This PhD project will be performed in the Neural Circuit Development and Regeneration (NCDR) research group, situated within the Biology Department at KU Leuven and forming a highly qualified and multidisciplinary team with broad expertise and a longstanding track record in the field of axonal regeneration.
The NCDR has a strong interest in defining cellular / molecular mechanisms underlying neurodegeneration, neuroinflammation and regeneration in the eye / visual system of teleost fish and rodents (for more info see : http : / / bio.
kuleuven.be / df / LM / ). The quest for neuroprotective and / or regenerative therapies to tackle neurodegenerative disorders and central nervous system (CNS) trauma is a central theme in our research.
Despite intensive research efforts, induction of regeneration and subsequent functional recovery of the injured mammalian CNS remains a challenge, which makes the search for new pro-regenerative molecules essential.
In contrast to mammals, teleost fish have a remarkable neurogenic and regenerative potential in their adult CNS, making them a preferred model organism in a myriad of comparative studies investigating the underlying mechanisms of successful regeneration.
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 / 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, 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 : http : / / www.visioncore.be / ).
Brain injury and neurodegenerative disorders represent a growing socio-economic problem 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.
Strikingly, up till now, dendrites and their contribution to neuronal regeneration have been largely overlooked. Nevertheless, previous investigations in the host lab suggested that dendrite remodeling is required for spontaneous regrowth of axons in the adult zebrafish CNS.
This PhD project aims, using a combination of innovative approaches, to confirm this refreshing theory at single-neuron level and validate the hypothesis that a reprogramming and relocation of the neuronal energy production machinery is needed for functional circuit restoration.
Thereto, sparsely-labeled transgenic zebrafish lines will be generated to study mitochondrial and metabolic processes at single-neuron level.
Furthermore, potential target molecules involved in mitochondrial dynamics and bioenergetics underlying the different axonal / dendritic regrowth phases will be identified via a single-cell transcriptomic analysis.
Subsequent validation of defined molecules / pathways should generate pivotal insights into how redirecting intra-neuronal energy channeling may promote neuronal repair in the mammalian CNS.
Furthermore, as a candidate
Interested applicants should send a statement of interest, CV and the contact information of 1-2 references to Lieve Moons via mail : lieve.moons kuleuven.be