GW4 BioMed MRC DTP PhD Studentship: Understanding and addressing challenges in antibody labelling by new cross-disciplinary techniques for immunoPET imaging and sensing

This project is one of a number that are in competition for funding from the ‘GW4 BioMed MRC Doctoral Training Partnership’ which is offering up to 19 studentships for entry in September/October 2018.

The DTP brings together the Universities of Bath, Bristol, Cardiff and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities.
Supervisory team for this project:
Prof Sofia Pascu (Bath), Dr Chris Pudney (Bath), Dr Stephen Paisey (Cardiff), Prof Paolo Madeddu (Bristol)

Project description:

This programme will enable a new PhD researcher to train in the synthetic and analytical methods required for functionalising new disease biomarkers and the clinical requirements for labelling methodologies as well as the testing tagged antibodies in vitro and in vivo. This introduces life scientists to emerging imaging and sensing technologies suitable for diagnosis and monitoring of disease progress.

The PhD programme is divided into Work Packages (WPs 1-4):
(1) Development of functionalised antibodies in clinical trials of relevance to ischemia and angiogenesis, e.g. annexin V and Avastin; monitoring their environment by fluorescence
(2) Radiolabelling of antibodies with Zr-98 (a radiometal with half-life 78.42 h and 100% EC/positron decay)
(3) System integration from in vitro to in vivo imaging
(4) Career development, pathways to impact and outreach - to secure clinical relevance and likely patient acceptability

Positron Emission Tomography (PET) imaging is a highly sensitive whole-body functional imaging technology. A PET scanner detects femtomoles of artificially produced radioisotopes leading to a quantifiable 3D distribution map of injected radiotracers. ImmunoPET involves radiolabelling biological molecules (e.g. antibodies) to turn them into PET in vivo tracers. Technologies already exist to create and produce antibodies to target almost any biological target or disease, so a generic method to robustly radiolabel antibodies would provide a powerful, broadly applicable diagnostic platform.

Our aim is to optimise the antibody labelling process to increase the efficiency and stability of the labelling processes and minimising the adverse effects on stability and biological activity of the antibodies by combining our GW4 Network’s complimentary expertise. A wide range of electrochemical or optical sensing methodologies are being developed already in our laboratory are suitable for in vitro or even in vivo evaluation of the labelled antibodies and for assessment of their suitability for diagnostics, but the immunoPET approach is novel and a natural expansion from the current view-point.

This multidisciplinary project will be based primarily in Prof Pascu’s laboratories at Bath, where a panel of custom designed Zr chelating molecules will be prepared and their efficiency and stability of Zr binding will be assessed. The method of attachment of the chelator to antibodies will also be optimised with a strong focus on minimising the effect on antibody stability and function. The assessment of the physical properties of the antibody chelator conjugates will be carried out in Dr Pudney’s labs using newly developed (REES) spectroscopy methods. The student will also have access to Zr-89 at PETIC’s state of the art custom built radiochemistry research labs (with Dr Paisey). The student will train in biological assay techniques in the Madeddu labs at Bristol and translate these techniques to the PETIC’s radiochemistry labs to enable the testing of radioactively labelled annexin V. A small proof of principle in vivo PET imaging study of the lead Annexin V will also be carried out at PETIC in Prof Madeddu’s hind limb ischemia model.There is experience and focus on perfusion imaging in the team and so the it would be of interest to compare the perfusion images to the apoptosis images. This will tackle unmet clinical needs in non-communicable diseases diagnosis and therapy and provide a general solution to NCD challenges.

IMPORTANT: In order to apply for this project, you should apply using the DTP’s online application form. More information on the application process may be found here: http://www.gw4biomed.ac.uk/projects-2/for-students/

APPLICATIONS OPEN ON 25 SEPTEMBER AND CLOSE AT 17:00 ON 24 NOVEMBER 2017.

You do NOT need to apply to the University of Bath at this stage – only those applicants who are successful in obtaining an offer of funding from the DTP will be required to submit an application to study at Bath.