Our research axes

Principal Investigator: Marjorie Whitfield, CRCN Inserm

Funding : ANR DIVERCIL. Main collaborations : Pr B. Durand (Université de Lyon, France) & Dr Anu Sironen (UCL, London, UK).

Cilia are evolutionary conserved organelles that extend as single or multiple entities at the surface of nearly all cell types of the body. In humans, their structural and/or functional defects are associated with a growing number of inherited disorders, called ciliopathies. Their amazing characteristic is the manifestation of a broad range of symptoms going from chronic respiratory infections to cystic kidneys, obesity, diabetes, retinal degeneration, mental retardation and infertility. Although cilia share a core microtubule-based architecture, stunning variations of their organization exist between organisms or cell types. Their diversity is emphasized in mammals when comparing the flagellum of sperm cells to that of primary cilia found on many cell types. In this context, our laboratory initially investigated the role of the annulus, a peculiar ring-shaped structure surrounding the axoneme, which migrates during flagella assembly and which function remains virtually undefined. Our lab has recently provided novel information regarding the annulus and established several in vivo mouse models to investigate its function. Based on those recent findings, our current work combines cell biology, biochemistry, proteomics and mouse genetics with the aim of deciphering the precise functions and molecular mechanisms of the annulus in sperm flagella assembly.

Principal Investigators: Violaine Simon, MCF & Aminata Touré, DR CNRS

Funding: ANR SPERMetabo, UGA-IRGA. Main collaborations : Dr C. Prip-Buus (Institut Cochin, Paris, France), Marie-Odile Fauvarque (CEA Grenoble, France), Pr Ursula Seidler (Hannover medical School, Germany)

In mammals, sperm cells produced within the testis are structurally differentiated but remain immotile and are unable to fertilize the oocyte unless they undergo a series of maturation events during their transit through the male and female genital tracts. This post-testicular functional maturation is tightly controlled by the ion content, pH, and nutrient availability. In particular, ion fluxes play an essential role in controlling sperm motility and capacitation within the female genital tract. Our group was pioneer in investigating the functions of SLC26 transmembrane anion exchangers in sperm cells and showed their importance for activation of the cAMP-PKA pathway in cooperation with the CFTR channel. Overall, our work indicates that SLC26 channels constitute important regulators of anion fluxes in the processes of sperm maturation and activation. Our current work aims at: i.) further characterizing the downstream signaling pathways and regulators involved in these processes by focusing on both ion channels and other sperm receptors, ii.) investigating the specific features of energy metabolic pathways in sperm cells, and iii.) identifying modulators targeting these signalling pathways.

Responsable de projet: Aminata Touré, DR CNRS

Financement: ANR FLAGELOME. Collaborations principales : Pr P. Ray (CHUGA, France), Dr E. Dulioust/Pr C. Patrat (APHP Cochin, France)  

L'asthénozoospermie, définie par l'absence ou la réduction de la motilité des spermatozoïdes, est induite par des défauts structurels du flagelle des spermatozoïdes et/ou des altérations fonctionnelles qui altèrent le battement flagellaire et la progression des spermatozoïdes. Cette affection est observée chez près de 80 % des hommes infertiles mais les causes génétiques et les mécanismes physiopathologiques associés sont encore mal définis. Notre laboratoire a réalisé des avancées majeures dans la définition génétique de l'asthénozoospermie humaine. En collaboration avec des médecins et des généticiens, notre groupe a contribué à l'identification d'une dizaine de gènes porteurs de mutations responsables de l'asthénozoospermie due à des anomalies morphologiques sévères du flagelle (phénotype MMAF) ; ceci, dans le cadre de l'infertilité masculine isolée ou syndromique (i.e., Primaire dyskinésie ciliaire, ciliopathies). Fait important, notre groupe a également identifié des causes de l'asthénozoospermie humaine due à des défauts majoritairement fonctionnels des spermatozoïdes (SLC26A8, SLC9C1). Nos travaux actuels se concentrent sur la caractérisation fonctionnelle de nouveaux gènes identifiés afin de fournir des connaissances supplémentaires sur les mécanismes moléculaires nécessaires à la bonne motilité des spermatozoïdes et pouvoir développer de nouvelles stratégies thérapeutiques et contraceptives.