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Seed Funding of the University Research Fund (BOF, 01/07/2026 - 30/06/2030) for a joint PhD student between the Experimental Neurobiology Unit and the Bio-Imaging Lab.

Key µNEURO members involved: Prof. Tommas Ellender, Prof. Daniele Bertoglio

Abstract

Modern genetic and other technologies are creating new therapeutic opportunities for inherited neurodegenerative disorders such as Huntington's disease (HD). HD is caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene, leading to production of a mutant huntingtin (mHTT) protein. Many emerging therapeutic strategies aim to reduce mHTT levels in the brain. However, most current approaches are non‑allele‑selective and therefore also lower the normal wild‑type huntingtin (wtHTT) protein. Because wtHTT is essential for neurodevelopment and provides critical neuroprotective functions in the adult brain, the consequences of its partial reduction remain insufficiently understood and may introduce unintended functional impairments. Indeed, a much deeper understanding is needed regarding the effects of HTT and mHTT in the developing brain as well as the interplay between compensatory and pathogenic mechanisms taking place during the prodromal phases of HD. In this collaborative project, we will characterize the acute and long‑term effects of partial HTT lowering on striatal circuits and their relevance for HD pathophysiology. Using a dedicated mouse model of controlled HTT reduction, combined with advanced non‑invasive functional MRI and in vivo and in vitro electrophysiological recordings, we will map the impact of HTT modulation across multiple spatial and temporal scales. The findings will clarify how partial wtHTT loss affects the functional integrity of basal ganglia circuits and help define potential thresholds for safe and tolerable HTT lowering in the brain.

FWO PhD Fellowship Fundamental Research (01/11/2025 - 31/10/2029) of Marion Decrop 

​Key µNEURO members involved: Prof. Daniele Bertoglio & Prof. Marleen Verhoye (Bio-Imaging Lab); Prof. Tommas Ellender (Experimental Neurobiology Unit)

Abstract

Huntington's disease (HD) is an incurable hereditary neurodegenerative disorder caused by an expansion of a CAG trinucleotide repeat in the huntingtin (HTT) gene, leading to the accumulation of mHTT aggregates. While the precise mechanisms related to the impairment of the direct and indirect dopaminergic pathways of the basal ganglia remain unclear, recent evidence indicated somatic instability (SI) as a key driver of HD pathogenesis. In particular, the DNA mismatch repair gene MSH3 has been identified as one of the major players to promote SI, as recent work indicated that modulation of Msh3 leads to significantly reduced mHTT aggregate formation. However, it remains elusive whether modulation of Msh3, and thus SI, could improve the brain's functional activity, especially within the severely affected dopaminergic pathways. In this project, I will examine the functional integrity of the direct and indirect dopaminergic pathways and assess the longitudinal effect of global Msh3 knockout for the treatment of HD. By combining advanced pharmacological MRI with electrophysiology, proteomics, and molecular analyses in a multidisciplinary approach, this will be the first project to provide an understanding of the impact of targeting somatic instability on the functional integrity of the dopaminergic pathways. The outcomes of this research will provide key insights for the development of novel therapies aimed at SI, not only for HD but also for other disorders involving CAG repeats.

Funded by the University Research Fund (BOF) of the University of Antwerp (01/06/2025 - 31/05/2027)

Key µNEURO members involved: Prof. Tommas Ellender, Prof. Sarah Weckhuysen, Dr. Stijn in 't Groen

