S, Katris+ NJ, Berry L, Dass S, Shears MJ, Brunet C, Touquet B, Hakimi MA, McFadden GI, Yamaryo-Botté Y*, Botté CY*. Division and adaptation to host nutritional environment of apicomplexan parasites depend on apicoplast lipid metabolic plasticity and host organelles remodelling, (2020) Cell Rep. 2020 Mar 17;30(11):3778-3792.e9. doi: 10.1016/j.celrep.2020.02.072.

Yang L, Uboldi AD, Seizova S, Wilde ML, Coffey MJ, Katris NJ, Yamaryo-Botté Y, Kocan M, Bathgate RAD, Stewart RJ, McConville MJ, Thompson PE, Botté CY, Tonkin CJ. J Biol Chem. An apically located hybrid guanylate cyclase-ATPase is critical for the initiation of Ca2+ signaling and motility in Toxoplasma gondii. J Biol Chem 2019 May 31;294(22):8959-8972. doi: 10.1074/jbc.RA118.005491

Uboldi AD, Wilde ML, McRae EA, Stewart RJ, Dagley LF, Yang L, Katris NJ, Hapuarachchi SV, Coffey MJ, Lehane AM, Botte CY, Waller RF, Webb AI, McConville MJ, Tonkin CJ. Protein kinase A negatively regulates Ca2+ signalling in Toxoplasma gondii. PLoS Biol. 2018 Sep 12;16(9):e2005642. doi: 10.1371/journal.pbio.2005642.

Shears MJ, MacRae JI, Goodman DG, Mollard VSU, Botté CY *, McFadden GI*. (2017). Characterization of the Plasmodium falciparum and P. berghei glycerol-3-phosphate acyltranferase involved in FASII fatty acid utilization in the malaria parasite apicoplast. Cellular Microbiology 19(1). PMCID:PMC5213128.

Amiar S, MacRae JI, Callahan DL, vanDooren GG, Shears MJ, Dubois D, Cesbron-Delauw MF, Maréchal E, McConville MJ, McFadden GI, Yamaryo-Botté Y*, BOTTÉ CY *.  The Toxoplasma gondii apicoplast is responsible for bulk phospholipid synthesis mainly via a plant-like glycerol 3-phosphate acyltransferase for lysophosphatidic acid precursor assembly. Plos Pathogens 2016 Aug 4;12(8):e1005765. doi: 10.1371/journal.ppat.1005765

BOTTÉ CY*, Yamaryo-Botté Y, Rupasinghe TW, Mullin KA, MacRae JI, Spurck TP, Kalanon M, Shears MJ, Coppel RL, Crellin PK, Maréchal E, McConville MJ, McFadden GI*. Atypical lipid composition in the purified relict plastid (apicoplast) of malaria parasites. (*co-corresponding) Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7506-11.

Signature of the LIA APICOLIPID CNRS INSERM at the Australian Science Academy, with CNRS CEO Antoine Petit

Press release medical News 2016

Press release INSB april 2020

Metabolomic day I IAB February 2020

Metabolomic day I IAB February 2020

Journal of lipid Research takeover

IEA GOAL

IEA GOAL

French-Australian International Emerging Action on Biology

IEA GOAL
2018-2020
Contact:
Dr. Etienne Coutureau
etienne.coutureau(at)u-bordeaux.fr

Pr. Bernard Balleine
email

IEA GOAL
News

Caption

Introduction

The IEA GOAL (International Emerging Action “The Neural Basis of goal-directed behaviour in rats“), managed by Dr. Etienne Coutureau (Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS –Bordeaux University) in collaboration with Pr. Bernard Balleine (University of New South Wales, Sydney, Australia) has started in 2018 and will run until the end of 2020.

Missions and research themes

Decision making is an essential component of our life in a world of increasing social complexity, means for communication, and technological advances. Solving problems and adapting to new situations requires the integration of the pursued goal with the possible values and consequences of our decisions. In ecological situations, animals and humans are able to flexibly adapt their performance according to changes in the environment. Understanding how the brain integrates goal information is a fundamental issue and has major implications at both theoretical and applied levels. The GOAL project  integrates into this rapidly expanding international initiative to understand the neurocognitive bases of goal-directed decision making.

Main OBJECTIVES OF THE PROJECT

Research in this field calls upon complementary competences, cross-disciplinary exchanges and effective cooperation. This is achieved in the present project by bringing together major actors in France (E. Coutureau, Bordeaux) and Australia (B. Balleine, S. Killcross, Sydney) who together have the ambition of fostering a world-class network for research theory and methods on goal implementation

In the present proposal, we aim at sharing data and ideas through people exchanges and minisymposia organisation,  in both  Bordeaux and  Sydney in order to elucidate the brain dynamics of information exchanges.

institutions and laboratories involved

France

  • Dr. Etienne Coutureau (Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS –Bordeaux University)

Australia

  • Pr. Bernard Balleine (School of Psychology, University of New South Wales, Sydney)

 

Read more

Caption

IRL BMC²

IRL BMC²

International Research Laboratory between France and Singapore in Mechanobiology, Imaging and Biophysics

IRL BMC²

Creation date: 2014
Contact:
Pr. Virgile Viasnoff
Virgile.viasnoff(at)escpi.fr

IRL BMC²
Website

Introduction

The International Research Laboratory BMC² Biomechanics of Cell-Cell Contacts is part of the Mechanobiology institute of Singapore. It is one of the 75 IRL developed by the CNRS with strategic partners across the world and one of the 5 IRL in Singapore. It is directed by Virgile Viasnoff who funded it in 2014. It is composed of about 15 peoples including Postdocs. PhD students and Research assistant. It benefits and contributes to the unique setting of the institute to bring together very interdisciplinary researchers ( biology, physics, optic computing, material science) to study mechanobiology ie the role of mechanics in Biology.

