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Clearing protein aggregates from the extracellular space of the brain

  • Full or part time
  • Application Deadline
    Monday, April 15, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Small aggregates of proteins such as amyloid-beta circulate the extracellular space of the brain (ECS) and are thought to be key players in the development of neurodegenerative diseases. The clearance of these aggregates is a fundamental physiological feature of the brain which is poorly understood due to the lack of techniques to study the nanoscale organisation of the ECS. Exciting advances in this field have recently shown that clearance is enhanced during sleep due to a major volume change in the ECS, facilitating the flow of the interstitial fluid. However, this process has only been characterised at a low spatial resolution while the physiological changes occur at the nanoscale. Understanding these processes at a higher spatial resolution requires the development of single-molecule imaging techniques that can study the brain in living animals. The PhD project aims to understand how nanoscale changes in the ECS facilitate clearance of protein aggregates. To achieve this, the successful PhD candidate will perform single-nanoparticle tracking in brain slices and in vivo to characterise key features of the so called “glymphatic” hypothesis. The student will also characterise the clearance of protein aggregates at a single-aggregate level.

We are looking for an enthusiastic PhD student with a background in either physical or biological sciences, willing to work in an interdisciplinary environment studying the brain at the single-molecule level. Experience in biophysics and/or neurosciences will be advantageous.

Applicants are encouraged to contact the PI by email () for informal enquiries prior to submitting the application.

Funding Notes

Applicants should hold or expect to gain at least a 2:1 Bachelor Degree or equivalent in a related subject area. Due to the interdisciplinary nature of the project, applicants may have background studies in either biological or physical sciences.

Funding for 3.5 years is available for UK and European applicants. We regret that we cannot fund candidates from other countries.

References

Varela J, Rodrigues M, De S, Flagemeier P, Dobson CM, Klenerman D, Lee SF. “Optical structural analysis of individual α-synuclein oligomers”. Angewandte Chemie International Edition, 4886–4890 (2018).

Godin A*, Varela J*, Gao Z*, Danne N, Dupuis J, Lounis B, Groc L, Cognet L. “Single-nanotube tracking reveals the nanoscale organization of the extracellular space in the live brain”. Nature Nanotechnology, 12, 238–243 (2017).

Varela J, Dupuis J, Etchepare L, Espana A, Cognet L and Groc L. “Targeting neurotransmitter receptors with nanoparticles in vivo allows single molecule tracking in brain tissue”. Nature Communications, 7:10947 (2016).

Varela J*, Ferreira J*, Dupuis JP*, Durand P, Bouchet D, and Groc L. “Single nanoparticle tracking of NMDA receptors in cultured and intact brain tissue”. Neurophotonics, 3:41808 (2016).

Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O’Donnell J, Christensen DJ, Nicholson C, J. Iliff J, Takano T, Deane R, Nedergaard M, “Sleep drives metabolite clearance from the adult brain”. Science 342, 373–7 (2013).

Nicholson C, Hrabětová S, “Brain Extracellular Space: The Final Frontier of Neuroscience”. Biophysical Journal, 113, 2133–2142 (2017).

How good is research at University of St Andrews in Biological Sciences?

FTE Category A staff submitted: 50.45

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

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