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Post-Doc Project
Noninvasive Drug Delivery to Treat Alzheimer's Disease

*Closing date of 16 July 2017 (Midnight BST)
Starting date is flexible

*the closing date has been changed from 2 July to 16 July

SUMMARY

We are seeking a post-doc who would like to use an exciting molecular delivery technology developed in our laboratory to treat Alzheimer’s disease modelled in a transgenic experimental model, and explore other therapeutic or scientific uses for this technology. The research is funded by Alzheimer's Research UK.

Research Assistant: £31,740 - £33,370 per annum
Research Associate: £36,070 – £43,350 per annum* (Maximum starting salary: £37,020)
Full time, fixed term appointment for up to 36 months

Job reference number: EN20170149FH

Closing Date: 16 July 2017 (Midnight BST)
Note: the closing date has been changed from 2 July to 16 July

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Project in Detail

"A Neurotechnology to Deliver Drugs Across the Blood-Brain Barrier and Treat Alzheimer's Disease"

The blood-brain barrier (BBB), which prevents large molecules passing from the blood into the brain is a major hurdle to treating brain diseases. One of the main strategies for the treatment of Alzheimer's disease are to limit production or aggregation of the amyloid β peptides implicated in Alzheimer’s disease. While early versions of drugs were successful in vitro, an inability to penetrate the BBB left them unsuccessful in in vivo models. Newer small drugs, designed to cross the BBB, suffer from reduced potency and specificity, introducing the probability of harmful off-target effects due to the higher doses required. 

We have shown that non-invasively administered ultrasound pulses can produce controlled, temporary changes to BBB permeability (Choi JJ et al., PNAS. 2011). The purpose of this is to develop and test a new short-pulse ultrasound delivery method (Pouliopoulos AN et al., J Acoust Soc Am. 2016) for the treatment of Alzheimer’s and evaluate its performance in reducing/halting the progression, modelled in transgenic experimental models. In allowing large molecule drug delivery to the brain, or targeted small molecule delivery at lower doses, this has the potential to revive previously shelved therapies that have shown great promise for the treatment of Alzheimer's disease.

Team

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Dr. James Choi (PI)
Department of Bioengineering

Dr. Choi will supervise the ultrasound portion of your work and will be your primary supervisor. He is also the principal investigator of this study.

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Dr. Magdalena Sastre (Co-I)
Department of Medicine

Will supervise the Alzheimer's disease portion of your work. She will train you to manage the transgenic colony, conduct behavioural studies, and analyse tissue.

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Prof. Simon Schultz (Co-I)
Department of Bioengineering

Will supervise the neuroscience portion of your work. His Neural Coding laboratory neighbours Dr. Choi's laboratory and they share facilities.

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Matthew Copping
PhD Student

Matthew will be working on the ultrasound and physics portion of the device. You will be working very closely with Matthew throughout the 3 years.

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Tiffany Chan
PhD Student

Tiffany is working on a separate project to develop neurologically active nanoparticles.

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Sophie Morse
PhD Student

Sophie has led the early work on the development of ultrasound brain drug delivery in our laboratory. She is working on a separate project focussed on cancer imaging and therapy.

The Technology

We have constructed an in vivo bench-top ultrasound device that noninvasively and locally delivers drugs into the brain. We have a targeting software that moves the ultrasound beam to the region we'd like to deliver drugs to. We then administer microbubbles into the bloodstream via an intravenous injection. These microbubbles are originally in an inactive form. We then apply short, low-intensity pulses onto the target brain tissue, which causes the microbubbles to volumetrically expand and contract. This produces mixing within or mechanical stress on the cerebral capillaries, which alters the blood-brain barrier permeability. We then administer the drug to take advantage of this short duration of permeability change.

For more information on the technology, read the following papers in order:

  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):16539-44. 2011. Link
  2. Pouliopoulos AN, Li C, Tinguely M, Garbin V, Tang MX, Choi JJ. Rapid short-pulse sequences enhance the spatiotemporal uniformity of acoustically driven microbubble activity during flow conditions. J. Acoust. Soc. Am.140;2469. 2016 Link

The Applicant

We are looking to appoint someone to work with experts in Neuroscience, Engineering, Physics, Chemistry, and Medicine while having the unique experience of interacting with clinicians and industry. It would be advantageous to have knowledge of transgenic experimental models of neurodegeneration, and skill with standard biological techniques (e.g., western blotting, immunohistochemistry, microscopy).

Applicants should have, or nearly completed a PhD in neuroscience or related discipline; or can demonstrate equivalent research, industrial or commercial experience.