In ten years we built numerous collaboration locally and world wide with the support of France (ANR) and Singapore alike (NRF).

Mission and research themes

Mission: To push mechanobiology of cell junction to another  understanding level with the development of new imaging techniques, new biophysical understanding and commercial product development. We aim at fostering the best of both countries in the filed.

Research  directions:  Epithelial cell cell contact, Liver development, new imaging HCS platform, artificial microniches, Technologies for Organoids

MAIN projects of research

Technology driven:

1- Membwell: a new approach to control microenvironement from the cellular to the organoid level. Achievements: a platform that can create up to 600 diffefrent types of environments,

2- SoSPIM: A new approach to perform light sheet microscopy by embedding micromirrors in the cell culture dish.

Achievement: a High content screening platform for Orgnaoids with 3D imaging of 100 orgnaoids in 10 minutes.

Biophysics:

  • Biophysics of cell-cell contact: we aim at understanding the role of the physical properties of cell cell junction in its adhesion strength using all sorts of techniques.

Constructing a liver one cell at a time. Inducing liver function with a minimal number of cells, control bile production in artificial livers.

laboratories involved

France
CNRS

Singapore

National University of Singapore: MBI

IRP SoCNetMM

IRP SoCNetMM

French-Australian IRP in biology

IRP SoCNetMM
2020 – 2024
Contact:
Isabelle Charrier (NeuroPSI, CNRS), isabelle.charrier(at)u-psud.fr

Rob Harcourt (MPRG, Macquarie University)
robert.harcourt(at)mq.edu.au

IRP SoCNetMM
News

Australian sea lion pup approaching the speaker during a playback test using the calls of its mother (credit: I. Charrier)

Visual discrimination experiment on Australian sea lion mother (credit: I. Charrier)

Setting the camp for a one-month fieldwork trip on Olive Island (South Australia) (credit: I. Charrier)

Introduction

The IRP SoCNetMM (Social Communication Network in Marine Mammals), managed by Isabelle Charrier (UMR9197 CNRS Paris Saclay Institute of Neuroscience) in collaboration wit Pr. Robert Harcourt (Macquarie University) started in 2020 but is the follow-up of the LIA MCoMM (Multimodal Communication in Marine Mammals, 2015-2018).

Missions and research themes

Sensory information used in animal communication is complex and understanding how it is produced, emitted, transmitted, and then perceived and integrated is a challenge for biologists. The task becomes even more complex when considering multiple sensory modalities. Among animals living in social groups, individuals form communication networks that are essential to mediate social interactions. Signalling individual identity and other phenotypic traits can facilitate social interactions, mate selection and intra-sexual competition. The perception of such information can have strong impact on the breeding success of individuals, as well as on their survival rate. We propose to explore the social communication network in Australian sea lions (ASL) in a highly innovative project which will provide essential information on how vocal, olfactory and visual signals are used in social recognition at different levels of relationships: mother-pup recognition, male-male assessment, kin-recognition for inbreeding avoidance, and recognition between adult social partners. The functions of several sensory channels will be assessed by experimental manipulations to understand which sensory cues are essential, and in which context, to establish individual recognition and how they regulate individual behaviour and social networks.

MAIN PROJECTS OF RESEARCH

– Investigation on sensory modalities and their interactions: olfactory recognition and olfactory abilities in air and under water; individual visual recognition, cross-modal recognition.

– Social Network and communication: vocal and olfactory cues to avoid inbreeding; male breeding strategy and vocal assessment; social interaction and vocal recognition in pups.

– PhD funding(s)

– Involvement of French and Australian master students

institutions and laboratories involved

France

  • Isabelle Charrier, NeuroPSI (Paris Saclay Institute of Neuroscience) UMR CNRS 9197 – Université Paris Saclay
  • Benoist Schaal, CSGA (Centre des Sciences du Goût et de l’Alimentation) UMR CNRS 6265 – Université de Bourgogne
  • Gérard Coureaud, CRNL (Centre de Recherche en Neurosciences de Lyon), UMR CNRS 5292 – Université de Lyon
  • Nicolas Barthes, Aurélie Célérier, Sylvia Campagna, CEFE (Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), UMR CNRS 5175 – Université de Montpellier.

Australia

  • Robert Harcourt, MPRG (Marine Predator Research Group), Macquarie University
  • Benjamin Pitcher, MPRG (Marine Predator Research Group), Macquarie University & Taronga Conservation Society Australia, Sydney.

Acoustic recording of an Australian sea lion mother (credit: I. Charrier)

Collection of scent samples on Australian sea lion pup (credit: K. Wierucka)

Behavioural observations of Australian sea lion male (credit: I. Charrier)