About the Project
Protozoans cause significant infection worldwide, with the apicomplexan parasites Plasmodium spp., Toxoplasma and Cryptosporidium being respective etiologic agents of malaria, toxoplasmosis and cryptosporidiosis. Despite Toxoplasma being the most successful parasite on the planet, infecting around 30% of people worldwide, astonishingly little is known about the basic biology of this pathogen.
Invasion of host cells by apicomplexan parasites such as Toxoplasma initiates the host-pathogen interaction, and is accompanied by signalling events occurring within the parasite and host. Hydrogen peroxide (H2O2) is an organic small molecule present in cells that is gaining appreciation as an important signaling molecule. Toxoplasma parasites encounter exogenous H2O2 during development within a host cell, and when they exit that cell and are visible to host immune system. Although there is an appreciation that Toxoplasma experiences H2O2 signals, mechanisms for how they are detected and how the parasite responds is not known. Sparse data for ROS as signaling molecules reflects the difficulty in detecting these small molecules, and the lack of tools with which to study them. Excitingly, novel chemical proteomic approaches are now enabling functional description of ROS signals in cells.
In this project you will establish and apply new chemical proteomic platforms to delineate redox signaling in the obligate intracellular pathogen, Toxoplasma gondii. These will include small-molecule conditional proteomic approaches, and a gene-fusion technology based on the recently published APEX system. These proteomic platforms will be partnered with modern CRISPR-based genome editing and cell-based phenotyping to validate the mass-spectrometry findings and molecularly map H2O2 signaling in this pathogen.
Ultimately, this project aims to help us understand the biological relationship between host-cell invasion and H2O2, and shed light on how this pathogen is able to survive inside the body of a host. The technologies established will also have significantly broader impacts, enabling the study of these endogenous reactive small molecules in diverse biological systems.
The project would ideally suit an outstanding chemistry or biochemistry graduate with some existing research experience in proteomics, synthetic, bioorganic and/or protein chemistry, and a strong interest in developing and applying novel chemical tools to advance biology. An interest in microbiology and host-pathogen interactions would also be desirable. The successful candidate will receive training in all relevant aspects of chemical synthesis, protein chemistry, cell biology, Toxoplasma parasite culture, microscopy, and proteomics.
How to apply
Initial applications should include a full CV, names, addresses and contact details of two academic referees, a personal statement (500 words max) and a covering letter.
Completed applications should be submitted to the DTP Team via email ([Email Address Removed]) by 5pm on the 10th February 2017.
Please note only shortlisted applicants will be contacted by the project supervisors.
Informal enquiries are welcomed and should be sent to Dr Matthew Child, [Email Address Removed].
Funding Notes
Applicants are expected to hold, or to be awarded a first class or a good upper second class BSc Degree, or an equivalent qualification, by October 2017.
The studentships are offered on a 1+3 basis (1 Year of Masters study followed by 3 years of PhD Research). In every case, the Masters Course will commence in October 2017 followed by the commencement of the PhD in October 2018. Only UK and EU students who meet the UK residency requirements are eligible to apply (minimum of three years of continuous residency in the UK immediately prior to the start of the PhD). Non-EU nationals are not eligible.
The studentships cover: (i) an annual tax-free stipend at the standard Research Council rate, (ii) contribution towards research costs, and (iii) tuition fees at the UK/EU rate.
Continue with Facebook
