1990/95: PhD in Biomedical Sciences (supervisor: P. Michels) UCL, Belgium,
1995/00: Postdoctoral fellow (supervisor: K. Gull) Manchester University, United Kingdom
2001/03: Postdoctoral fellow (supervisor: P. Bastin) USM503, Muséum National d'Histoire Naturelle, Paris.
2004-now: Lecturer MNHN, UMR7245, MNHN/CNRS, team BAMEE
2010: Habilitiation à Diriger des Recherches , Université Pierre et Marie Curie, Paris
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). 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.
- Institut Pasteur, Unit ‘Cell biology of Trypanosomes' - Dr Philippe Bastin.
- Université de Bayreuth (Allemagne) – Dr Klaus Ersfeld.
- Université de Bordeaux – Dr. Derrick Robinson.
- Laboratoire de Biologie du Développement de Villefranche sur mer (UMR7009 CNRS/UPMC)
- Imperial College, Londres – Dr S. Marques.
- University of Brasilia (Brazil) – Dr Izabella Bastos.
Publications (from 2000)
Depoix D, Marques SR, Ferguson DJP, Chaouch S, Duguet T, Sinden RE, Grellier P, Kohl L.(2019) Vital role for Plasmodium berghei Kinesin8B in axoneme assembly during male gamete formation and mosquito transmission. Cell Microbiol. 2019 Oct 21:e13121.
Fort C, Bonnefoy S, Kohl L, Bastin P. (2016) Intraflagellar transport is required for the maintenance of the trypanosome flagellum composition but not its length. J Cell Sci.;129(15):3026-41.
Benmerah A, Durand B, Giles RH, Harris T, Kohl L, Laclef C, Meilhac SM, Mitchison HM, Pedersen LB, Roepman R, Swoboda P, Ueffing M, Bastin P. (2015) The more we know, the more we have to discover: an exciting future for understanding cilia and ciliopathies. Cilia. Mar 31;4:5.
Gallet C, Demonchy R, Koppel C, Grellier P, Kohl L. (2013) A Protein Phosphatase 1 involved in correct nucleus positioning in trypanosomes. Mol Biochem Parasitol. 2013 Nov-Dec;192(1-2):49-54.
Travers MA, Florent I, Kohl L, Grellier P. (2011) Probiotics for the control of parasites: an overview. J Parasitol Res. 2011:610769. Review
Marande W, Kohl L. (2011) Flagellar kinesins in protists. Future Microbiol. 6(2):231-46. Invited Review
Berg M, Kohl L, Van der Veken P (2010) Evaluation of nucleoside hydrolase inhibitors in the treatment of African trypanosomiasis. Antimicrob Agents Chemother, 54, 1900-8.
Demonchy R, Blisnick T, Deprez C, Toutirais G, Loussert C, Marande W, Grellier P, Bastin P, Kohl L. (2009) Kinesin 9 family members perform separate functions in the trypanosome flagellum. J. Cell Biol, 187(5), 615-622.
Depoix D, Kohl L, Florent I. (2008) L’analyse fonctionnelle des gènes chez les protozoaires parasites. Biofutur, 289 : 46-51. Revue
Absalon S, Blisnick T, Bonhivers M, Kohl L, et al. (2008) Flagellum elongation is required for correct structure, orientation and function of the flagellar pocket in Trypanosoma brucei. J. Cell Sci. 121:3704-16 + front cover.
Absalon S, Blisnick T, Kohl L, Toutirais G, et al. (2008). Intraflagellar transport and functional analysis of genes required for flagellum formation in trypanosomes. Mol Biol Cell. 19(3):929-944.
Vaughan S*, Kohl L*, Ngai I, Wheeler RJ, Gull K. (2008). A repetitive protein essential for the flagellum attachment zone filament structure and function in Trypanosoma brucei. Protist. 159(1): 127-36. *equal co-autors
Absalon S*, Kohl L*, Branche C, Blisnick T, et al. (2007). Basal body positioning is controlled by flagellum formation in Trypanosoma brucei. PLoS ONE. May 9; 2(5):e437. *equal co-autors
Branche C, Kohl L, Toutirais G, Buisson J, Cosson J, Bastin P. (2006) Conserved and specific functions of axoneme components in trypanosome motility. J Cell Sci. 119 3443-55.
Kohl L., Robinson D.R. & P. Bastin (2003). Novel roles for the flagellum in cell morphogenesis and cytokinesis of trypanosomes. EMBO J. 22, 5336-46 + front cover.
Durand-Dubief M., Kohl L. & Bastin P. (2003). Efficiency and specificity of RNA interference generated by intra- and intermolecular double stranded RNA in Trypanosoma brucei. Mol. Biochem. Parasitol. 129, 11-21.
Moreira-Leite F.F., Sherwin T., Kohl L. & Gull, K. (2001). A trypanosome structure involved in transmitting cytoplasmic information during cell division. Science, 294, 610-612.
Bastin P., Ellis K., Kohl L. & Gull, K. (2000). Flagellum ontogeny in trypanosomes studied via an inherited and regulated RNA interference system. J Cell Sci. 113, 3321-332
Responsabilities et collective activities
Responsabilities in the MCAM unit
- 2009-… : Evacuation guide of the building 52 (61, rue Buffon, MNHN)
- 2012-2017: Co-editor of MCAM-news ( internal unit magazine, published every 3 month)
- 2015-…: Webmaster for the BAMEE team web site
- Expert for ECOS-Sud , FWO (Research Foundation Flanders, Belgique), BBSRC (Biotechnology and Biological Sciences Research Council, Grande-Bretagne)
- Reviewer for international scientific journals: ‘Experimental Parasitology', ‘Biochimica et Biophysica Acta - Molecular Cell Research', ‘PLoS One'
- Membre of the GDR Cils
- 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 (2008-2012)
- Appointed member of the Section 27 (Host Pathogen Interactions, Immunity and Inflammation) of the CNRS (2012-2016)
- Representative of the doctoral school ED227 (2015 - 2018)
- 2012 - … : In charge of UDV7 : Workshop “Targeting of a gene by RNAi and functional consequences” (Master 2, MNHN, Université Pierre et Marie Curie et Université Paris Diderot)
- 2012 - … : Master M1: TC5 “Comparative Anatomy: adaptation and evolution of anatomical structures from animals and plants” (Motility of unicellular organisms)
- 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 ”
- Raphaël DEMONCHY (2006-2008).
- Luz IRAZAZABAL (Co-supervision with Dr. I. Bastos, University of Brasilia, , 2012)
- Estelle REMION (Co-supervision with Dr. C. Martin, 2017-...)
- 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 : Dr. Carla Nunes de Araujo, University of Brasilia, Brazil
Etudiants en thèse étrangère ou en Master 2
- Maya BERG (2007, 4 month training period, PhD from the Antwerp University, Belgium)
- Luz IRAZAZABAL (2011, Master 2)
- 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) : 10 students from 2010