Toxin | EPFL Graph Search

A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919) and is derived from the word "toxic". Toxins can be small molecules, peptides, or proteins that are capable of causing disease on contact with or absorption by body tissues interacting with biological macromolecules such as enzymes or cellular receptors. They vary greatly in their toxicity, ranging from usually minor (such as a bee sting) to potentially fatal even at extremely low doses (such as botulinum toxin). Terminology Toxins are often distinguished from other chemical agents strictly based on their biological origin. Less strict understandings embrace naturally occurring non-organic toxins, such as arsenic. Other understandings embrace synthetic analogs of naturally occurring organic poisons as toxins, and may or may not embrace natura

The double-edged toxins

Mario Gonzalo Garcia Arraez

Many insect species are associated with endosymbiotic bacteria which have the particularity of living within host tissues. Endosymbionts benefit from this stable and nutritious environment, while providing ecological advantages to their host, such as protection against parasites or thermal tolerance. Spiroplasma poulsonii is an endosymbiotic bacterium that infects natural populations of Drosophila melanogaster. Spiroplasma poulsonii lacks a cell wall, a fact that renders it invisible to the host immune system and allows it to thrive in the host hemolymph. It invades the female germline by co-opting the hostâs yolk transport and uptake machinery, which ensures its vertical transmission. Its efficient transmission is associated with a phenotype called male-killing, whereby infected male embryos die during their early development while infected females survive. The mechanisms that ensure the stability of Drosophila-Spiroplasma symbiosis are increasingly well understood, but the bacterial genes involved remain poorly known because of the intractability of Spiroplasma. This project aims at better characterizing the Drosophila-Spiroplasma interaction, with particular focus on the bacterial side. In the first part, I developed a method to cultivate Spiroplasma poulsonii in vitro by optimizing a commercially available medium. This culture method allowed comparing the transcriptome of in vitro grown versus host-grown Spiroplasma, enabling us to identify putative genes involved in the interaction with the host. Interestingly, inside its insect host, S. poulsonii up-regulates genes coding for toxins of the Ribosomal Inactivating Protein (RIP) family. RIPs were previously known for their role in host protection against macro-parasites, such as wasps and nematodes. Their up-regulation in unparasitized hosts compared to culture was thus peculiar, raising the question what effect these RIPs have on host biology. Thus, in the second part, I studied the function of S. poulsonii RIPs in the absence of parasites. I showed that two of them are constantly expressed within the host and provide evidence that these toxins shorten host life span and increase embryonic mortality. Interestingly, the expression of RIPs was more toxic to male embryos than females, suggesting that RIPs contribute to S. poulsonii-induced male-killing. Last, I studied the D. melanogaster response to RIPs, and how the host mitigates the deleterious effects of these toxins by up-regulating the cytosolic chaperone Heat-Shock-Protein 70B (HSP70B). This protein carries out essential functions in protein homeostasis under normal and stressful conditions such as folding, refolding, or increasing the half-life of proteins. Interestingly, up-regulation of Hsp70B in the presence of RIPs results in an increased lifespan and in a better tolerance to heat stress, which may be ecologically advantageous. Altogether, this work illustrates how Spiroplasma-derived RIP toxins can differentially affect Drosophila depending on the ecological context, ranging from beneficial upon parasite infection or heat shock to detrimental in the absence of such environmental pressures.

EPFL2018

Gas Sampling Using Convection and Humidity Stabilization to Improve Point Gas Sensor Responses

Emily Ann Hammes

Many diseases including sick building syndrome, respiratory problems and cancers can be caused by exposure to high concentrations of toxins commonly used in modern building materials, paints, glues and furniture. To minimize exposure to these toxins, it is important to have air exchange with the outside environment. However, this is usually not energy efficient because the air must be heated or cooled. The purpose of the Intasense project was to resolve this problem by creating an air quality monitor which could determine the current quality of air within the building. This information would then be used to control the ventilation system within an energy efficient building. The purpose of this Ph.D. thesis was both to build a system which could be used to test and calibrate sensors used in the air quality monitor as well as to build its final fluidic platform. During this thesis, three fluidic platforms which include a humidity buffering system were designed, tested and constructed. The first platform was used to test an electrochemical sensor or metal oxide sensor in the laboratory. The second and third platforms held three electrochemical or metal oxide sensors, respectively. They are able to deliver equal quantities of gas to the sensors simultaneously. To date, the multisensor metal oxide platform has been used to create two versions of the Intasense Demonstrator and used to calibrate novel and commercial gas sensors. In both of these applications simultaneous delivery of equal quantities of the sample gas are required for optimal gas sensor signal processing: equal quantities are required so that the amount of analyte in contact with each sensor is the same and simultaneous delivery allows all three sensors to respond concurrently. This was achieved by creating a computational model of gas flow through the system, conducting a parameter sweep and then selecting the optimal set. To confirm that the model and machine error were not significant, a Latin square design was used to test the platform. This test showed that gas delivery to each channel was equal within statistical boundaries. Another major challenge was buffering humidity fluctuations without loss of analyte gas. This was necessary because metal oxide gas sensors are also sensitive to humidity fluctuations. To prevent a false positive caused by a rapid humidity increase, a reversible adsorbent was placed upstream of the gas sensors. However, there was concern that the adsorbent may remove analyte gasses. To optimize the tradeoff between humidity buffering and loss or delay of analyte signal, a computational model of adsorption and desorption of gasses within the filtration system was developed. It was experimentally tested using benzene, carbon monoxide, formaldehyde and nitrogen dioxide. To date ten platforms have been delivered to laboratories throughout Europe. Three are being used to test and calibrate gas sensors. The rest have been used to create demonstrators of the Intasense Air Quality Monitor.

EPFL2016

About lipids and toxins

Françoise Gisou van der Goot Grunberg

Many mono or multicellular organisms secrete soluble proteins, referred to as protein toxins, which alter the behavior of foreign, or target cells, possibly leading to their death. These toxins affect either the cell membrane by forming pores or modifying lipids, or some intracellular target. To reach this target, they must cross one of the cellular membranes, generally that of an intracellular organelle. As described in this minireview, lipids play crucial roles in the intoxication process of most if not all toxins, by allowing/promoting binding, endocytosis, trafficking and/or translocation into the cytoplasm

2006