Toxoplasma gondii | EPFL Graph Search

Toxoplasma gondii (ˈtɒksəˌplæzmə_ˈɡɒndi.aɪ,_-iː) is a parasitic protozoan (specifically an apicomplexan) that causes toxoplasmosis. Found worldwide, T. gondii is capable of infecting virtually all warm-blooded animals, but felids are the only known definitive hosts in which the parasite may undergo sexual reproduction. In rodents, T. gondii alters behavior in ways that increase the rodents' chances of being preyed upon by felids. Support for this "manipulation hypothesis" stems from studies showing that T. gondii-infected rats have a decreased aversion to cat urine while infection in mice lowers general anxiety, increases explorative behaviors and increases a loss of aversion to predators in general. Because cats are one of the only hosts within which T. gondii can sexually reproduce, such behavioral manipulations are thought to be evolutionary adaptations that increase the parasite's reproductive success since rodents that do not avoid cat habitations will m

Hortus hybridus domestique. Un jardin pour les étudiants d'architecture de l'EPFL

Carole Lesigne

«L'imagination ce n'est pas la création, mais l'intensification des choses existantes». [Hohl, Ludwig] ; Ce projet part du postulat que nos sociétés occidentales traversent actuellement une crise complexe aux tenants et aboutissants sociaux, économiques et écologiques. L'architecte, de part l'impact de ses choix architecturaux sur l'environnement spatial et social, possède la formidable opportunité d'inciser dans la réalité, de soulever le débat et de mettre en mouvement des dynamiques nouvelles. L'hortus hybridus est un jardin hybride qui a été identifié comme possédant le potentiel d'amorcer une réflexion autour de champs aussi divers que la re-création de liens sociaux, la recherche de qualité spatiale au sein de l'espace public, le retour à une culture vivrière et la nécessité de transformer nos modes de vie afin de les adapter à la recherche d'un équilibre écologique. L'installation d'un système d'hortus hybridus au sein de l'EPFL est vue comme une occasion de tester la capacité du jardin à transformer le visage du campus et soulève la question de la qualité de ses espaces extérieurs. S'appuyant sur une observation précise du site qui permet, comme l'énonce Georges Descombes «de trouver les justes motifs d'une intervention», ce projet d'hortus hybridus domestique pour les étudiants d'architecture s'attache à «intensifier certains éléments existants du site» afin de ré-activer des liens entre différents éléments spatiaux et sociaux et de faire revenir à la surface un potentiel oublié, mais latent.

2015

Reconstruction and systems analysis of metabolism in apicomplexan parasites Toxoplasma gondii and Plasmodium falciparum

Stepan Tymoshenko

Understanding of metabolism in disease-causing microorganisms promotes drug design through the identification of the enzymes whose activity is indispensable for important cellular functions of the pathogens. Nowadays such understanding arises from experimental as well as computational studies. These two approaches, long considered as rather orthogonal, in recent years began to converge and form a new field, where they are utilized as complementary. In this thesis I present my endeavors in bringing closer the fields of infection and systems biology with a particular focus on large-scale metabolic models and their analysis. Integrative, interdisciplinary nature of my project also included multiple experimental inputs as well as original experimental efforts on investigating model-derived hypotheses. In the scope of this thesis I explored metabolism of two of the most experimentally amenable apicomplexan species â human parasites Plasmodium falciparum and Toxoplasma gondii. As a foundation for the studies included in this thesis I used standard as well as recently developed computational algorithms, existing experimental datasets and innovative context- specific assumptions. I produced an extensive survey of the modeling efforts previously applied for studying metabolism of P. falciparum and available large-scale experimental datasets in comparison with the similar efforts made in other species. Further, I curated an existing model of metabolism in Plasmodium falciparum with respect to an up-to-date primary literature on metabolism of the parasite and addressed several important assumptions implicitly made in this model. Using a state-of-the-art approach, I reconstructed de novo a comprehensive metabolic model of T. gondii, and performed an extensive computational analysis to explore its metabolic needs and capabilities. I identified and classified the minimal set of substrates the parasite utilizes for growth, along with the genes and pairs of genes that are essential for cellular functions such as growth and energy metabolism. Subsequently, several of the model-driven hypotheses were confirmed experimentally, while for validation of the majority of the computational predictions forthcoming high-throughput approaches shall be used. Every confirmed hypothesis expands the scope of our knowledge on peculiarities of metabolism in apicomplexan parasites and hence can serve as an input for the pipeline of developing novel medicines.

EPFL2015

Metabolic Needs and Capabilities of Toxoplasma gondii through Combined Computational and Experimental Analysis

Vassily Hatzimanikatis, Jens Nielsen, Rebecca Oppenheim, Dominique Soldati-Favre, Stepan Tymoshenko

Toxoplasma gondii is a human pathogen prevalent worldwide that poses a challenging and unmet need for novel treatment of toxoplasmosis. Using a semi-automated reconstruction algorithm, we reconstructed a genome-scale metabolic model, ToxoNet1. The reconstruction process and flux-balance analysis of the model offer a systematic overview of the metabolic capabilities of this parasite. Using ToxoNet1 we have identified significant gaps in the current knowledge of Toxoplasma metabolic pathways and have clarified its minimal nutritional requirements for replication. By probing the model via metabolic tasks, we have further defined sets of alternative precursors necessary for parasite growth. Within a human host cell environment, ToxoNet1 predicts a minimal set of 53 enzyme-coding genes and 76 reactions to be essential for parasite replication. Double-gene-essentiality analysis identified 20 pairs of genes for which simultaneous deletion is deleterious. To validate several predictions of ToxoNet1 we have performed experimental analyses of cytosolic acetyl-CoA biosynthesis. ATP-citrate lyase and acetyl-CoA synthase were localised and their corresponding genes disrupted, establishing that each of these enzymes is dispensable for the growth of T. gondii, however together they make a synthetic lethal pair.

Public Library Science2015

Reconstruction and systems analysis of metabolism in apicomplexan parasites Toxoplasma gondii and Plasmodium falciparum

Stepan Tymoshenko

EPFL2015