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Prof Antoine-Emmanuel Saliba

Single-cell Analysis

Our research and approach

The research group led by Emmanuel Saliba explores host-pathogen interactions in high resolution at the single-cell level. They develop and integrate single-cell genomics, imaging and computational approaches to decipher the microenvironments of individual pathogens and shed light on the heterogeneity of host responses and disease outcomes.

Novel technological leaps are enabling scientists to chart a comprehensive map of the cells across the body, to define their states and to determine their responses to infectious agents in unprecedented detail. Yet how a host either contains the spread of a pathogen, or subsets of pathogens escape host immune surveillance still remains poorly understood.

Emmanuel Saliba’s group investigates RNA and RNA processing as a read-out to determine the cell state of both hosts and pathogens at the single-cell level. Their work, involving pathogens such as Salmonella and respiratory viruses with cell culture models, organoids, and clinical samples, analyses, categorizes and clusters cells to decipher cellular microenvironments and understand infectious disease progression.

They employ single-cell RNA seq, spatial transcriptomics, and RNA imaging to capture the RNA transcript census expressed within a host and pathogen. Further temporal single-cell analysis using RNA metabolic labelling provides insights into the history of a cell. These high-resolution analyses potentially enable the prediction of cell behavior and can unlock gene regulatory networks underlying infectious processes. This work is key in the development of precision diagnostics and therapeutics.

Team members

Research projects

Persistent bacterial infections are caused by a minor subpopulation of intracellular pathogens, called ‘persisters’, that reside in different cell types and tissue locations for years asymptomatically. These subpopulations establish a specific cellular organization, which enables them to evade immune surveillance and chemotherapeutic treatment. Histological studies have described complex tissue remodelling during the infection and emerging in vivo studies at the single-cell level have begun to reveal the heterogeneity of infection foci. 

However, the cellular architecture of the infection foci and the identification of favoured niches within this complex tissue landscape that impact disease outcome remain open questions. For example, Salmonella are believed to reside in a large variety of cells including macrophages, neutrophils, dendritic cells and epithelial cells. These large cell types exist as a myriad of different sub-classes, which were - until recently - not appreciated. Similarly, within an infected tissue such as the spleen many infected cells escape inflammatory lesions and disseminate into tissues. Therefore, single-cell studies in an in vivo context are necessary to understand the heterogeneity inherent in infected cells, their microenvironment and their function. The Single-cell Analysis group develops and combines in vitro and in vivo single-cell transcriptomics to decipher the cellular organization of infection foci and their functional consequences for infection outcome.

The recent emergence of single-cell genome-wide transcriptomics is proving to be a powerful approach to decipher both cellular identities and function making it possible to study heterogeneity. This is being facilitated by the development of automated platforms that enable the processing of hundreds and thousands of single-cells in parallel. In the context of infection we have pioneered the use of single-cell RNA-seq to investigate heterogeneity in the response of mouse bone marrow-derived macrophages to Salmonella focusing on bacteria with different growth status including non-growing ‘persisters’ that have been linked to recurrent infections. We have described how Salmonella impact the wide spectrum of host polarization and revealed the existence of a subset of macrophages that escape inflammatory and immune activation programs. While providing new insights into the host response, the study was limited to analyzing infected cells from in vitro cultures. The next step is now to decipher the response of single cells of infected tissues, which remains an unmet challenge.

Moreover, the Single-cell Analysis group is fully committed to developing the full potential of single-cell RNA-seq for addressing fundamental scientific questions of infection biology in general, at the HIRI as well as at other locations of the HZI.

In focus

COVID-19-related respiratory failure: Why patients require prolonged ventilation

The majority of patients with severe COVID-19 develop unusually pronounced scarring of the lungs. In a joint study published in Cell, scientists from the Saliba lab and other German research sites report that macrophages — immune cells which engulf and digest foreign substances — play a central role in this regard. Some of the mechanisms involved in COVID-19-related respiratory failure resemble those seen in idiopathic pulmonary fibrosis, a previously incurable disease which causes scarring of the lungs. Misguided wound healing responses resulting in scarring may explain why COVID-19 patients remain in respiratory failure for so long, and why they require prolonged extracorporeal membrane oxygenation (ECMO) support.

