Bacillus anthracis is the spore-forming bacteria which causes Anthrax. It persists in the environment as inert spores which are ingested/inhaled by susceptible grazing animals. Germination of spores inside the host results in the production of two major plasmid borne virulence factors, an antiphagocytic capsule and a tripartite toxin composed of three proteins called protective antigen (PA), lethal factor (LF) and oedema factor (EF) which combine together to inactivate host immune cells allowing the replication of the pathogen to proceed unchecked. Current treatment options include antibiotics and vaccines which confer protection by stimulating the production of antibodies which inhibit the binding of PA to host cells. Following the death of a susceptible animal the bacteria converts back into its spore form and is released into the soil as the animal decays to await its next encounter with a susceptible host which may not be for many decades if at all.
It is thought that the spread of the spores through soil is facilitated by periods of local flooding, the spores float in certain types of water logged soil and as a consequence are transported to the surface and along water courses were they are more likely to encounter a susceptible grazing animal. A lack of understanding of the ecology of the disease coupled with ineffective veterinary services and unsafe disposal of infected carcasses means that the reservoir of spores is constantly being refreshed in area were the disease is endemic. The situation is being made worse by global warming in that the melting of frozen ground is releasing trapped spores and facilitating their spread. Climate change is predicted to drive an increase in the incidence of anthrax in northern latitudes where outbreaks in the Russian arctic, the most recent being in 2016, due to the melting of the permafrost, have devastated indigenous caribou-herding communities and resulted in cases of human infection (Walsh et al., Sci Rep. 2018 Jun 18;8(1):9269).
In addition to releasing spores trapped in the ice, thawing of the soil coupled the increase hydration and soil specific factors are thought to create areas in which spores can actively replicate thus creating the potential for mutations to occur and for the exchange of mobile genetic elements such as plasmid encoding virulence factors to occur between strain of the B. cereus group of which B. anthracis is a member resulting in the emergence of new pathogen strains.
Using a multi-disciplinary approach the student will employ a combination of real-world data capture, GIS modelling, laboratory-based experimentation and interviews with farmers to understand the potential impact of climate change on the evolution and dissemination of anthrax in the Kars region of North East Turkey. The disease is an on-going problem in this area which is above 2000m and suffers from cold winters with extensive snowing and warm summers. Melting of the winter snows create conditions for the spread of the pathogen from contaminated areas to locations which support replication. Using GIS technology and records of anthrax cases they will create a model which combines information about local water course and soil conditions to identifying future at risk areas. They will also travel to Turkey to examine the bacterial genomes of B. anthracis isolates using the Minion portable nucleic acid sequencing system and bioinformatics analysis to identify strains with mutations in the genes encoding PA and LF.
Using attenuated strains which carries the genes for PA and LF, we will determine the environmental conditions under which mutations occur. We will express mutated forms of PA and LF as recombinant proteins and determine their ability to evade protective immune responses potentially indicating an increase in virulence. This work will be undertaken in part in Italy.
Finally, the student will create a questionnaire for farmers in anthrax endemic regions to capture information about the history of their land use, water courses, history of anthrax outbreaks and carcass disposal. The results of this questionnaire in conjunction with the GIS model will be used by our colleagues in Turkey to educate farmers and vets (stakeholders) on the risks of anthrax and the association with rainfall, soil type and carcass management.
As well as tuition fees and a maintenance grant, all students receive access to OneZoo training and additional courses offered by the University’s Doctoral Academy and become members of the University Doctoral Academy
How to apply:
You can apply online - consideration is automatic on applying for a PhD with an October 2023 start date.
Please use our online application service at: https://www.cardiff.ac.uk/study/postgraduate/research/programmes/programme/biosciences-phd-mphil-md
and specify in the funding section that you wish to be considered for UKRI OneZoo funding.
Please specify that you are applying for this particular project and name the supervisor.
If not successful in being shortlisted for this particular studentship you could be considered for other studentships within the OneZoo program, please see the full list here: https://peter-kille.github.io/OneZoo/projects_2023.html
Application deadline: 1st May 2023 with interviews (either in person or online) being held on or around end of May and decisions being made by June 2023 for a 1st Oct 2023 start.
You must also by 1 May 2023 send the following to [Email Address Removed] (title of the email must include the name of the host institution to which you are applying, and the surname of the principal supervisor) e.g. "Cardiff_Baillie"
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