Caroline Eozenou - Gamete interaction: from fertilization to contraception
Fertilization is the initial stage of development. Its complex process is finely regulated by dozens of oocyte and sperm genes, some of which are already known and studied. Although most of the various stages have been identified, the players and molecular mechanisms governing gamete fusion remain unknown to this day. Researchers in this field are attempting to unravel the mysteries of fertilization by studying the molecular players in this process. The proteins JUNO and CD9 in the oocyte and IZUMO1 in the sperm have been identified as key players in the adhesion and fusion stages of fertilization. These players have been identified in the context of gamete membrane adhesion, but nothing is known about the fusion step itself. This lack of knowledge (and that of other mechanisms) probably helps to explain the lack of innovation in contraception. Contraceptive pills contain hormones that block ovulation. Numerous side effects have been described in the literature, placing the mental burden of contraception on women. To change this paradigm, we need to change targets. Actors of gametic fusion seem to be ideally suited to these new contraceptive targets. My research questioning is articulated in two complementary axes.
- How do gametes fuse? What are the molecular interactions (cis and trans) leading to gamete fusion? In parallel, I will explore the proteome of the oocyte and sperm (human, murine) during their maturation and then study in greater detail the interactomes of JUNO and CD9 deciphering the oocyte protein complex essential for fertilization.
- What new method(s) of contraception can be developed, based on our current knowledge of gamete interaction? Nanobodies are small antibodies that are highly specific to their epitopes and have blocking properties as well as computationally designed minibinders, I will study the non-hormonal contraceptive power of anti-JUNO and -IZUMO1 nanobodies and minibinders in humans.
These two complementary initiatives aim to improve reproductive health by improving fertility and contraception.
Suzanne Faure-Dupuy - Deciphering the role of resident macrophages in viral pathogenesis
Diseases caused by orthoflaviviruses, such as yellow fever virus, are becoming an increasing threat in Europe due to the expanded populations of their mosquito vectors. Despite the high global burden of these viruses, the interactions of yellow fever virus on host immune responses and how these affect disease outcomes are poorly understood. Resident macrophages are crucial immune cells as they form the first line of defense against pathogens. However, viruses may hijack macrophage function to facilitate both the establishment and the persistence of infection as well as the development of virus-induced pathogenesis. While the exact role of macrophages in yellow fever virus infection and associated pathologies is not fully understood, it is hypothesized that they may contribute to disease progression, particularly in inflammation-related conditions. A significant challenge in studying macrophage function is the lack of robust human models that accurately mimic resident macrophage physiology. With this project, I will take initial steps toward elucidating the fundamental biology of macrophage-yellow fever virus interactions and their contribution to virus-induced pathogenesis. My objectives are: 1) To develop a novel model for studying yellow fever virus effects on resident macrophages; 2) To investigate how yellow fever virus influence macrophage phenotypes and functions; 3) To examine the impact of yellow fever virus-induced modulation of macrophages during the progression of viral pathogenesis.
Clotilde Cadart - Polyploidy and energetics: from cells to Xenopus embryos
Although polyploidization is frequent in development, cancer, and evolution, impacts on animal metabolism are poorly understood. We generated triploid Xenopus laevis embryos and showed that triploid tadpoles are made of fewer, larger cells than diploids and consume oxygen at a lower rate. To understand the underlying basis of such decrease, we optimized quantitative measurements of the energy allocated to proliferation, growth, and maintenance in tadpoles. Results show that the increase in cell size in triploids causes a decrease in total cell surface area and a reduction of costs associated with production and activity at the plasma membrane which explains the overall lower metabolic rate. Crucially, comparison of three Xenopus species that evolved through polyploidization reveals that metabolic differences emerge in development only once cell size scales with genome size. Thus, cell size increase, not ploidy or genome size, causes the reduction in embryo metabolic rate. Ongoing work in my lab is now focusing on investigating the link between ploidy and cellular energetics and energy allocation throughout development.
