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Enhancement of radiation induced cell death using ultrasound stimulated microbubbles

  • Full or part time
    Dr E Harris
    Dr C Box
    Prof K Harrington
  • Application Deadline
    Sunday, November 17, 2019
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

About This PhD Project

Project Description

The Institute of Cancer Research, London, is one of the world’s most influential cancer research institutes. We are committed to attracting and developing the best minds in the world to join us in our mission—to make the discoveries that defeat cancer.

Enhancement of radiation induced cell death using ultrasound stimulated microbubbles
Project Description:
Around 50% of patients with cancer receive radiotherapy as part of their treatment for cancer. Typically, radiotherapy is delivered in 15 to 40 daily doses (fractions) of two Gy. Compelling clinical evidence supports the use of stereotactic body radiotherapy (SBRT) delivered in five fractions or fewer of more than six Gy and has been successfully tested for many tumour types. SBRT has definitive societal and patient benefit; significantly fewer hospital visits increases patient comfort and convenience, and reduces healthcare costs.
The adoption of SBRT in tumour sites adjacent to radiosensitive normal tissues (e.g., head and neck tissues) has been limited because high doses cannot be safely delivered. Mechanical radiosensitisation techniques are attractive because their effects can be localised to the tumour only. Microbubbles injected into the vasculature cavitate when exposed to ultrasound causing capillary wall rupture, cell sonoporation (perforation of the cell membrane) and endothelial cell death. Extensive preclinical evidence supports the use of ultrasound stimulated microbubbles (USMB) as an adjunct therapy administered prior to radiotherapy with equivalent cell death and tumour growth delay at lower doses (2 to 6 Gy) compared to high dose radiation alone (> 8 Gy). Increased cell death was attributed to mechanoacoustic activation of the ASMase-mediated ceramide pathway resulting in rapid downstream apoptosis of endothelial cells. USMB is also known to be vasoconstrictive, providing a potential alternative dual mechanism of action invoking cell death and tumour cell unrepair after an the restriction of blood flow (ischemia), supported by recently published preclinical evidence. Furthermore, there is evidence to suggest that ultrasound and microbubbles (or nanobubbles) promote immune cell infiltration, however, although USMB were shown to improve the efficacy of checkpoint inhibitors, an immune response was not attributable to USMB. (For supporting references please see the full project description.)
Further exploration of the mechanism of action and optimisation of USMB is needed to exploit this promising localised radiosensitisation technique, which is both ultrasound guided and ultrasound targeted.
We are seeking an enthusiastic, inquisitive student who loves to spend time in a lab and design innovative experiments to test scientific hypotheses. This exciting PhD combines aspects of both cancer biology and cancer imaging physics and is well supported by supervisors from both disciplines.
The funded student will: (1) design and demonstrate suitable in vitro techniques to understand the mechanism of action of ultrasound and microbubbles (USMB) on endothelial cells alone and in combination with radiation; (2) assess the response of tumours to USMB and radiation and to understand the mechanism of action of USMB on tumours through the design and execution of suitable in vivo techniques; (3) explore the use of novel targeted microbubbles to enhance tumour control; and (4) study USMB in combination with novel drug therapies

Keywords /Subject Areas:
Radiobiology
Ultrasound
Bioengineering
Cancer biology
Physics
Imaging

Funding Notes

Students receive an annual stipend, currently £21,000 per annum, as well as having tuition fees (both UK/EU and overseas) and project costs paid for the four-year duration. We are open to applications from any eligible candidates and are committed to attracting and developing the best minds in the world.
See icr.ac.uk/phds to apply
Applications close 11:55pm UK time on Sunday 17th November 2019

Candidates must have a first class or upper second class honours BSc Honours/MSc in Biology/Bioenegineering/Biophysics or a related subject



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