Human and livestock diseases caused by trypanosomatid parasites threaten health and livelihood of millions of people in Africa, South America and Asia. Many of the affected populations live in remote rural areas with limited access to adequate health service. The aim of this project is to increase our understanding of the genomic structure and function of trypanosome mitochondrial DNA (the kinetoplast) in the hope of aiding drug discovery but also to understand fundamental aspects of mitochondrial bioenergetics, genetics and genome structure. The kinetoplast is remarkable and completely different from human mitochondrial DNA. It is made up of thousands of interlocked DNA rings like chainmail armour. These rings, called minicircles, encode guide-RNAs that direct post-transcriptional editing of mRNA. In some genes, almost half the genetic information is edited into the mRNA. Our groups (combining molecular biologists, mathematical biologists and biophysicists) are interested in determining the complexity of the kinetoplast structure and genetic content and how these relate to each other. Comparison between different parasite species will reveal common and lineage-specific characteristics. To achieve this goal, we use a combination of mathematical modelling (e.g. Bayesian statistical and computational modelling), bioinformatics, biochemistry, next-generation sequencing, structural determination (e.g. atomic force microscopy, AFM) and genetic manipulation of parasites.
The student will obtain cross disciplinary training in cutting edge molecular and cellular biology, mathematical and computational biology, and biophysics. They will learn how to construct bioinformatic pipelines for genome assembly, how to develop mathematical models describing the evolution of kinetoplast structure and function, and how to use AFM to investigate kinetoplast structure.
http://schnauferlab.bio.ed.ac.uk/
http://homepages.ed.ac.uk/nsavill/
www2.ph.ed.ac.uk/~dmichiel/
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