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Transcript
Important projects currently running in CIIE Micro RNAs in infection (Amy Buck, Rick Maizels, Francisca Mutapi) Very small bits of genetic information are packaged into little vesicles circulating in our bodies. We’ve found that parasites make these vesicles to move information to the host, as a mechanism of improving their environment for survival. These little bits of information can also be detected in body fluids and can tell you if you are infected. Minicircle inheritance in trypanosomes: experimental-mathematical (Nick Savill and Achim Schnaufer) This project studies the mitochondrial DNA of the sleeping sickness parasite Trypanosoma brucei. When a trypanosome divides it has to accomplish faithful duplication of its kinetoplast (thousands of circular DNAs that form a gigantic network that has been likened to medieval chainmail) so that each daughter cell inherits the complete set of genes that is encoded in this genome. We want to understand how many genes exactly are encoded in the kinetoplast, and how the parasite ensures faithful kinetoplast duplication and segregation. For this we use a combination of cutting edge DNA sequencing technology, mathematical modelling, and lots of computer power. Parasite-parasite communication in African trypanosomes (Keith Matthews, Liam Morrison, Jacqui Matthews) African trypanosomes are parasites, spread between mammals by tsetse flies. They are responsible for epidemics of sleeping sickness, the second biggest killer behind HIV in parts of Africa, and some related diseases in cattle. Unless treated, sleeping sickness is fatal. Trypanosomes survive free in the bloodstream of mammalian hosts. Here they reproduce as slender forms. However, as parasite density increases they transform to so-called stumpy forms. Stumpy forms do not divide and are preadapted for survival and transformation when taken up in the bloodmeal of a tsetse fly. Stumpy forms are crucial in the transmission of trypanosomes. Once stumpy forms enter the tsetse fly they transform again into procyclic forms. We are trying to understand how the parasite controls its population density and its growth in infected mammals. We also investigate the mechanisms behind parasites' responses to environmental signals after being ingested by the tsetse fly. Clinical-experimental analysis of malaria samples from human infections (Alex Rowe/Phil Spence) In collaboration with the Jenner Institute, Oxford, we are experimentally infecting human volunteers with Plasmodium falciparum, the most deadly human malaria parasite. In the first week of infection (before volunteers are drug-cured) we are sampling the parasites and the host response, so that we can piece together the earliest events in malaria. This will tell us how parasites trigger & evade host immunity, and also identify early host decisions that dictate whether an individual lives or dies. Populations (Amy Pedersen and Mark Woolhouse) This theme is about how populations of pathogens (viruses, bacteria parasites) spread through populations of hosts (humans, cattle, wild mice). It reveals rich and often counterintuitive dynamics and provides information vital to the design of effective interventions to prevent the spread of infectious diseases. Chronobiology of infection (Sam Rund and Sarah Reece) Organisms experience a world that is constantly changing in a 24 hour manner. The rising and the setting of the sun leads to rhythms in ambient light, temperature, humidity, ultraviolet light, etc. In response, organisms have evolved 24 hour circadian rhythms in sleep:wake cycles, immune system function, and metabolism. These rhythms are driven both by responding to light, but also to an molecular clock that is able to keep time in the absence of light. It is this internal clock that is responsible, for example, for the phenomenon of 'Jet - lag.' We are interested in how circadian rhythms in host organisms, pathogens, and disease vectors (such as mosquitoes) interact to effect infection and disease transmission. Ebola virus outbreak (Andy Rambaut, Gydis Dudas) Time leaves clues in the genomes of all organisms in the form of mutations. Looking at these imprints we can find out how distantly species or even individuals are related and how populations have changed in size through time. Analysis of the genomes sequences of Ebola virus from Sierra Leone and Guinea indicates that the virus has probably only jumped into humans there once after having been introduced into West Africa from Central Africa some time in the last decade, most likely by bats. Immunity and ageing in wild mammals (Rebecca Watson, Rose Zamoyska, Tom McNeilly and Dan Nussey) The immune system is very effective at protecting us from harmful infectious organisms (pathogens), however, we have little understanding of how natural selection impacts on immune condition. Humans, experimental and domestic animals live in controlled environments so are rarely exposed to selection by pathogens. Our study population of wild Soay sheep living on the island of St.Kilda, Scotland, is unmanaged and allows us to study the interaction between infectious organisms and the immune system, and to monitor their combined impacts on the health, longevity and reproduction of individuals and of the population.