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  Imaging the local accumulation and clearance of protein aggregates in the extracellular space of the brain in Alzheimer’s disease models.


   School of Biology

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  Dr J Varela, Prof F Gunn-Moore  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

Small aggregates of misfolded proteins are thought to be the main cause for cellular death in a wide variety of neurodegenerative diseases. A large fraction of these aggregates (particularly in the case of amyloid beta) are present in the extracellular space, which despite being almost 20% of the brain volume, is relatively unexplored due to the lack of techniques that can work at the right spatial resolution in physiological conditions. Taking advantage of the techniques we have recently developed; the PhD project aims to study the way protein aggregates accumulate and are cleared from this convoluted space. This will have deep consequences in the way we understand the spreading of neurodegeneration along the brain, particularly during early stages of the disease.

We are looking for an enthusiastic PhD student with a strong 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 may contact the PI by email ([Email Address Removed]) for informal enquiries prior to submitting the application.


Funding Notes

This position is fully funded (for 3.5 years) by Alzheimer’s Society for UK and ERC Starting Grant “BrainNanoFlow”.

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

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).

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