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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.