Institut de Biosciences et Biotechnologies d'Aix-Marseille
Les recherches pluridisciplinaires de l'IBEB s’appuient sur deux plateformes: HélioBiotec pour la biotechnologie des microalgues et Phytotec, labélisée IBISA, pour les expérimentations végétales en conditions contrôlées.
Le service de Cadarache bénéficie également d'un plateau technique en imagerie, ZOOM.
Energies | Energies renouvelables | Bioénergies | Biocarburants | Biohydrogène | Microalgues | Photosynthèse
Chercheur CEA (PhD, HDR)
Biosciences and Biotechnologies Institute of Aix-Marseille CEA/CNRS/Aix-Marseille University, France
Tel: 33-442254651; Fax: 33-442256265; Email:
Lab home page:
2009-present: Senior Scientist. The French Alternative Energies and Atomic Energy Commission (CEA Cadarache), France
2008-2009: Associate Researcher. The French National Center for Scientific Reseach (CNRS), Bordeaux, France
2003-2008: Postdoc Fellow. The laboratory of Professor John Ohlrogge, Michigan State University, USA
2002-2003: Postdoc fellow. Department of Plant Biology, University of Oxford, England
Jan 2002: PhD thesis. The laboratory of Professor Colin Ratledge, University of Hull, England
Oct 2012: HDR (Habilitation à Diriger la Recherche), Aix Marseille University, France
Lipid biology and biotechnology in green photosynthetic cells (microalgae and higher plants). We focus on study of various aspects of lipid metabolism, including fatty acid synthesis, modification, turnover, their acylation to glycerolipids, the regulation of membrane lipid homeostasis and triacylglycerol synthesis and storage - the biogenesis, composition and function of lipid droplets. We explore how to make use of the knowledge generated to re-orient or create new pathways, for production of commercially desirable and lipid-derived compounds from microalgae. To this goal, we have developed and applied a range of tools including algal molecular genetics, high-throughput screening, lipidomics, proteomics, transcriptomics, imaging, and biochemical approaches.
Fatty acids and lipids are synthesized by all cell types. Besides their role as a major form of carbon and energy storage, fatty acids are basic building blocks of biological membranes, part of cellular signaling network, form protective outer envelopes. Research on lipids is both fundamental and applied. From a biotechnological point of view, lipids are essential part of our diet, source of chemical feedstocks, and a major player as a renewable fuel.
Oil is the most reduced form of energy found in nature, and represents twice more energy per gram dry biomass than other storage compounds (starch or protein). Oil (= triacylglycerols), as the name implies, is composed of three often different fatty acids which are esterified to the 3 hydroxyl groups of a glycerol backbone (Figure 1). Function and chemical properties of the oil are conferred largely by the structure of the fatty acids present. Many thousands of fatty acid structures occur in nature (PhyloFA:
https://phylofadb.bch.msu.edu/). They differ in the total number of carbon, degree of unsaturation, with or without further fatty acid modification (for example, hydroxylation, epoxidation, dicarboxylation etc).
Current production of lipids to meet diet and industrial applications is far from sufficient. Novel sources with desirable product in large amount and easily extractable format are highly needed. A more specific problem to lipid production from microalgal strains is the observation that conditions favoring high oil accumulation often result in an arrest in cell growth and biomass production (Figure 2).
As a first step toward understanding oil accumulation in
Chlamydomonas reinhardtii, we followed the changes in cell morphology, chlorophyll, starch and lipid (membrane and storage) content over time. Upon removal of nitrogen from the media, the appearance of cellular oil droplet and starch granules is coincident with the disappearance of chlorophyll and thylakoid membranes. The stored oil are rapidly degraded upon nitrogen re-availability (Figure 4). The molecular mechanisms of the accumulation and degradation of oil are poorly understood, which is one of the current focus of our group. Results obtained down this line should yield important insights into the lipid homeostasis and therefore the overall fitness of cells.
Lipid droplet are subcellular compartment where neutral lipids are stored. It is ubiquitous in all eukaryotes. Other names for this cellular compartment are oil bodies or oleosomes. LDs are spherical organelles consisting of a neutral lipid core enclosed by a membrane lipid monolayer coated with proteins. Until fair recently, LDs are considered only as an energy and carbon storage site. Modern mass spectrometry has revealed the presence of many proteins in the isolated LD fraction. Well characterized structural proteins of oil droplet include oleosins found in oilseeds, or perilipin in adipocytes.
