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EASTBIO Dynamics of mitochondrial genome complexity in trypanosomes


   School of Biological Sciences

  Dr A Schnaufer, Dr N Savill, Dr Frederik Van den Broeck  Thursday, December 16, 2021  Competition Funded PhD Project (Students Worldwide)

Edinburgh United Kingdom Biochemistry Bioinformatics Cell Biology Genetics Microbiology Molecular Biology Parasitology

About the Project

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 trypanosomal mitochondrial DNA (the kinetoplast) in the hope of aiding drug discovery but also to understand fundamental aspects of mitochondrial bioenergetics and genetics. The kinetoplast is quite remarkable and unlike human mitochondrial DNA. It is made up of thousands of interlocked DNA rings like chainmail armour. These rings, called minicircles, encode guide-RNAs that post-transcriptionally edit mRNA. In some genes, almost half the genetic information is edited into the mRNA. Our groups (one theoretical and another experimental) are interested in determining the complexity of the kinetoplast and how it evolves over time. We use a combination of mathematical modelling, bioinformatics, next-generation sequencing and experimentation to reveal and understand the wonderful complexity of the kinetoplast and its transcriptional and proteomic products – many, we suspect, have not yet been found.

The main goal of this project is to understand how such massive redundancy is maintained and to discover the function of the non-canonical gRNAs by combining sequence and transcriptomics data. The size and complexity of kDNA and its transcription products means that standard bioinformatics methods are incapable of elucidating its structure and function. This project will develop innovative Bayesian statistical and computational modelling methods to help achieve this.

The candidate will obtain training in cutting edge molecular biology, next generation sequencing. They will learn about modern bioinformatic tools available and how to construct bioinformatic pipelines to analyse genomic and transcriptomic sequences.

The student will also learn how to develop mathematical models describing the evolution of minicircle structure and function. They will learn how to write scientific computer code to simulate their mathematical models.

The School of Biological Sciences is committed to Equality & Diversity: https://www.ed.ac.uk/biology/equality-and-diversity

 How to Apply:

The “Institution Website” button will take you to our online Application Checklist. From here you can formally apply online. This checklist also provides a link to EASTBIO - how to apply web page. You must follow the Application Checklist and EASTBIO guidance carefully, in particular ensuring you complete all the EASTBIO requirements, and use /upload relevant EASTBIO forms to your online application.


Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership View Website
This opportunity is open to UK and International students and provides funding to cover stipend and UK level tuition fees. The fee difference will be covered by the University of Edinburgh for successful international applicants. UKRI eligibility guidance: Terms and Conditions: View Website International/EU: View Website

References

Savill and Higgs (1999). A theoretical study of random segregation of minicircles in trypanosomatids. Proceedings of the Royal Society B – Biological Sciences, 266:611–620. doi: 10.1098/rspb.1999.0680
Cooper et al. (2019). Assembly and annotation of the mitochondrial minicircle genome of a differentiation-competent strain of Trypanosoma brucei. Nucleic Acids Res 47(21):11304-11325. doi: 10.1093/nar/gkz928
Van den Broeck et al. (2020). Ecological divergence and hybridization of Neotropical Leishmania parasites. Proc Natl Acad Sci U S A 117(40):25159-25168. doi: 10.1073/pnas.1920136117
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