Self-funded PhD opportunities

The integration of signalling cascades in synovial joints – a role for Dact genes?

  • Application end date: Applications accepted all year round
  • Funding Availability: Self-funded PhD students only
  • Department: School of Pharmacy and Biomedical Sciences
  • PhD Supervisor: Dr Susanne Dietrich

Joint diseases cause much pain and restriction of movement in the elderly, and are on the increase in an ageing population. Frequently, the condition worsens when bony spurs form within the joint. When cartilage and bone first form in the embryo, developing joints are being kept bone-free. Likewise, in healthy joints, the space between the adjoining bones is kept free of hard tissues.

The development of cartilage and bone and the suppression of these processes in the developing joints is controlled by a number of cell-cell communication pathways. How they are integrated inside the cell to achieve a specific outcome is not known. Dact multi-adaptor proteins haven been found to regulate some of these signalling systems. We found that Dact gene expression is associated with the undifferentiated state of cells; specifically, we found Dact genes to be expressed in developing joints. We thus hypothesize that Dacts may integrate signalling cascades to suppress bone formation; thereby allowing the formation and maintenance of joints.

In this project, we will investigate the function of Dact proteins using the developing joints of a chicken embryo as model. We will engineer molecular constructs to misexpress Dacts and to knock down Dact function. Constructs will be introduced into the limbs prior to bone formation, using in-ovo electroporation. Phenotypes will be analysed by in situ hybridisation, immunohistochemistry, skeletal preparations and by quantitative methods such as qPCR. Specifically, we will analyse the state of signalling cascades, and use these data to in collaboration with systems biologists bioinformatically model the integration of signalling cascades in joints. This will allow to better understand erroneous bone formation and to identify potential drug targets.

In addition you will have access to a skills development program run by the university’s Graduate School. The experimental and analytical skills developed during this project will prepare the student well for a future career in academia or industry.

Research Group Web Site: http://www.port.ac.uk/school-of-pharmacy-and-biomedical-sciences/research/ 

Supervisor(s): Dr Susanne Dietrich (School of Pharmacy and Biomedical Sciences)

Funding Status: Self funded - University fees (currently, £13,100 for International Students and £4,052 for Home and EU students). 

Search terms: Cell Biology / Development, Genetics, Molecular Biology; Synovial joints, chicken embryo, Dact genes

How to Apply: To make an enquiry, please contact susanne.dietrich@port.ac.uk.

To apply, please use our standard application forms and follow the instructions given under the ‘Postgraduate Research’ heading on the following webpages:http://www.port.ac.uk/application-fees-and-funding/applying-postgraduate/#rd

When applying please note the project code PHBM3571017