Publications

2023

Circulating NK cells establish tissue residency upon acute infection of skin and mediate accelerated effector responses to secondary infection

Torcellan T, Friedrich C, Doucet-Ladevèze R, Ossner T, Solé VV, Riedmann S, Ugur M, Imdahl F, Rosshart SP, Arnold SJ, …, Kastenmüller W, Gasteiger G (2023)

Immunity (Online ahead of print)

Sequential Antigen-loss and Branching Evolution in Lymphoma after CD19- and CD20-Targeted T-cell Redirecting Therapy

Duell J, Leipold AM, Appenzeller S, Fuhr V, Rauert-Wunderlich H, Da Vià MC, Dietrich O, Toussaint C, Imdahl F, Eisele F, …, Saliba AE, Rasche L (2023)

Blood (Online ahead of print)

Brain-to-gut trafficking of alpha-synuclein by CD11c+ cells in a mouse model of Parkinson's disease

McFleder RL, Makhotkina A, Groh J, Keber U, Imdahl F, Peña Mosca J, Peteranderl A, Wu J, Tabuchi S, Hoffmann J, …, Volkmann J, Ip CW (2023)

Nature Communications 14 (1): 7529

Vector-borne Trypanosoma brucei parasites develop in artificial human skin and persist as skin tissue forms

Reuter C, Hauf L, Imdahl F, Sen R, Vafadarnejad E, Fey P, Finger T, Jones NG, Walles H, Barquist L, …, Groeber-Becker F, Engstler M (2023)

Nature Communications 14 (1): 7660

Microglia-mediated demyelination protects against CD8+ T cell-driven axon degeneration in mice carrying PLP defects

Groh J, Abdelwahab T, Kattimani Y, Hörner M, Loserth S, Gudi V, Adalbert R, Imdahl F, Saliba AE, Coleman M, …, Simons M, Martini R (2023)

Nature Communications 14 (1): 6911

Th17.1 cell driven sarcoidosis-like inflammation after anti-BCMA CAR T cells in multiple myeloma

Leipold AM, Werner RA, Düll J, Jung P, John M, Stanojkovska E, Zhou X, Hornburger H, Ruckdeschel A, Dietrich O, …, Saliba AE, Rasche L (2023)

Leukemia 37 (3): 650-658

Myocardial Milieu Favors Local Differentiation of Regulatory T Cells

Delgobo M, Weiß E, ElDin Ashour D, Richter L, Popiolkowski L, Arampatzi P, Stangl V, Arias-Loza P, Mariotti-Ferrandiz E, Rainer PP, …, Frantz S, Campos Ramos G (2023)

Circulation Research 132 (5): 565-582

Integrated single-cell analysis based classification of vascular mononuclear phagocytes in mouse and human atherosclerosis

Zernecke A, Erhard F, Weinberger T, Schulz C, Ley K, Saliba AE, Cochain C (2023)

Cardiovascular Research 119 (8): 1676-1689

Dynamics of monocyte-derived macrophage diversity in experimental myocardial infarction

Rizzo G, Gropper J, Piollet M, Vafadarnejad E, Rizakou A, Bandi SR, Arampatzi P, Krammer T, DiFabion N, Dietrich O, …, Saliba AE, Cochain C (2023)

Cardiovascular Research 119 (3): 772-785

Rapid neutrophil mobilisation by VCAM-1+ endothelial extracellular vesicles

Akbar N, Braithwaite AT, Corr EM, Koelwyn GJ, van Solingen C, Cochain C, Saliba AE, Corbin A, Pezzolla D, Møller Jørgensen M, …, Melling GE, Shanmuganathan M (2023)

Cardiovascular Research 119 (1): 236-251

Genetic inhibition of CARD9 accelerates the development of atherosclerosis in mice through CD36 dependent-defective autophagy

Zhang Y, Vandestienne M, Lavillegrand JR, Joffre J, Santos-Zas I, Lavelle A, Zhong X, Le Goff W, Guérin M, Al-Rifai R, …, Sokol H, Ait-Oufella H (2023)

Nature Communications 14 (1): 4622

Short-range interactions between fibrocytes and CD8+ T cells in COPD bronchial inflammatory response

