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Development of a noninvasive and localised blood-brain barrier opening system for the treatment of Alzheimer’s Disease

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  • Full or part time
    Dr Choi
    Dr Sastre
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

This project is one of 11 studentships on offer in the Imperial College EPSRC Centre for Doctoral Training in Neurotechnology for Life and Health

Supervisors: James Choi (Bioengineering), Magdalena Sastre (Medicine)

Current Alzheimer’s Disease (AD) drugs treat symptoms, but not the underlying disease process. Despite the availability of neurologically potent drugs (eg, inhibitors, antibodies), cerebral capillaries (ie, blood-brain barrier) block their entry into the brain.

The student will design, construct, and characterise a non-invasive ultrasound-based technology that drives systemically administered microbubbles into volumetric oscillations. This technology exerts mechanical stress from within the capillaries to increase permeability and allow drugs safe passage into the brain. The student will then use this technology to deliver drugs in transgenic AD mice, reduce AD pathology, and improve cognitive function.

For further details, visit http://www.nsblab.org/phd-project-2016-adt.

The CDT programme is not a standard PhD programme. Throughout the 4 years, there is considerable emphasis upon multidisciplinary and transferable skills, through centre activities beyond the individual research project. The programme cannot be taken without the first (MRes Neurotechnology) year, as it is an integral part of the overall programme.

Applicants should have (or expect to obtain) a first or upper second class degree (or non-UK equivalent) in an engineering or physical science subject. Students with a biological and medical sciences background may be considered, but candidates must have sufficient quantitative skills to thrive in the programme. You should be looking for a challenging, multi-disciplinary PhD at the interface of neuroscience and engineering.

To apply online, visit www.imperial.ac.uk/neurotechnology/cdt/apply/

If you have questions or would like further information about the project, we encourage you to contact the supervisors directly before making your formal application.

Funding Notes

Studentships pay UK/EU tuition fees, stipend and a generous consumables and travel fund for the duration of the programme (one year of MRes and 3 years of PhD).

Places are open to UK and EU applicants only.

References

[1] Choi JJ, Selert K, Vlachos F, Wong A, Konofagou EE. Noninvasive and localized neuronal delivery using short ultrasonic pulses and microbubbles. Proc Natl Acad Sci U S A. 108(40) 2011.

[2] Choi JJ, Selert K, Gao Z, Samiotaki G, Baseri B, Konofagou EE. Noninvasive and localized blood-brain barrier disruption using focused ultrasound can be achieved at short pulse lengths and low pulse repetition frequencies. J Cereb Blood Flow Metab. 31(2) 2011.

[3] Pouliopoulos A, Bonaccorsi S, Choi JJ. Exploiting flow to control the in vitro spatiotemporal distribution of microbubble-seeded acoustic cavitation activity in ultrasound therapy. Phys Med Biol. 59(22) 2014.

[4] Sastre M et al. Nonsteroidal anti-inflammatory drugs repress beta-secretase gene promoter activity by the activation of PPARgamma. Proc Natl Acad Sci U S A. 103(2) 2006.

[5] Mi W, Pawlik M, Sastre M, et al. Cystatin C inhibits amyloid-beta deposition in Alzheimer's disease mouse models. Nat. Genet. 39(12) 2007.

[6] Parr C, Carzaniga R, Gentleman SM, Walter J, Van Leuven F, Sastre M. Glycogen synthase kinase 3 inhibition promotes lysosomal biogenesis and autophagic degradation of the amyloid-β precursor protein. Mol Cel. Biol. 32(21) 2012.

How good is research at Imperial College London in General Engineering?

FTE Category A staff submitted: 33.50

Research output data provided by the Research Excellence Framework (REF)

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