About the Project
The mitochondrial DNA of trypanosome parasites (kinetoplast or kDNA) is one of the most topologically complex genomes in nature1–3. It forms a two-dimensional Olympic ring-like network composed of thousands of concatenated circular DNA molecules. These interlocked structures exhibit unusual biophysical properties, including ultra-softness and non-linear elasticity, with potential to challenge current material paradigms. At the same time, kDNA is a validated target for anti-trypanosomatid drugs, although their precise mode-of-action remains unclear.
This PhD project will investigate how kDNA is organised and replicated, and how the self-assembly of this extraordinary structure is perturbed by anti-trypanosomatid drugs. Combining single-molecule imaging (atomic force microscopy, AFM), dynamic differential microscopy (DDM), DNA labelling, and computational modelling will uncover the rules that govern kDNA assembly and the molecular factors that make it vulnerable to certain drugs. Ultimately, the project will enable future large-scale biosynthesis of Olympic gels made of DNA molecules, inspired by the biogenesis and replication of the kDNA.
Experimentally, the student will synchronise trypanosomes at different stages of the kDNA replication cycle, then measure kDNA structure using AFM, fluorescence microscopy, and DDM3,4. Next, they will develop a computational model to explain the observed structures using a minimal set of molecular ingredients, such as topoisomerase activity, DNA polymerase and DNA-condensing proteins. These predictions will be tested by perturbing the system in vivo genetically and with anti-kDNA drugs, and observing changes in kDNA network. These insights will inform the design of in vitro kDNA synthesis using plasmids and recombinant topoisomerases. Comparison of the “synthetic” kDNA structures against the native kDNAs will further guide the refinement of our design through iteration of the designbuild-test-learn cycle.
A partnership with Dyneval strengthens the project by bringing in expertise in DDM-based analysis and enabling quantitative characterisation of both kDNA structure and parasite motility. This will give the student access to additional methodological know-how and a translational bridge between fundamental parasite biophysics and advanced imaging analysis. It also fits the project’s interdisciplinary design: DDM can be used to turn complex image data into quantifiable parameters to measure the efficacy of kDNAtargeting drugs.
Overall, this project addresses a major gap in understanding of how cells manage highly entangled genomes, a problem that is relevant beyond trypanosomes. It will also inform the scalable design of interlocked DNA materials and clarify the mechanisms of existing anti-trypanosomal drugs, while offering interdisciplinary training across biology, physics, and computation on a topic that is both fundamentally interesting and industrially-relevant. Applicants need to be able to work at the intersection of molecular biology and computational modelling, a strong background in both biology and maths is essential.
For more information on the project, eligibility and how to apply for the School's PhD programme, please click on the 'Visit Institution Website' link.
Please download and complete the mandatory documents from the EastBio “how to apply” website, before proceeding with your application.
Applicants should apply to the PhD in Biological Sciences with Internship programme via the University of Edinburgh’s admissions portal (Euclid) with a start date of 01 October 2027.
Important: Before applying, please send your referees the EastBio reference form to ensure reference letters are submitted using the correct format.
When completing the Euclid application, applicants should include:
- the project title
- the proposed research supervisor(s)
- anticipated funding source (i.e. EastBio/ Edinburgh Doctoral College Award)
- the completed EastBio application form, uploaded to the Research Proposal Section
- referee details or completed reference letters using the template EastBio reference form. Please note: If you submit only the referee details, they will automatically receive a link to upload their reference letter. However, the submitted letter must be using the template form, so please share this with them in advance.
The closing date for applications to be submitted to Euclid is midday on Monday 16 November 2026.
Reference letters will be accepted up to 2 weeks after the closing date.
Submitted applications will remain under consideration during the shortlisting process until 22 February 2027, when successful candidates will be invited to interview. If any information is missing from your application, we will contact you through Euclid to request this. Please check your emails and the Euclid portal regularly.
Please be aware The University reserves the right, in its sole discretion, to amend or withdraw any of the advertised scholarships, without further notice.
Funding Notes
This 4 year PhD project is fully funded. Applicants will be considered for either an EastBio BBSRC Doctoral Landscape Award or the University of Edinburgh Doctoral College Award. Successful applicants will join the EastBio cohort as an EastBio-funded or associate-funded student. Those joining will undertake a mandatory training programme which includes a 3-month placement. This is open to students worldwide has financial support with a monthly stipend at the UKRI standard rate, funding towards project costs, and tuition fee cover. For further guidance; EastBio website; no separate application is required for consideration of the University of Edinburgh Doctoral College Award.
References
- Jensen, R. E. & Englund, P. T. Network News: The Replication of Kinetoplast DNA. Annual Review of Microbiology 66, 473–491 (2012). doi: 10.1146/annurev-micro-[contact details available in the full listing]
- Cooper, S. et al. Assembly and annotation of the mitochondrial minicircle genome of a differentiation-competent strain of Trypanosoma brucei. Nucleic Acids Research 47, 11304–[contact details available in the full listing]). doi: 10.1093/nar/gkz928
- Ramakrishnan, S. et al. Single-Molecule Morphology of Topologically Digested Olympic Networks. PRX Life 2, [contact details available in the full listing]). doi: 0.1103/PRXLife.2.013009
- He, P., Katan, A. J., Tubiana, L., Dekker, C. & Michieletto, D. Single-Molecule Structure and Topology of Kinetoplast DNA Networks. Phys. Rev. X 13, [contact details available in the full listing]). doi: 10.1103/PhysRevX.[contact details available in the full listing]
Project supervisors
Professor Achim Schnaufer
Career overview
Achim Schnaufer began studies as a Diploma student at the University of Giessen from 1991 to 1992. They then pursued a PhD studentship as a Research Assistant at the University of Bern from 1993 to 1997. Following this, Schnaufer worked at the Seattle Biomedical Research Institute (SBRI) in various roles, including Senior Research Fellow from 1998 to 2002, Research Associate from 2002 to 2003, Associate Scientist from 2003 to 2006, and Senior Scientist from 2007 to 2008. In 2008, Schnaufer joined the University of Edinburgh as an MRC Research Fellow, later becoming an MRC Senior Research Fellow and Reader in Parasite and Mitochondrial Biology from 2014 to 2018. Since 2018, Schnaufer has held the position of MRC Senior Research Fellow and Professor in Parasite and Mitochondrial Biology at the University of Edinburgh.
Research interests
Achim Schnaufer's research focuses on mitochondrial biogenesis, metabolism, and RNA processing in trypanosomatid protozoa, which are significant parasites affecting humans and livestock. The research is concentrated on two main areas: the role of mitochondria in the bloodstream stage of trypanosomes, particularly the adaptations that allow dyskinetoplastic trypanosomes to survive without their mitochondrial genome, and the evaluation of the trypanosome RNA editing complex as a potential drug target, with a specific interest in RNA editing ligase 1 (REL1) and its three-dimensional structure.