Eyraud E, Maurat E, Sac-Epée JM, Henrot P, Zysman M, Esteves P, Trian T, Dupuy JW, Leipold A, Saliba AE, …, Berger P, Dupin I (2023)

eLife 12: RP85875

Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks

Ugur M, Labios RJ, Fenton C, Knöpper K, Jobin K, Imdahl F, Golda G, Hoh K, Grafen A, Kaisho T, …, Bajénoff M, Kastenmüller W (2023)

Immunity 58 (8): 1778-1793.e10

Cytotoxic CNS-associated T cells drive axon degeneration by targeting perturbed oligodendrocytes in PLP1 mutant mice

Abdelwahab T, Stadler D, Knöpper K, Arampatzi P, Saliba AE, Kastenmüller W, Martini R, Groh J (2023)

iScience 26 (5): 106698

An interferon gamma response signature links myocardial aging and immunosenescence

Ashour D, Rebs S, Arampatzi P, Saliba AE, Dudek J, Schulz R, Hofmann U, Frantz S, Cochain C, Streckfuß-Bömeke K, Ramos GC (2023)

Cardiovascular Research (Online ahead of print)

Advancing massive transcriptional profiling of single bacteria

Saliba AE (2023)

Cell Reports Methods 3 (2): 100416

A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection

Däullary T, Imdahl F, Dietrich O, Hepp L, Krammer T, Fey C, Neuhaus W, Metzger M, Vogel J, Westermann AJ, Saliba AE, Zdzieblo D (2023)

Gut Microbes 15 (1): 2186109

Altered and allele-specific open chromatin landscape reveals epigenetic and genetic regulators of innate immunity in COVID-19

Zhang B, Zhang Z, Koeken VACM, Kumar S, Aillaud M, Tsay HC, Liu Z, Kraft ARM, Soon CF, Odak I, …, Schulte LN, Li Y (2023)

Cell Genomics 3 (2): 100232

A MATQ-seq-Based Protocol for Single-Cell RNA-seq in Bacteria

Homberger C, Saliba AE, Vogel J (2023)

Methods in Molecular Biology 2584: 105-121

2022

JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm

Al-Rifai R, Vandestienne M, Lavillegrand JR, Mirault T, Cornebise J, Poisson J, Laurans L, Esposito B, James C, Mansier O, …, Rautou PE, Ait-Oufella H (2022)

Nature Communications 13 (1): 6592

Postnatal expansion of mesenteric lymph node stromal cells towards reticular and CD34+ stromal cell subsets

Pezoldt J, Wiechers C, Zou M, Litovchenko M, Biocanin M, Beckstette M, Sitnik K, Palatella M, van Mierlo G, Chen W, …, Deplancke B, Huehn J (2022)

Nature Communications 13 (1): 7227

Helicobacter pylori shows tropism to gastric differentiated pit cells dependent on urea chemotaxis

Aguilar C, Pauzuolis M, Pompaiah M, Vafadarnejad E, Arampatzi P, Fischer M, Narres D, Neyazi M, Kayisoglu Ö, Sell T, …, Saliba AE, Bartfeld S (2022)

Nature Communications 13 (1): 5878

Fibroblastic reticular cells mitigate acute graft-versus-host disease via MHCII-dependent maintenance of regulatory T cells

Shaikh H, Pezoldt J, Mokhtari Z, Gamboa Vargas J, Le DD, Peña Mosca J, Arellano-Viera E, Kern MA, Graf C, Beyersdorf N, …, Huehn J, Beilhack A (2022)

JCI Insight 7 (22): e154250

Landscape and age dynamics of immune cells in the Egyptian rousette bat

Friedrichs V, Toussaint C, Schäfer A, Rissmann M, Dietrich O, Mettenleiter TC, Pei G, Balkema-Buschmann A, Saliba AE, Dorhoi A (2022)

Cell Reports 40 (10): 111305

Nonproductive exposure of PBMCs to SARS-CoV-2 induces cell-intrinsic innate immune responses

Kazmierski J, Friedmann K, Postmus D, Emanuel J, Fischer C, Jansen J, Richter A, Bosquillon de Jarcy L, Schüler C, Sohn M, …, Niemeyer D, Goffinet C (2022)

