Biophysics of Cyst Formation in the Human Pathogen Entamoeba Histolytica -Physics and Astronomy, Biosciences - EPSRC DTP funded PhD Studentship.

About the award

This project is one of a number funded by the Engineering and Physical Sciences Research Council (EPSRC) Doctoral Training Partnership to commence in September 2018. This project is in direct competition with others for funding; the projects which receive the best applicants will be awarded the funding.

The studentships will provide funding for a stipend which is currently £14,553 per annum for 2017-2018. It will provide research costs and UK/EU tuition fees at Research Council UK rates for 42 months (3.5 years) for full-time students, pro rata for part-time students.

Please note that of the total number of projects within the competition, up to 15 studentships will be filled.

Location
Streatham Campus, Exerer

Project Description
Entamoeba histolytica is an intestinal parasite that infects 50-100 million people worldwide and causes up to 55,000 deaths annually. The transmissive form of E. histolytica is the cyst, with a single infected individual passing up to 45 million cysts per day, making cyst production an attractive target for infection control. Although the molecular biology of cyst formation is relatively well understood, the biophysics of this process is totally unexplored. This proposal will investigate fundamental questions of the biophysics of encystation, i.e. how the interactions between cell-secreted components and the cell membrane lead to the formation of a rigid cyst wall. The project will focus on the following three areas:

1. Membrane electrical properties. We will aim to understand the changes in the plasma membrane organisation in the course of cyst formation. To quantify these, we will measure the membrane electrical properties (membrane dipole and surface potentials) during cyst formation which will clarify the role of the Entamoeba plasma membrane in cyst formation and the changes in molecular structure (e.g. lipid packing) and mesoscopic membrane organisation (e.g. clustering and formation of microdomains) during this process. We will use a fluorescence-based methods implemented in our laboratory for measuring membrane electrostatic potentials [1].

2. Langmuir trough measurements. This technique allows the study of the interactions between components secreted by the cell and a monolayer of lipids spread at an air-water interface (a model for the plasma membrane). We will investigate the role of each individual component (lectin, chitin-binding proteins, chitin, chitosan) in determining and regulating the organisation and mechanical properties of the emerging rigid wall.

3. Model lipid bilayers. Lipid bilayers offer a more realistic model for the plasma membrane. We have developed techniques based on the analysis of thermal membrane fluctuations of erythrocytes to assess the effects of the protein-membrane interactions on the membrane curvature and mechanical properties [2-4]. This offers the opportunity to use a single red blood cell as a reporter for interactions with various species and precise quantification of changes in membrane mechanical properties such as bending rigidity, shear elasticity and membrane tension. These experiments will reveal how chitin, chitosan, lectin and chitin-binding proteins interact together and with the plasma membrane to form the rigid wall of the cyst.

This project is an important step in building a biophysical model of infectious cyst formation of the intestinal pathogen Entamoeba which causes amoebiasis. A fundamental understanding of this process will inform future intervention and prevention strategies against this disease.

Entry Requirements
You should have or expect to achieve at least a 2:1 Honours degree, or equivalent, in a natural science, preferably biology or physics. Experience in biophysical research is desirable.

If English is not your first language you will need to meet the English language requirements and provide proof of proficiency.

The majority of the studentships are available for applicants who are ordinarily resident in the UK and are classed as UK/EU for tuition fee purposes. If you have not resided in the UK for at least 3 years prior to the start of the studentship, you are not eligible for a maintenance allowance so you would need an alternative source of funding for living costs. To be eligible for fees-only funding you must be ordinarily resident in a member state of the EU.

Applicants who are classed as International for tuition fee purposes are NOT eligible for funding. International students interested in studying at the University of Exeter should search our funding database for alternative options.