Key facts
- Type of research degree
- PhD
- Application deadline
- Ongoing deadline
- Country eligibility
- International (open to all nationalities, including the UK)
- Funding
- Non-funded
- Supervisors
- Dr Eric Hewitt
- Additional supervisors
- Professor S E Radford; Dr P Actis
- Schools
- School of Molecular and Cellular Biology
Intraneuronal inclusions known as Lewy bodies are a hallmark of Parkinson’s disease. Amyloid fibrils formed by the misfolding of alpha-synuclein are the principal component of Lewy Bodies. However, the role of these fibrils and their oligomeric assembly intermediates in neuronal death is poorly understood. This is because alpha-synuclein misfolds into amyloid fibrils in the cytoplasm, whereas experimental studies have typically involved adding fibrils and oligomers to the cell culture medium. Although this enables biophysical characterisation of the fibrils and oligomers before addition to the cells, their access to the cytoplasm is limited. <br /> <br /> This project will use a single molecule nanoinjection platform to deliver alpha-synuclein fibrils and oligomers into the cytoplasm of neurons. Nanoinjection uses quartz needles (≤50nm pore diameter), known as nanopipettes, to deliver molecules into cells. The nanopipettes incorporate electrodes and application of a voltage drives the transport of molecules through the pore. When a protein passes through the nanopipette’s pore there is a corresponding disruption in the ion flow, thus the number of proteins delivered into a cell can be quantified. Thus this project will not only determine whether α-synuclein fibrils or oligomers are toxic in the cytoplasm, but for the first time it will quantify the number of each required to kill a neuron.
<p>Fibrils and oligomers will be made from recombinant α-synuclein, charactersied using an array of biophysical techniques, and nanoinjected into neuronal cell lines and primary neurons. To inject cells the nanopipette will be used as a probe for a scanning ion conductance microscope, which will generate a topographical map of the target cell. This information is used to insert the nanopipette into the cell at a pre-defined depth and location. Application of a voltage will drive the delivery of the fibrils or oligomers into the cell. By monitoring the corresponding disruptions in ion flow, a defined number of oligomers or fibrils will be delivered. The cellular effects of the nanoinjected fibrils and oligomers on cell stress and viability will then be analysed using microscopy-based assays. </p> <p>This PhD will be a collaborative project in the Astbury Centre for Structural Biology and Bragg Centre at the University of Leeds between the research groups of Dr Eric Hewitt, Dr Paolo Actis and Professor Sheena Radford FRS OBE. The project will provide training in interdisciplinary science, with the PhD student developing expertise at the interface of the nanotechnology, molecular cell biology and structural biology. </p>
<p>To apply for this project opportunity applicants should complete an <a href="https://biologicalsciences.leeds.ac.uk/research-degrees/doc/how-to-apply">online application form</a> and attach the following documentation to support their application. </p> <ul> <li>a full academic CV</li> <li>degree certificate and transcripts of marks</li> <li>Evidence that you meet the University's minimum English language requirements (if applicable)</li> </ul> <p>To help us identify that you are applying for this project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Biological Sciences as your programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> </ul> <p>If English is not your first language, you must provide evidence that you meet the University's minimum English language requirements (below).</p> <p><em>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.</em></p>
Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.
The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.
<p>This project is open to applicants who have the funding to support their own studies or who have a sponsor who will cover these costs. <br /> </p>
<p>For information about the application process please contact the Faculty Admissions Team:</p> <p>e: <a href="mailto:fbsgrad@leeds.ac.uk">fbsgrad@leeds.ac.uk</a></p>