Self-funded PhD opportunities

Genetic-proteomic analyses of P2X7 receptors in health and disease.

  • Application end date: Applications accepted all year round
  • Funding Availability: Self-funded PhD students only
  • Department: School of Pharmacy and Biomedical Sciences
  • PhD Supervisor: Professor Darek Gorecki, and Dr Gianluca Tozzi

Project code: PHBM3771018

Project in detail

P2X7 is an ATP receptor with a number of physiological functions but also involved in acute and chronic diseases, e.g. inflammation, cancer, bone loss and psychiatric disorders. P2X7 is therefore an important therapeutic target. However, P2X7 trimeric subunit organization and its interacting partners (signalling and scaffolding proteins) can be highly diverse in various cells and pathologies. Moreover, cell-specific and sub-cellular localisation of P2X7 is still controversial. Understanding these multiple modes of action and cell -specific receptor functions is essential for developing targeted and effective treatments.

Given the importance of the P2X7 receptor in health and disease, our laboratory has created a unique P2X7 knock-in/knock-out mouse. It expresses endogenous levels of tagged P2X7 isoforms allowing immunoaffinity purification of the tagged P2RX7 followed by mass spectrometry to identify the associated proteins (the “genetic-proteomic”, Bienvenu et al, 2010). These tags also allow immunodetection of specific isoforms with anti-tag antibodies in situ.

Moreover, this mouse P2X7 gene is flanked by loxP sites allowing cell-specific and/or conditional knockouts by crossing this strain with specific Cre recombinase-expressing mice or by targeted expression of Cre recombinase.

This model takes functional analyses to a new level by defining the roles of P2X7 in any desired tissue or at any disease stage in vivo. These will be explored in this PhD project using molecular biology and proteomics methods to identify receptor assemblies and interacting proteins, confocal and advanced X-ray microscopy (http://www.port.ac.uk/school-of-engineering/zeiss-global-centre/) to unravel cellular and sub-cellular localisation of this receptor and functional analyses in specific cells and tissues (e.g. bone, brain) following cell-specific ablation by Cre recombinase.

Supervisor Profiles

Darek Gorecki

Gianluca Tozzi

Entry Requirements

Candidates must have a good honours degree or equivalent in a relevant subject or a master’s degree in an appropriate subject. Exceptionally, equivalent professional experience and/or qualifications will be considered. Please see the Key Facts section on your preferred research degree page for basic entry requirements.

Enquiries

Informal enquiries are welcome and can be made to Professor Darek Gorecki on 02392 843566 (darek.gorecki@port.ac.uk) or 02392 842514 (gianluca.tozzi@port.ac.uk).

Formal enquiries can be made to the faculty via the enquiry form on the subject specific pages.

The start date for this self-funded PhD will be October 2017 or February 2018.

How to apply

To apply, please submityour CV, a one-page letter of application, two references, copies of any relevant qualifications and evidence of IELTS if required.

All applications should use our standard online application form and follow the instructions given under the ‘Research Degrees’ heading on the following webpages: http://www.port.ac.uk/application-fees-and-funding/applying-postgraduate/#rd.

 When applying please note the project code – PHBM3771018