Using mass spectrometry on purified LDs from Chlamydomonas cells starved for nitrogen, our lab together with several other labs have identified a novel structural protein of algal lipid droplets – named Major Lipid Droplet Protein (MLDP). Besides this protein, numerous metabolic enzymes or lipid trafficking proteins are also present for example acyl activating enzymes, acyltransferases or lipases. The enzymes present span the key steps of the triacylglycerol synthesis pathway and including a glycerol-3-phosphate acyltransferase (GPAT), a lysophosphatidic acid acyltransferase (LPAT) and a putative phospholipid:diacylglycerol acyltransferase (PDAT) (Figure 5).
Furthermore, we have more recently provided proteomic, lipidomic and microscopic evidence that cells accumulate different populations of LDs when subjected to high light exposure as compared to the well-studied N starvation (Figure 6). These work highlight the dynamic nature and the role of LDs in relation to the physiological adaptations of algal cells to their environment.
Lipid droplets are now believed to be not only the storage compartments (sink) but also are dynamic structures (node) likely to be involved in processes such as oil synthesis, degradation and lipid homeostasis. Detailed characterization of these LD associated proteins should yield important insight into the compartmentalization and the function and biogenesis of LDs in algae.
Furthermore, lipid droplets are often found to be physically associated to other subcellular organelles such as chloroplast, peroxisome, or mitochondria. Understanding of the energy trafficking pathways, or metabolite shuttles between these organelles should have significant impact not only on the understanding of the subcellular organization of metabolic pathways and their controls, but also on cell physiology, fitness and production of energy dense molecules such as lipids.
Most of our current knowledge on oil synthesis in algae is deduced from plant pathways based on comparative genomics or sequence homologies. Few proteins of lipid metabolisms have been characterizes so far. To reveal novel players of oil metabolism in algae, we have set up two forward genetic screens (Figure 7). Chlamydomonas is a unicellular microalga and most of its life cycle stays as haploid. Generation of mutants is therefore a very powerful approach because the mutant phenotype can be seen in the first generation. Several methods of high throughput screening have been set up (Nile Red neutral lipid staining coupled with flow cytometer, cell counter and HP-TLC; direct transmethylation and GC-FID). Screening of mutants with one of the following phenotypes have been carried out:
Four sets of mutants have been isolated: and some are shown to be altered in the fatty acid composition, some can accumulate significant amount of oil during optimal growth (Figure 8), and we have very lately shown that strains with an attenuated β-oxidation cycle accumulated more oil than WT (Figure 9).
We have in the meantime, initiated some work on the engineering of oil content or composition in Chlamydomonas through gene expression in the plastid genome. In collaboration with the laboratory of Professor Youngsook Lee (Postech, South Korea), we have recently shown that cellular oil content can be increased by 20% when a plastidial LPAT is overexpressed in the plastid genome (Figure 10).
(* corresponding author) Published under either the name of Li or Li-BeissonORCID:
Invited departmental seminars:
Contributed talks at international meetings:
SignauxBioNRJ (2016-2020) - «Manipulating energy signaling to improve biofuel production in photosynthetic eukaryotes » Coordinator: Benoit Menand, Ben Field (CNRS, Marseille) ANR Programme Bioenergies
DIESALG (2012-2015) – « Biodiesel production by microalgae»
Coordinator : Jérémy Pruvost (GEPEA, Nantes) ANR Programme Bio-matières et Energies
NannoControl (2012-2015) “Development of molecular tools for the control of the expression of genes (knockout of native genes, constitutive or promoter-dependent expression of transgenes) in
Nannochloropsis species” Coordinator: Yonghua Li-Beisson (iBEB), Giovanni Finazzi (iRTSV/LPCV) Programme Interne du CEA
Teach « Lipid Metabolism and Lipid Biotechnology » 4 h per year: in the module «
Plants, Energy and Light » for Master level at the University of Aix Marseille, France.
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Acteur majeur de la recherche, du développement et de l'innovation, le CEA intervient dans quatre grands domaines : énergies bas carbone, défense et sécurité, technologies pour l’information et technologies pour la santé.