Understanding the role of lipoxidation in tumorigenic signalling

Phosphatase and tensin homolog (PTEN) is a key redox-sensitive tumour suppressor that antagonizes the PI3K-Akt cell signalling pathway and limits cell proliferation.  Dysregulation of this pathway plays a role in breast cancers and in metabolic diseases. There is a strong link between inflammation, which causes oxidative stress, and cancer progression, but the mechanisms involved are not well understood. PTEN also affects other pathways through its protein phosphatase activity. This project will build on work at Aston using liquid chromatography tandem mass spectrometry to show that PTEN is covalently modified by reactive lipid oxidation products (a process called lipoxidation) produced during oxidative stress, which affects PTEN activity, localization and Akt activation.  The aim of the project is to understand which cellular mechanisms contribute to deleterious cellular outcomes and identify the specific downstream signalling processes that are differentially affected in tumorigenic and non-tumorigenic breast epithelial cells.

Objectives:

1. To determine the effect of oxidized lipid products on Akt, mTORC and GSK3 activation in tumorigenic (MCF-7) and non-tumorigenic (MCF-10A) cells using western blotting. qRT-PCR will be used to monitor PTEN and AKT transcript levels.
2. To determine the effect of PTEN signalling on mitochondrial bioenergetics, mitochondrial dynamics and mitophagy in MCF-7 and MCF-10A using real-time oxygen consumption measurements and western blotting.
3. To identify specific modifications of PTEN and its protein-protein interactions in MCF-7 and MCF-10A cells under inflammatory or stress conditions, using LC-MSMS approaches.
4. To correlate changes in PTEN interactions and signalling with cellular outcomes (e.g. cellular proliferation, migration and invasion). 

Together, this will provide detailed information on the contribution of redox stress and lipid oxidation to altered cell signalling and metabolism in tumour cells. 

The successful applicant should hold or expect to achieve:

A Bachelors degree in a relevant subject with an award of First Class or Upper Second Class (minimum 60% overall weighting), and a Masters degree in a relevant subject with a minimum Merit award or higher.

Or

A Bachelors degree in a relevant subject with an award of First Class, plus substantial and relevant research experience

Desirable / Essential Skills or Experience 

Candidates with an interest of cancer cell biology, signalling or biochemistry are particularly encouraged to apply

This project covers all tuition fees and includes an annual stipend of £21,805. The studentship also includes consumable costs, and one return economy airfare and visa costs to the value of up to £2,500. 

Further information can be found here: Financial Requirements | Aston University.
 

This position will be based on the Aston Campus in Birmingham, UK. The successful candidate will need to be located within a reasonable distance of the campus, and will be expected to visit in person regularly. 

Submitting an application

We can only consider applications that are complete and have all supporting documents. Applications that do not provide all the relevant documents will be automatically rejected. Your application must include: 

1. English language copies of the transcripts and certificates for all your higher education degrees, including any Bachelor's degrees.
    
2. A Research Statement detailing your understanding of the research area, how you would approach the project, and a brief review of relevant literature. Be sure to use the title of the research project you are applying for. There is no set format or word count. 
    
3. A personal statement which outlines any further information which you think is relevant to your application, such as your personal suitability for research, career aspirations, possible future research interests, and further description of relevant employment experience. 
    
4. Two academic referees who can discuss your suitability for independent research. References must be on headed paper, signed and dated no more than 2 years old. At least one reference should be from your most recent University. You can submit your references at a later date if necessary. 
    
5. Evidence that you meet the English Language requirements. If you do not currently meet the language requirements, you can submit this at a later stage. 
    
6. A copy of your passport. Where relevant, include evidence of settled or pre-settled status.

Interviews

Interviews will be conducted online via Microsoft Teams. If you are shortlisted, you will be contacted directly with details of the interview.  

Studying a PhD is great route into academia and industries that are centred on research and innovation. Areas with a demand for very high level and specialised research skills often demand PhDs.

In addition to this specialist knowledge, PhD education will help you to develop a set of valuable transferrable skills. The very nature of studying an intensive research degree will enable you to become a team player, develop problem-solving skills, analytical thinking, and advanced presentation and communication skills.

The variety of PhD project topics at Aston means that the destinations of our graduates vary substantially. Some choose to continue into academia, at either Aston or other leading institutions, while others go onto use their newly acquired skills in a range of research, healthcare, industry or charitable fields. When selecting your chosen PhD path at Aston, your supervisor will be able to provide you with relevant career opportunities that could be available to you in your specialist area.