Field of expertise
Trypanosome, cytoskeleton, kinesin, morphogenesis, molecular and cellular microbiology
Kinesins, a toolbox for cell morphogenesis ?
I am interested in the comprehension of the molecular mechanisms governing cell morphogenesis in the protozoan parasite Trypanosoma brucei , the agent of sleeping sickness in human and cattle. In order to survive trypanosomes have to alternate between to hosts, an insect vector – the tsetse fly and a mammalian host. Moreover they pass through different tissues within the hosts (insect midgut and salivary glands, mammalian bloodstream) and they have to adapt to the environmental conditions (temperature, pH, nutriments…). These adaptations are accompanied by specific changes in the surface coat and the metabolism (glycolysis or respiration depending on the life cycle stage) as well as striking morphological changes.
During the cell cycle the parasite also has to replicate its organelles (nucleus, mitochondrion, flagellum, …) and to distribute them between the two daughter cells. Both the morphological changes and the distribution of the organelles require molecular motor proteins, such as kinesins and dyneins. The trypanosome genome contains 58 genes coding for kinesins, a surprisingly large number compared to humans (45 kinesin genes). We propose that this unicellular parasite needs this many kinesins in order to organise its cytoskeleton, predominantly composed of microtubules. To date only a handful of trypanosome kinesins has been characterised and one of my projects is to determine the role(s) of these motor proteins in this fascinating protist.
Cell cycle cellulaire of Trypanosoma brucei (procyclic form). Phase contrast images with DNA labelling (nucleus and kinetoplast) by DAPI (mauve) and flagellar labelling (green). K, kinetoplaste; N, nucleus
© MNHN - Linda Kohl.
I am particularly interested in two groups of kinesins: 1. kinesins which are restricted to trypanosomatids ( T. brucei , T. cruzi , Leishmania ), which could point research activity towards new drug targets and 2. Kinesins involved in formation or function of cilia and flagella, well conserved structured which fulfil many essential roles in eukaryotes. In this case, the trypanosome is used a model organism.
Until now, the general idea was to think that in most eukaryotes all flagellar structures (axoneme and supplementary structures) were built by Intraflagellar transport (IFT). We have recently shown that in the trypanosome an additional specific kinesin (KIF9B) is essential for the assembly of the extra-axonemal structure (the paraflagellar rod, PFR). The absence of this protein causes structural modifications in the PFR as well as motility defects. Moreover these cells die within a few days. Additional flagellar structures can also be found in other organisms, such as outer dense fibers in mammalian spermatozoa. The data obtained in the trypanosome can bring indications for more complicated systems. This work was published in Journal of Cell Biology , Demonchy et al., 2009, 187 (5): 615-22).
Kinesin 9 family member KIF9B only is essential for PFR assembly (from Demonchy et al., 2009.)
Several other kinesins are currently studied and for several of these, preliminary data are encouraging: KIN1 and KIN3 are essential for cell survival and in their absence abnormal cells are seen. KIN5 seems involved in the attachment of the flagellum to the cell body.
Absence of KIN3 causes multinucleated cells in Trypanosoma brucei. Phase contrast images with DNA labelling (nucleus and kinetoplast) by DAPI (mauve) and flagellar labelling (green).© MNHN - Linda Kohl.
Several ongoing projects are realised in collaboration:
Kinesins in Plasmodium (PI: Delphine Depoix, UMR7245)
NudC, a protein potentially involved in mitosis. This project is a comparative study of NudC in T. brucei and Schizosaccharomyces pombe . It was financed by the Convergence program ‘Cycle de la vie', from Sorbonne Universités (collaboration S. Castagnetti, UMR CNRS 7009).
RSP9, an axonemal protein. This comparative project compares RSP9 in Trypanosoma and Plasmodium (collaboration S. Marques, Imperial College, London).
2012-…: In charge of UDV7 : Workshop “Targeting of a gene by RNAi and functional consequences”
2012-…: Master M1: TC5 “Comparative Anatomy: adaptation and evolution of anatomical structures from animals and plants”
2012-2013: Master M2: UDV22: “Functional diversity of Protists”
2012-…: Master M2: UDV4 : “ Diversity and functional biology of et micro-organisms ” – dinoflagellates, amoeba
2012-…: Master M2: Control of gene expression by nucleic acids
2014-…: Master M2: MVE20: “ Biodiversity and Functional Ecology of Microorganisms ”
- Student Supervision:
- PhD students:
Raphaël DEMONCHY (2006-2008). The results from this PhD were published in: Demonchy R, Blisnick T, Deprez C, Toutirais G, Loussert C, Marande W, Grellier P, Bastin P, Kohl L. (2009) J. Cell Biol, 187 (5), 615-622.). M. Demonchy now works at Orphanet INSERM SC11, on rare diseases.
