We specialise in medical, biological, health and social care sciences. We currently have over 250 students in programmes engaged in research. The Research Excellence Framework (REF), a new national assessment of research at UK universities has ranked St George’s, University of London, as fourth for impact of its research on the global community.

HIV research

We offer a number of programmes with wide-ranging opportunities for translational research. We offer PhD study opportunities as well as MPhil, MD(Res) and a number of our taught Master's courses includes a research project. A core training course for research students supports the acquisition of more generic research skills and provides opportunities for peer-group support.

Read more about research degrees at St George's

Studentships

We currently have one studentship available.

Molecular and Clinical Science Studentship, Vascular Biology Centre

Title of Studentship - Raf kinases and cardiac ECs: Characterising Raf inhibition in chronic hypertension

This is a funded studentship (at BHF rates) for three years and will include fees and a stipend

Cardiac endothelial cell (EC) dysfunction is the underlying feature of diastolic heart failure, a poorly understood disease. The ERK1/2 cascade is cytoprotective and regulates cellular proliferation, and is, therefore, one key pathway targeted in cancer. Inhibitors of the uppermost ERK1/2 cascade kinases (Raf kinases) are in development. However, their effects on cardiac ECs generally, or in the context of diseased and remodelled hearts are unknown. This PhD studentship aims to characterise EC Raf signalling and to determine whether a novel Type-2 Raf inhibitor is cardiotoxic and accelerates cardiac EC dysfunction and heart failure in the context of angiotensin-II-induced hypertension.

Failing hypertensive hearts are adversely remodelled and extensively fibrotic, a response attributed in part to myocardial capillary rarefaction and endothelial cell (EC) dysfunction. The ERK1/2 cascade is cytoprotective and promotes cell proliferation, and is thus a key signalling pathway targeted in cancer.  Inhibitors of the uppermost ERK1/2 cascade kinases (Raf kinases) are used clinically. However, their effects on EC Raf signalling generally, or on cardiac ECs from normal or diseased hearts are unknown. Our preliminary data indicate that Raf kinase inhibitors suppress cardiac ERK1/2 signalling and this could dampen cytoprotective EC signals. The hypothesise for this PhD project is that Type 2 Raf inhibitors that completely suppress cardiac EC Raf signalling promote progression to heart failure, particularly in the context of diseases such as hypertension, due to a loss of cytoprotective mechanisms. Specifically, this studentship aims to determine if a novel Type-2 Raf inhibitor accelerates cardiac EC dysfunction using in vitro and ex vivo cell cultures of human ECs and 3-dimensional organo-cultures. Contextual relevance will be established using in vitro angiotensin-II (AngII) challenge, alongside an in vivo murine AngII hypertension model. The data will provide novel and important mechanistic information for cardiac EC Raf signalling, and identify whether Type-2 Raf inhibitors are detrimental to cardiac function in hypertension.

This project will utilise a range of cell biology, molecular biology and protein biochemistry techniques focused towards endothelial and cardiac biology. In vivo studies will also be conducted using wild-type mice subjected to hypertension.

This project will involve the use of animals and you will be required to get an animal licence to successfully undertake this project (funds are allocated).

Specific techniques to be used and in which the student will be trained include:

In vivo and ex vivo studies. 

  • Schedule 1 and licensed procedures suitable for harvesting hearts for perfusion or cell preparations.
  • Mouse echocardiography (ECHO)
  • Administration of anaesthetics
  • Cardiac histology and cardiac EC signalling in situ
  • Surgical implantation of minipumps and administration of analgesics
  • Ex vivo culturing of tissues for 3D tissue manipulation

Cell biology, molecular biology and protein biochemistry. 

  • Cell culture techniques (including transfection and expression manipulation) for primary endothelial cells
  • Subcellular fractionation and protein preparation for immunoblotting
  • Gel filtration and ion-exchange FPLC
  • Immunoblotting techniques and densitometric analysis of data
  • Bioinformatics for gene and protein expression studies
  • RNA preparation and quantitative PCR techniques
  • Immunofluorescence microscopy
  • Protein kinase assays

 

The student will be required to attend training courses offered by the graduate school.

Supervisors - Dr Daniel Meijles and Professor Angela Clerk (University of Reading)

Queries regarding the project can be sent to DThis email address is being protected from spambots. You need JavaScript enabled to view it.

To apply - please complete the application form and ask your referees to complete the reference form 

Application forms and reference forms should be completed electronically and emailed to This email address is being protected from spambots. You need JavaScript enabled to view it.

CLOSING DATE IS 1200 ON FRIDAY 12 JULY 2019


Last Updated: Tuesday, 26 March 2019 15:31