MOLECULAR AND CELL BIOLOGY OF ANIMALS
Spyridon Agathos, Georges Bastin, Cathy Debier, Isabelle Donnay, Patrick Dumont, Françoise Gofflot, Bernard Knoops, Yvan Larondelle, Marc Meurens, André Moens, Jean- François Rees, Brigitte Reusens, René Rezsohazy, Yves-Jacques Schneider, and Philippe Van Den Bosch De Aguilar
Mechanisms of mammalian development
I. Donnay, F. Gofflot, A. Moens, C. Remacle, B. Reusens, and R. Rezsohazy
Programs of development
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Mammalian development arises from patterning and differentiation processes controlled by genetic programs onto which environmental cues can impinge.
Several research projects aim to characterize molecular players at work to control the very first steps of embryonic development, from fertilization to early embryonic patterning.
In that context distinct mammalian models (mouse, cattle) are studied to unravel the common grounds or species specific rules of developmental controls.
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Late functions of developmental genes
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Many genes implicated in patterning and differentiation processes during mammalian development are essential for embryonic survival, which has precluded the analysis of their roles in the adult.
Recent findings have shown that for some of these genes the expression continues into adulthood, but few data are available regarding their role and their potential implication in pathogenesis and tumorigenesis.
Two research projects aim to investigate the late function of developmental genes, mainly Hox genes, in the regulation of brain function and in the genesis of mammary tumours.
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Fetal programming of organ activity
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The growth and the development of the mammalian fetus are complex processes primarily organized by its genetic potential which is however strongly influenced by the intra-uterine environment.
Any disturbance in the metabolic fetal environment as it may occur in case of maternal malnutrition may program organs and favor diseases later in life, as revealed by epidemiological and experimental studies focusing on metabolic syndrome including diabetes, obesity, hypertension and cardiovascular diseases.
Our area of research investigated the link between maternal diet and fetal development. In collaboration with Bernard Knoops, our research investigation also involved the development of the antioxidant defense and its programming.
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In vitro production of bovine embryos
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In vitro production of bovine embryos can be used in breeding programmes or in order to save the genetics of infertile valuable cows. It also represents an ideal tool for basic research on gamete interaction and early embryo development in mammals. However, the whole process of in vitro production of embryos still requires optimization.
Current investigations aim to delineate parameters influencing embryo quality, developmental kinetics and resistance to cryoconservation.
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Molecular mechanisms of antioxidative defence
B. Knoops and J.- F. Rees
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In cells and organisms that have evolved to live in aerobic environments, the incomplete reduction of oxygen generates reactive oxygen species. Animal cells have developed complex antioxidant mechanisms to protect themselves against deleterious oxidative attacks but also to control the redox balance implicated in signalling.
Our research work aims at characterizing antioxidant mechanisms that have evolved from invertebrates to mammals with a particular focus on the evolutionary conserved enzymes of the peroxiredoxin family and their associated thioredoxin systems.
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Deep sea fauna
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In an evolutionary perspective, a special emphasis is given to the antioxidant arsenal of pelagic and demersal deep-sea fishes as well as of the marine fauna occurring at hydrothermal vents. In the first case, animals are naturally exposed to low oxidative stress.
Our objective is then to study the antioxidative mechanisms in relationship with animals respiratory activity and the accumulation of high organochlorine levels in their tissues. On the opposite, hydrothermal organisms are exposed to specific chemical environments promoting redox processes in animals and their medium. Our goal is then to characterise the variety of antioxidative machineries, including peroxiredoxins.
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Nutritional quality and chemical safety of foods
C. Debier, M. Meurens, Y. Larondelle, and Y.-J. Schneider
Fatty acids in cow milk and fish flesh
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Fatty acids composition critically contributes to the nutritional quality of food. Ruminant milk fat has been regarded as relatively undesirable in our diet, because of its high content in cholesterol and saturated fat. In contrast, fishes are known to be the best dietary source of omega-3 fatty acids. In both cases however, fatty acids composition and food quality is influenced by the feeding regimen and/or animal breed and species.
In that context, our research aims at understanding what determines the nutritional quality of fats. We therefore also investigate how distinct fatty acids are metabolized by the intestinal epithelium and impact on its physiology.
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Accumulation of food contaminants
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Food contaminants of microbial (mycotoxins) or chemical (organic pollutants) origin provoke severe disorders including intestinal inflammation and perturb intestinal absorption. In contrast, other food compounds, e.g. polyphenols, improve gut health.
Several interconnected projects aim at assessing the risks/benefits of such compounds on the human intestinal function. Using cell culture systems, the effects of mycotoxins, pesticides, heavy metals, but also of polyphenols and some fatty acids are investigated at the cellular and molecular levels on different parameters of the human intestinal function, including in particular inflammation, biotransformation and efflux activities.
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Under-exploited foods resources
A last area of research pursued on food and health concerns new investigations on poorly characterized food resources from the developing countries.
Cell bioengineering
S. Agathos , G. Bastin, and Y.-J. Schneider
Bioreactors
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Increasing demand for therapeutic proteins with correct post-translational modifications has led to the development of animal cell biotechnologies. In that regard, our general objective is to develop industrially relevant culture systems of insect and mammalian cells for the production of therapeutic-grade glycoproteins in high yield and consistent structural quality.
A first approach consists in the scale-up and bioreactor-based optimization of the Baculovirus Expression Vector System (BEVS) which uses lepidopteran insect cells infected with a recombinant lytic insect virus coding for the protein of interest.
Mammalian expression systems such as Chinese Hamster Ovary (CHO) cells stably transformed to secrete glycoproteins have been adapted to serum- and protein-free nutritive media. The addition of vegetal peptones improves cell growth and productivity, as well as glycoprotein quality. Research is now focused to isolate the bioactive molecules and to understand their mode of action on cell physiology.
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Metabolic fluxes and differentiation potential
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In addition to the kinetics and physiology of bioreactor cultivation, animal cells are also studied from a systems biology viewpoint, in order to analyse and exploit their network of metabolic fluxes and differentiation potential.
In particular one important goal of this approach is to assure the propagation and differentiation of animal embryonic stem cells or adult mesenchymal progenitor cells in a single well-controlled scaleable bioreactor. |