Luz IRAZAZABAL (Co-supervision with Dr. I. Bastos, University of Brasilia, start date march 2012) Functional study of a kinesin specific to Trypanosomatidae as a strategy for the identification of new therapeutic targets against Chagas disease and leishmaniasis. Financing: CNPq from Brasilia.
- Post-doctorate and visiting scientists
2009-2011: W. MARANDE, financed on the ANR SENSOTRYPA contract. M. Marande was recruited at the French Plant Genomic Resource Center in Toulouse.
2014 : 1 year visit of Dr. Carla Nunes de Araujo, Brasilia University, Brazil in the framework of the CAPES-COFECUB and CNPq agreement between the l aboratories ‘Interactions hôtes pathogènes de l'Université de Brasilia (UnB)' and the team BAMEE. Project: The kinetoplastid-specific kinesin 1 from Trypanosoma cruzi and Leishmania braziliensis, agents of Chagas disease and Leishmaniasis. Financing : ATM ‘Les microorganismes, acteurs clés des écosystèmes'.
2016 : 3 week visit of Dr. Carla Nunes de Araujo, Brasilia University, Brazil in the framework of the CAPES-COFECUB and CNPq agreement between the l aboratories ‘Interactions hôtes pathogènes de l'Université de Brasilia (UnB)' and the team BAMEE.
-Foreign PhD and Master M2 students:
Maya BERG (2007, 4 month training period, PhD from the Antwerp University, Belgium). The research accomplished during this period was published in: Berg M, Kohl L , Van der Veken P et al. (2010) Antimicrob Agents Chemother, 54 : 1900-8. Ms Berg is currently working as a postdoc at the Institut for Tropical Medicine Prince Léopold in Antwerp , Belgium.
Luz IRAZAZABAL (2011, Master 2). PhD thesis in co-supervision with Dr. I. Bastos, University of Brasilia.
Cécile PHILIPPOTEAUX (2012, Master 2 & Doctor of Pharmacy, University of Reims).
Lysiane Pao ( M2-Pro – University Paul Sabatier, Toulouse, 2014)
Ons Ben Aissa (M2 University Versailles St Quentin en Yvelines, 2015)
Nour Chamseddine (M2, Rouen University)
Estelle Remion ( M2, EPHE, Paris, 2016)
- Students for short term training periods (Master 1, Graduats, BTS)
Mokhtar MOHAMET (BTS, 2007)
Kévin MELICINE (BTS 2009, 2010 ) .
Stéphanie LUIGGI ( Master 1, 2011 )
Esther AFOUTOU (BTS, 2011, 2012 ).
Fany FANDJOU ( Master 1, 2012 )
Lauriane PETIT (BTS, 2012, 2013)
Eïleen TANIER (BTS, 2013)
Anais Raia (M1, UPMC, 2013)
Guillaume Ha (M1, UPMC, 2014)
Jonathan Dikec (L3, Université Paris Est Créteil, 2015)
Coralie Thorrens (BTS , 2016)
Pasteur Institut, Paris, Unit ‘Cell biology of Trypanosomes' - Dr Philippe Bastin.
Bayreuth University (Germany) – Dr Klaus Ersfeld.
Bordeaux University– Dr. Derrick Robinson.
Developmental Biology Laboratory - Stefania Castagnetti
Imperial College, London – Dr S. Marques.
University of Brasilia (Brazil) – Dr Izabella Bastos.
- 2008-2012: Member of the selection comity of the National Fund for research of the Grand-Duchy of Luxembourg (domain: biology) for the attribution of PhD and post-doctoral fellowships
- 2012-2016: Appointed member of the Section 27 (Host Pathogen Interactions, Immunity and Inflammation) of the CNRS
- 2009-… : Evacuation guide of the building 52 (61, rue Buffon, MNHN)
- 2009-...: In charge of communication of the team ‘Adaptation of protozoa to their environment'
- 2012-2017: Co-editor of MCAM-news ( internal unit magazine, published every 3 month)
- 2013-…: Member of the GDR Cils
- 2015-…: Co-webmaster for the BAMEE team web site
- 2015-…: Representative of the doctoral school ED227
Administrative and scientific responsibilities
- 2009-2012: Scientific and financial management of the project ANR SENSOTRYPA for team 2.
- 2014-2016: Scientific and financial management of the project projet ‘Molecular mechanism of mitosis in unicellular organisms : diversity and evolution of NudC' (Convergence ‘Cycle de la vie') for team 2.
- 2009-...: Expert for ECOS-Sud , FWO (Research Foundation Flanders, Belgique), BBSRC (Biotechnology and Biological Sciences Research Council, Grande-Bretagne)
- 2009-...: Reviewer for international scientific journals: ‘Experimental Parasitology', ‘Biochimica et Biophysica Acta - Molecular Cell Research', ‘PLoS One'
List of publications