Molecular Systems Biology 18 (8): e10961

Lymphatic migration of unconventional T cells promotes site-specific immunity in distinct lymph nodes

Ataide MA, Knöpper K, Cruz de Casas P, Ugur M, Eickhoff S, Zou M, Shaikh H, Trivedi A, Grafen A, Yang T, …, Gasteiger G, Kastenmüller W (2022)

Immunity 55 (10): 1813–1828.e9

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Georg P, Astaburuaga-García R, Bonaguro L, Brumhard S, Michalick L, Lippert LJ, Kostevc T, Gäbel C, Schneider M, Streitz M, …, Sawitzki B, PA-COVID-19 Study Group (2022)

Cell 185 (3): 493-512.e25

Interleukin-23 receptor expressing γδ T cells locally promote early atherosclerotic lesion formation and plaque necrosis in mice

Gil-Pulido J, Amézaga N, Jorgacevic I, Manthey HD, Rösch M, Brand T, Cidlinsky P, Schäfer S, Beilhack A, Saliba AE, …, Cochain C, Zernecke A (2022)

Cardiovascular Research 118 (14): 2932-2945

Time-resolved single-cell RNA-seq using metabolic RNA labelling

Erhard F, Saliba AE, Lusser A (2022)

Nature Reviews Methods Primers 2 (1): 331

Type 1 conventional dendritic cells maintain and guide the differentiation of precursors of exhausted T cells in distinct cellular niches

Dähling S, Mansilla AM, Knöpper K, Grafen A, Utzschneider DT, Ugur M, Whitney PG, Bachem A, Arampatzi P, Imdahl F, …, Bedoui S, Kastenmüller W (2022)

Immunity 55 (4): 656-670.e8

2021

Effector differentiation downstream of lineage commitment in ILC1s is driven by Hobit across tissues

Friedrich C, Taggenbrock RLRE, Doucet-Ladevèze R, Golda G, Moenius R, Arampatzi P, Kragten NAM, Kreymborg K, Gomez de Agüero M, Kastenmüller W, …, van Gisbergen KPJM, Gasteiger G (2021)

Nature Immunology 22 (10): 1256-1267

SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis

Wendisch D, Dietrich O, Mari T, von Stillfried S, Ibarra IL, Mittermaier M, Mache C, Chua RL, Knoll R, Timm S, …, Saliba AE, Sander LE (2021)

Cell 184 (26): 6243-6261.e27

Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma

Da Vià MC, Dietrich O, Truger M, Arampatzi P, Duell J, Heidemeier A, Zhou X, Danhof S, Kraus S, Chatterjee M, …, Saliba AE, Rasche L (2021)

Nature Medicine 27 (4): 616-619

Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia

Chumduri C, Gurumurthy RK, Berger H, Dietrich O, Kumar N, Koster S, Brinkmann V, Hoffmann K, Drabkina M, Arampatzi P, …, Saliba AE, Meyer TF (2021)

Nature Cell Biology 23 (2): 184–197

Dysregulated Immunometabolism Is Associated with the Generation of Myeloid-Derived Suppressor Cells in Staphylococcus aureus Chronic Infection

Dietrich O, Heinz A, Goldmann O, Geffers R, Beineke A, Hiller K, Saliba AE, Medina E (2021)

Journal of Innate Immunity: 1-18

The healing myocardium mobilises a distinct B-cell subset through a CXCL13-CXCR5-dependent mechanism

Heinrichs M, Ashour D, Siegel J, Büchner L, Wedekind G, Heinze KG, Arampatzi P, Saliba AE, Cochain C, Hofmann U, Frantz S, Campos Ramos G (2021)

Cardiovascular Research 117 (13): 2664-2676

Time-Resolved scRNA-Seq Tracks the Adaptation of a Sensitive MCL Cell Line to Ibrutinib Treatment

Fuhr V, Vafadarnejad E, Dietrich O, Arampatzi P, Riedel A, Saliba AE, Rosenwald A, Rauert-Wunderlich H (2021)

International journal of molecular sciences 22 (5): 2276

Initial HCV infection of adult hepatocytes triggers a temporally structured transcriptional program containing diverse pro- and anti-viral elements

