EXTRACELLULAR VESICLES AND NEURON-GLIA COMMUNICATION IN NEURODEGENERATION

16 June 2021

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Interested?

For more information please contact Mrs. Lies De Groef, mail: lies.degroef@kuleuven.be.You can apply for this job no later than July 30, 2021 via the online application tool

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(ref. BAP-2021-494)

Apply before 30 July 2021

This work will be performed in a new research group that will be established by Dr. Lies De Groef in the Animal Physiology and Neurobiology Division of the Biology Department, starting from October 1, 2021. Our research focuses on the fundamental understanding of mechanisms of intercellular communication in the central nervous system, more specifically between neurons and glial cells. We study these interactions both under physiological conditions and in the context of neurodegeneration.

“The eye as a window to the brain” is the central theme of our research. We focus on the inter-relatedness of neurobiology and ophthalmology and exploit this cross-over of disciplines to enrich fundamental research into central nervous system function. A greater understanding of the cellular and molecular mechanisms governing brain function are key to unlock novel therapeutic strategies for central nervous system diseases – which represent a rising burden –, and the visual system offers unique possibilities to tackle these research questions. Dr. De Groef and her team have more than 10 years of experience/expertise in neurodegeneration and -inflammation research in the visual system, in vivo retinal imaging, electrophysiology and visual behavior testing, and disease mechanisms of Parkinson’s and Alzheimer’s disease

Project

Extracellular vesicles have emerged as important mediators of intercellular communication. By delivering their cargo, including protein, lipid, RNA and/or DNA, to adjacent and distant cells, extracellular vesicles have the capability of modifying the recipient cell phenotype. Extracellular vesicles have a proposed role in neuron-neuron, neuron-astrocyte, and neuron-microglia signaling, and thereby modulate a.o. neuroimmune function, trophic support, myelination, neurite outgrowth, neuronal survival, and synaptic activity. Extracellular vesicles are also potent mediators of intercellular communication between immune cells, microglia, macroglia and their microenvironment, and they can propagate a robust inflammatory reaction. Finally, extracellular vesicles are believed to be involved in the spreading of neurotoxic proteins (protein aggregates) in neurodegenerative diseases such as Parkinson’s, Alzheimer’s, Creutzfeldt-Jacob, and amyotrophic lateral sclerosis. In these conditions, a prion-like disease progression has been proposed, and extracellular vesicles appear to be the major vehicles that shuttle toxic proteins out of the cell and seed protein aggregation in acceptor cells.

The aim of this PhD project is to unravel mechanisms of intercellular communication in the central nervous system, with a focus on the role of extracellular vesicles as messenger nano-organelles in neuron-glia interactions. We want to expand our basic knowledge of extracellular vesicle biology, and to understand the role of extracellular vesicle-mediated intercellular transport and communication in neuroinflammation and protein propagation. We are looking for a PhD student to investigate (i) the role of extracellular vesicles in cell-cell communication during neuroinflammation, with a focus on innate immune cells and macroglia; (ii) the role of extracellular vesicles in prion-like spreading of protein aggregates, more specifically alpha-synuclein; and (iii) the potential interaction between the roles of extracellular vesicles in neuroinflammation and protein propagation.

To address these research questions, we plan an in-depth characterization of the underlying cellular mechanisms via a combination of in vitro mechanistic and in vivo validation studies. All research runs within the ‘Vision Core Leuven’, a preclinical animal platform which brings together cutting-edge technologies within the field of ocular imaging, electrophysiology and visual function testing in laboratory animals (https://www.visioncore.be). Furthermore, we employ state-of-the-art techniques for detailed morphological phenotyping, including confocal/multiphoton/light-sheet microscopy, optical clearing and time-lapse imaging, and longitudinal and post-mortem morphometrical analyses to follow inflammatory and de/regenerative processes. Besides, ex vivo/in vitro retinal tissue/cell cultures, flow cytometry and (single-cell) omics approaches are available to further study the cellular and molecular pathways.

Profile
  • You have a master degree in Biology, Biochemistry, Bio-engineering, Biophysics, Biomedical Sciences or equivalent.
  • Graduation with distinction (or more).
  • Motivation and commitment for pursuing a PhD in the field of neurobiology – ophthalmology.
  • Experience in neuroscience and/or cell biology research, animal experimentation, molecular biology and/or microscopy skills is a plus.
  • Very good knowledge of English, both orally and written.
  • Other required competences: proactive, communicative, accurate, able to work independently and in team, good organization and coordination skills, eager to learn.
Offer
  • A dynamic environment with opportunities for further development and training, and collaboration with many other research groups and core facilities in KU Leuven and abroad.
  • The opportunity to be part of a dynamic team and provide a meaningful contribution to neuroscience researchapplicable to neurodegenerative diseases.
  • Start date to be determined (possible from October 1, 2021)