PhD student - Unravelling the role of the microRNA cargo of extracellular vesicles in neuron-glia communication in the retina

This work will be performed in the Cellular Communication and Neurodegeneration group led by Prof. Lies De Groef in the Animal Physiology and Neurobiology Division of the Biology Department. Our research focuses on the fundamental understanding of mechanisms of neurodegeneration in the central nervous system. “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. Prof. 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 glaucoma, Parkinson’s and Alzheimer’s disease. You will work in close collaboration with our partners from the Leuven Brain Institute, KU Leuven and UZ Leuven.
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Project

Emerging evidence suggests that extracellular vesicles (EVs) and their miRNA content may function as master regulators of the cellular state of neurons and glia in the central nervous system. Given that miRNAs serve as regulatory nodes with an integrated effect on multiple gene networks, their impact on cellular function is important and the consequences of their dysregulation may be severe. In this project we focus on the role of EV-miRNAs in the signaling between ganglion cells and glia in the retina. The goal is to better understand how EVs and their miRNA cargo mediate intercellular signaling between ganglion cells and glia, and how the dysregulation of this neuron-glia communication leads to loss of homeostasis, glial reactivity and neurodegeneration. With this research, we aim to gain a better understanding of the fundamental biological processes that play a role in intercellular communication in the central nervous system. Via a systems biology approach –comprising miRNA transcriptomics, mRNA transcriptomics and proteomics studies– and functional studies of selected EV-miRNA targets, we aim to identify direct target genes, pathways and biological functions regulated by EV-miRNAs in the retina. Furthermore, this research may also deliver a first proof-of-concept for the manipulation of EV-miRNAs as a strategy to modulate neuron-glia communication and thereby prevent glial reactivity and neurodegeneration.

More specifically, you will perform preclinical research, making use of:

• in vitro/ex vivo models with primary retinal cells, microfluidic devices and organotypic explants
• in vivo mouse models of glaucomatous optic neuropathies, including mouse surgery, intraocular injections, sample collection and dissections
• miRNA/mRNA transcriptomics and proteomics analyses
• bioinformatics pipelines for miRNA target prediction and selection
• functional studies of miRNA:mRNA interactions and miRNA functions
• state-of-the-art techniques for in vivo retinal imaging and electrophysiology (https://www.visioncore.be), detailed morphological phenotyping, microscopy, and molecular-biology analyses

Profile

• You have a master degree in Biology, Biochemistry, Bio-engineering, Biophysics, Biomedical Sciences or equivalent.
• Graduation with distinction (or more).xzMotivation and commitment for pursuing a PhD in the field of neurobiology – ophthalmology.
• Experience in neuroscience and/or cell biology research, bioinformatics, miRNA biology, EV biology, and animal experimentation 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 research applicable to neurodegenerative diseases.
• Start date to be determined (possible from September 1st, 2024)

Interested?

Interested applicants should send a detailed curriculum vitae, a letter of motivation and the contact information of 2 references via the online application tool. Only applications via the online application tool will be considered.

For additional questions, please contact lies.degroef@kuleuven.be.

KU Leuven seeks to foster an environment where all talents can flourish, regardless of gender, age, cultural background, nationality or impairments. If you have any questions relating to accessibility or support, please contact us at diversiteit.HR@kuleuven.be. 

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