About the Project
Interested individuals must follow Steps 1, 2 and 3 at this link on how to apply
http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply
Trypanosomatid parasites account for a number of neglected tropical and livestock diseases and present a huge health and economic burden in many developing countries. These organisms have a distinctive, essential RNA editing pathway, known as uridine deletion/insertion editing. During editing, mitochondrial mRNAs are recoded using small guide RNAs (gRNAs) that anneal to mRNA sequences and direct cleavage; insertion and/or deletion of U bases; and re-ligation at specific sites. Core enzymatic activities associated with editing are found in 20S editosome complexes, which coordinate with other mRNA processing enzymes to deliver edited, mature mRNAs to the ribosome. Key questions that we wish to address are how editosomes use RNase III enzymatic activity, usually associated with double stranded RNA cleavage, to cut only the mRNA strand and how mRNA strands at edited sites are subsequently ligated together.
This is an interdisciplinary project between and the Cook and Schnaufer labs. The student will undertake biophysical, biochemical and structural studies on enzymes involved in trypanosomal RNA editing and use information from these studies to generate functional hypotheses that can be tested in the organism. The main methodologies used will be protein purification and biochemical characterization; RNA biochemistry; X-ray crystallography; biophysical characterization e.g. surface plasmon resonance, isothermal titration calorimetry; trypanosomatid culture and characterisation
This project will be joint supervised by Atlanta Cook and Achim Schnaufer
http://www.wcb.ed.ac.uk/research/cook
http://schnauferlab.bio.ed.ac.uk/
http://cook.bio.ed.ac.uk/
References
Panigrahi, A.K., Ernst, N.L., Domingo, G.J., Fleck, M., Salavati, R. and Stuart, K.D. (2006) Compositionally and functionally distinct editosomes in Trypanosoma brucei. RNA, 12, 1038-1049.
Schnaufer, A., Wu, M., Park, Y.J., Nakai, T., Deng, J., Proff, R., Hol, W.G. and Stuart, K.D. (2010) A protein-protein interaction map of trypanosome ~20S editosomes. J Biol Chem, 285, 5282-5295.
Carnes, J., Trotter, J.R., Ernst, N.L., Steinberg, A. and Stuart, K. (2005) An essential RNase III insertion editing endonuclease in Trypanosoma brucei. Proc Natl Acad Sci U S A, 102, 16614-16619.
Trotter, J.R., Ernst, N.L., Carnes, J., Panicucci, B. and Stuart, K. (2005) A deletion site editing endonuclease in Trypanosoma brucei. Mol Cell, 20, 403-412.
Kang, X., Gao, G., Rogers, K., Falick, A.M., Zhou, S. and Simpson, L. (2006) Reconstitution of full-round uridine-deletion RNA editing with three recombinant proteins. Proc Natl Acad Sci U S A, 103, 13944-13949.