Development and assessment of genetic tools for Theileria apicomplexan transfection
Supervisors: Professor Dirk Werling, Dr Shan Goh and Dr Liam Good (Director, Tecrea)
Department: Pathology and Pathogen Biology
Theileria parva and T. annulata are intracellular protozoan pathogens, which cause disease in cattle. These pathogens have particular veterinary importance as there are limited treatment options, and they represent a significant economic burden in affected countries. Recent genomic data have accelerated efforts to identify T. parva and T. annulata antigens as vaccine targets. Many hypothetical antigens identified thus far have unknown function due to difficulties in transfection, and hence genetic manipulation, of the parasites. Transfection of other intracellular parasites, namely Plasmodium falciparum and Leishmania major were recently made possible using new methods. For example the use of cationic cell penetrating peptides attached to peptide nucleic acid (PNA) or morpholino oligomers (MO) enabled gene silencing in P. falciparum, and the use of a cationic polymer, polyhexamethylene biguanide (PHMB), facilitated delivery of oligodeoxynucleotides into L. major. We hypothesise that cationic PHMB and cell-penetrating peptides can facilitate entry of DNA, RNA, PNA or MO into intracellular Theileria organism at its most pathogenic stage, known as schizonts. This study aims to test the feasibility of these new delivery systems to create genetic tools for the study of T. parva and T. annulata schizont genes. These tools will fill a technology gap in Theileria research, particularly benefitting our internal programmes and network of collaborators. The technology will enable functional studies of hypothetical genes, and facilitate assessment of host-pathogen interactions.
The studentship will commence in October 2016.
Interviews for studentships - will be held on 16th March or in the w/c 21st March 2016 at the RVC’s Camden or Hawkshead Campuses
This is a three year fully funded studentship in partnership with Tecrea.
It is open to Home/EU applicants only. International students are welcome to apply but must be able to pay the difference between UK/EU and international tuition fees.
Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB). PLOS Neglected Tropical Diseases. 2015;9(10):e0004041.
Kolevzon N, Nasereddin A, Naik S, Yavin E, Dzikowski R. Use of peptide nucleic acids to manipulate gene expression in the malaria parasite Plasmodium falciparum. PLOS One. 2014;9(1):e86802.
Garg A, Wesolowski D, Alonso D, Deitsch KW, Ben Mamoun C, Altman S. Targeting protein translation, RNA splicing, and degradation by morpholino-based conjugates in Plasmodium falciparum. Proceedings of the National Academy of Sciences. 2015;112(38):11935-40