Intraneuronal energy channeling as a prerequisite for functional CNS repair

(ref. BAP-2022-442)

Laatst aangepast : 21/06/2022

This PhD project runs within a joint effort from two internationally recognized research groups, that form a highly qualified and multidisciplinary team with broad expertise and a longstanding track record in the field. The PhD project will be performed in two laboratories situated within the Biology Department (Group W&T) at KU Leuven, under supervision of Profs. L. Moons and K. Farrow. Dr. L. Moons is heading the Neural Circuit & Regeneration group (https://bio.kuleuven.be/df/lm). She is an expert in studying neuronal survival and axonal regeneration in the visual system of mouse and teleost fish and has an established expertise in in-depth morphological, functional and behavioral phenotyping of animal injury/disease models, including transgenic zebrafish and mice, models of axonal injury and advanced microscopic analysis of neurite regrowth. Her team also provides the competence to perform ex vivo retina and brain explant cultures, cell sorting and (single-cell) omics approaches and pharmacological/genetic manipulations to study the (sub)cellular and molecular pathways underlying neuroprotection/regeneration. Dr. K. Farrow, who leads the Visual Neural Circuits lab (https://www.nerf.be/research/nerf-labs/karl-farrow-lab or https://www.farrowlab.com), shows proficiency in neurophysiology of the retina and superior colliculus and strengthens the team with his expertise of in vivo two-photon (calcium) imaging, quantitative anatomy and viral tracing techniques. Thus, this project elegantly bridges the common research interests of both both teams and provides a superb training environment. To tackle our research questions, we follow a multidisciplinary approach in which advanced in vivo ocular imaging technologies and visual function tests are being combined with detailed morphological phenotyping, using confocal/two-photon/light-sheet microscopy, optical clearing and time-lapse imaging, and longitudinal and post-mortem morphometrical analyses to follow regenerative processes. Besides, ex vivo/in vitro retinal tissue/cell cultures, state-of-the-art opto- & chemogenetic, cell sorting and (single-cell) omics approaches are available to further study the cellular and molecular pathways underlying neuroprotection/regeneration. 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 (see: https://www.visioncore.be).

Project

Brain trauma and neurodegenerative disorders represent a critical socioeconomic challenge in our aging society, partly because the central nervous system (CNS) of mammals has a limited regenerative capacity. Most of the injured neurons die, and the few survivors fail to extend their axons beyond the damaged site. Despite many years of research, functional circuit regeneration is still not possible. To tackle this challenge, our teams combine complementary animal models: zebrafish, that display robust regeneration of the CNS after injury, and mice, which like humans do not. We recently revealed an antagonistic axon-dendrite interplay in adult zebrafish neurons, wherein the retraction of dendrites is needed for effective axonal repair, and also showed that the distribution and morphology of mitochondria change in the different neuronal compartments during injury-induced axonal regeneration. Based on these observations, we hypothesize that the inter-dependency of dendritic and axonal regrowth is resource limited. To test our hypothesis, we are investigating how the allocation of energy production shifts in single neurons among distinct compartments during injury-induced regrowth in both zebrafish and mice. Using a combination of bioinformatic, molecular and imaging approaches, we aim to uncover a set of molecular targets and mechanistic principles that support functional circuit repair in the mammalian CNS.

The PhD project specifically aims at characterizing local changes in mitochondrial dynamics and metabolic processes in adult mouse RGCs during injury-induced regeneration using a combination of innovative approaches, such as retina and brain explants in an ex vivo microfluidic set-up, sparse neuronal labeling in vivo, ex vivo and in vivo imaging using confocal, two-photon and light-sheet microscopy. Furthermore, based on single-cell RNA sequencing and bioinformatic analyses, a set of potential target molecules involved in mitochondrial dynamics and bioenergetics underlying axonal/dendritic regrowth phases will be validated.

Profile

• You have a master degree in Biology, Biochemistry, Bio-engineering, Biophysics, Biomedical Sciences or equivalent.
  
• You have good knowledge of the English language, both spoken and written.
  
• You have a strong interest in neurobiology – ophthalmology.
  
• You have strong interest in neurodegenerative diseases and repair strategies
  
• Any prior experience in imaging, histology, molecular biology or omics analyses is an asset.
  

Furthermore, as a candidate, you are well organized and eager to learn new technologies, you are creative and goal oriented, you have good social and  communicative skills, you are flexible, you are a team player and enthusiastic to obtain new expertise.

Offer

• An exciting working environment where quality, professionalism and human contacts are paramount.
• The opportunity to be part of a dynamic and collaborative team and provide a meaningful contribution to the identification of molecular targets to enhance regenerative growth and reconnection, applicable to neurodegenerative diseases and promoting neural repair.

Interested?

Interested applicants should send a detailed Curriculum Vitae, a concise letter of motivation and the contact information of 1-2 references to Lieve Moons via mail: [email protected].

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 [email protected].