Tegtmeyer B, Vieyres G, Todt D, Lauber C, Ginkel C, Engelmann M, Herrmann M, Pfaller CK, Vondran FW, Broering R, …, Pietschmann T, Brown RJ (2021)

Journal of Virology 95 (10)

A genome-wide transcriptomic analysis of embryos fathered by obese males in a murine model of diet-induced obesity

Bernhardt L, Dittrich M, El-Merahbi R, Saliba AE, Müller T, Sumara G, Vogel J, Nichols-Burns S, Mitchell M, Haaf T, El Hajj N (2021)

Scientific Reports 11: 1979

2020

Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19

Bernardes JP, Mishra N, Tran F, Bahmer T, Best L, Blase JI, Bordoni D, Franzenburg J, Geisen U, Josephs-Spaulding J, …, Schultze JL, Rosenstiel P (2020)

Immunity 53 (6): 1296-1314.e9

Dynamics of Cardiac Neutrophil Diversity in Murine Myocardial Infarction

Vafadarnejad E, Rizzo G, Krampert L, Arampatzi P, Arias-Loza A, Nazzal Y, Rizakou A, Knochenhauer T, Bandi SR, Nugroho VA, …, Saliba AE, Cochain C (2020)

Circulation Research 127 (9): e232-249

LifeTime and improving European healthcare through cell-based interceptive medicine

Rajewsky N, Almouzni G, Gorski SA, Aerts S, Amit I, Bertero MG, Bock C, Bredenoord AL, Cavalli G, Chiocca S, …, Vidal M, Voet T (2020)

Nature 587 (7834): 377-386

Single-cell RNA-sequencing reports growth-condition-specific global transcriptomes of individual bacteria

Imdahl F, Vafadarnejad E, Homberger C, Saliba AE, Vogel J (2020)

Nature Microbiology 5 (10): 1202–1206

Severe COVID-19 is marked by a dysregulated myeloid cell compartment

Schulte-Schrepping J, Reusch N, Paclik D, Baßler K, Schlickeiser S, Zhang B, Krämer B, Krammer T, Brumhard S, Bonaguro L, …, Saliba AE, Sander LE (2020)

Cell 182 (6): 1419-1440

Eleven grand challenges in single-cell data science

Lähnemann D, Köster J, Szczurek E, McCarthy DJ, Hicks SC, Robinson MD, Vallejos CA, Campbell KR, Beerenwinkel N, Mahfouz A, …, Shah SP, Schönhuth A (2020)

Genome Biology 21: 31

Advances and challenges in single-cell RNA-seq of microbial communities

Imdahl F, Saliba A (2020)

Current Opinion in Microbiology 57: 102-110

Tracheal brush cells release acetylcholine in response to bitter tastants for paracrine and autocrine signaling

Hollenhorst MI, Jurastow I, Nandigama R, Appenzeller S, Li L, Vogel J, Wiederhold S, Althaus M, Empting M, Altmüller J, …, Saliba AE, Krasteva-Christ G (2020)

The FASEB Journal 34 (1): 316-332

2019

scSLAM-seq reveals core features of transcription dynamics in single cells

Erhard F, Baptista MA, Krammer T, Hennig T, Lange M, Arampatzi P, Jürges CS, Theis FJ, Saliba AE, Dölken L (2019)

Nature 571 (7765): 419-423

2018

Salmonella persisters undermine host immune defenses during antibiotic treatment

Stapels DA, Hill PW, Westermann AJ, Fisher RA, Thurston TL, Saliba AE, Blommestein I, Vogel J, Helaine S (2018)

Science 362 (6419): 1156-1160

Neonatally imprinted stromal cell subsets induce tolerogenic dendritic cells in mesenteric lymph nodes

Pezoldt J, Pasztoi M, Zou M, Wiechers C, Beckstette M, Thierry GR, Vafadarnejad E, Floess S, Arampatzi P, Buettner M, …, Saliba AE, Huehn J (2018)

Nature Communications 9: 3903

Single-Cell RNA-Seq Reveals the Transcriptional Landscape and Heterogeneity of Aortic Macrophages in Murine Atherosclerosis

Cochain C, Vafadarnejad E, Arampatzi P, Pelisek J, Winkels H, Ley K, Wolf D, Saliba AE, Zernecke A (2018)

Circulation Research 122 (12): 1661-1674

Atlas of the Immune Cell Repertoire in Mouse Atherosclerosis Defined by Single-Cell RNA-Sequencing and Mass Cytometry

Winkels H, Ehinger E, Vassallo M, Buscher K, Dinh HQ, Kobiyama K, Hamers AA, Cochain C, Vafadarnejad E, Saliba AE, …, Ley K, Wolf D (2018)

Circulation Research 122 (12): 1675-1688

Genome organization and DNA accessibility control antigenic variation in trypanosomes

Müller LS, Cosentino RO, Förstner KU, Guizetti J, Wedel C, Kaplan N, Janzen CJ, Arampatzi P, Vogel J, Steinbiss S, …, Sebra RP, Siegel TN (2018)

Nature 563 (7729): 121-125

Tolerogenic Transcriptional Signatures of Steady-State and Pathogen-Induced Dendritic Cells

Vendelova E, Ashour D, Blank P, Erhard F, Saliba AE, Kalinke U, Lutz MB (2018)

Frontiers in Immunology 9: 333

2017

Einzelzell-RNA-Sequenzierung beleuchtet den Infektionsprozess

Saliba AE, Westermann AJ, Vogel J (2017)

BIOspektrum 23 (5): 525-528

New RNA-seq approaches for the study of bacterial pathogens

Saliba AE, Santos SC, Vogel J (2017)

Current Opinion in Microbiology 35: 78-87

2016

A protocol for the systematic and quantitative measurement of protein-lipid interactions using the liposome-microarray-based assay

Saliba AE, Vonkova I, Deghou S, Ceschia S, Tischer C, Kugler KG, Bork P, Ellenberg J, Gavin A (2016)

Nature Protocols 11 (6): 1021-38

Single-cell RNA-seq ties macrophage polarization to growth rate of intracellular Salmonella

Saliba AE, Li L, Westermann AJ, Appenzeller S, Stapels DA, Schulte LN, Helaine S, Vogel J (2016)

Nature Microbiology 2: 16206

2015

The systematic analysis of protein-lipid interactions comes of age

Saliba AE, Vonkova I, Gavin A (2015)

Nature Reviews Molecular Cell Biology 16 (12): 753-61

Lipid Cooperativity as a General Membrane-Recruitment Principle for PH Domains

Vonkova I, Saliba AE, Deghou S, Anand K, Ceschia S, Doerks T, Galih A, Kugler KG, Maeda K, Rybin V, …, Bork P, Gavin A (2015)

Cell Reports 12 (9): 1519-30

2014

A quantitative liposome microarray to systematically characterize protein-lipid interactions

Saliba AE, Vonkova I, Ceschia S, Findlay GM, Maeda K, Tischer C, Deghou S, van Noort V, Bork P, Pawson T, Ellenberg J, Gavin A (2014)

Nature Methods 11 (1): 47-50

Single-cell RNA-seq: advances and future challenges

Saliba AE, Westermann AJ, Gorski SA, Vogel J (2014)

Nucleic Acids Research 42 (14): 8845-60

2010

Microfluidic sorting and multimodal typing of cancer cells in self-assembled magnetic arrays

Saliba AE, Saias L, Psychari E, Minc N, Simon D, Bidard F, Mathiot C, Pierga J, Fraisier V, Salamero J, …, Malaquin L, Viovy J (2010)

PNAS 107 (33): 14524-9

2009

Cellules tumorales circulantes et cancer du sein : méthodes de détection et résultats cliniques

Bidard F, Saliba AE, Saias L, Degeorges A, Cremoux Pd, Viovy J, Vincent-Salomon A, Mathiot C, Pierga J, Gramont A (2009)

Bulletin du Cancer 96 (1): 73-86

2004

Nanotechnology serving biochips – The Toulouse example

Vieu C, Malaquin L, Thibault C, Saliba AE, Daran E, Dildan M, Carcenac F, Leberre V, Trevisiol E, François JM (2004)

Biofutur (250): 41-45