Abstract

This application is to request funding to purchase a state-of-the-art 3D Multi-Electrode Array platform (MEA) to enable electrophysiological recordings from complex electrically excitable tissues and organoids. To study the electrophysiological properties of excitable cells, patch-clamping is deemed the gold-standard, but it is an extremely labor-intensive and invasive technique and limited to short-term measurements of individual or small numbers of cells at a single time point. In contrast, MEAs enable high-throughput non-invasive longitudinal real‐time measurements of functional cellular networks without disrupting important cell-cell contacts whilst allowing for the recording of many hundreds to thousands of cells simultaneously therefore providing greater insight into important physiological processes. Current MEA systems at the University of Antwerp only include setups using arrays of planar electrodes which are not suitable for recording from the complex tissues such as brain and cardiac organoids or tissue sections as the electrodes do not get close to the active cells. In contrast this 3D MEA system consists of arrays of ~0.1 mm raised electrodes which allow for repeated recordings from active cells within these organoids and tissues which can be grown under various experimental conditions. There is an urgent need as increasing numbers of research groups at the University of Antwerp use such tissue models but have no means to record from them. The 3D MEA platform is the most suitable instrument and will help many groups to functionally elucidate the pathomechanisms of neurological and cardiac disorders as well as provide the opportunity to rapidly screen large drug libraries.

Supported by the University Research Fund (BOF) of the University of Antwerp, 01/06/2025 - 31/05/2027

Key µNEURO members involved: Prof. Marleen Verhoye & Prof. Daniele Bertoglio (Bio-Imaging Lab); Prof. Rose Bruffaerts (Experimental Neurobiology Unit); Prof. Ben Jeurissen & Prof. Jan Sijbers (Imec - Vision Lab)

Abstract

We propose the replacement and upgrade of the Bruker Gradient/Shim Coil B-GA12S with the Bruker Gradient/Shim Coil B-GA12S HP for the BIOSPEC 94/20 Bruker MRI scanner at the Bio-Imaging Lab at ��������Ƶ. The Gradient/Shim coil is essential for conducting MRI experiments on our 9.4T MRI system, and the current coil has already been in service for 19 years meaning that it reached end of life and necessitates an upgrade. This new coil will significantly enhance the performance of the MRI system and help maintain the Bio-Imaging Lab's position as a one of the (inter)national leaders in advanced small-animal MR imaging. The upgraded Gradient/Shim Coil will improve the 9.4T MRI system's capabilities, offering superior performance through its water-cooled, actively shielded gradients with integrated higher-order shims. These features are specifically designed to support experiments requiring high duty cycles, as well as high gradient and shim field strengths. The increased shim field strength will address the susceptibility challenges typical of high B0 magnets, enabling fast distortion-free EPI recordings of the entire animal brain. Furthermore, the reduced linearity errors of the gradients are crucial for precise tissue property measurements and accurate data quantification. This upgrade will directly benefit numerous ongoing and upcoming research projects led by faculty members and collaborators, enhance the lab's research capabilities, attract further partnerships, and boost opportunities for valorisation and application of the research outcomes.

This project is funded by the University Research Fund of the University of Antwerp (BOF-Impuls, 01/01/2025 - 31/12/2028).

With three joint PhD students, this project relies on an intensive collaboration between the imec-Vision Lab, Bio-Imaging Lab and the Laboratory of Cell Biology and Histology.

Key µNEURO members involved: Prof. Jan Sijbers, Prof. Daniele Bertoglio, Prof. Winnok De Vos, Prof. Ben Jeurissen, Prof. Marleen Verhoye

Abstract

Neurodegenerative diseases are rapidly emerging as an insidious epidemic, presenting a significant challenge due to their limited therapeutic options. While Magnetic Resonance Imaging (MRI) has become indispensable for monitoring disease progression in both clinical and preclinical settings, its capacity to capture the underlying pathophysiological mechanisms remains constrained. Our preliminary work has demonstrated that sophisticated contrasts obtained from diffusion weighted MRI (DWI) or arterial spin labeling (ASL) hold promise in detecting subtle microstructural and perfusion alterations, respectively. However, their sensitivity and resolution are hindered by imaging time limitations. Light sheet microscopy (LSM) can complement these in vivo imaging modalities with molecular information, but equally suffers from suboptimal image quality. Recognizing the complementary potential of these modalities and acknowledging their existing limitations, our intent is to propel multimodal brain imaging forward by enhancing MRI and LSM images through model-based superresolution reconstruction. Our proposed framework is built on the premise that isotropic high-resolution images can be estimated from a collection of oblique lower resolution images. We plan to accomplish this by employing iterative algorithms and leveraging deep learning techniques, rendering the calculations more efficient. Specifically, we seek to develop superresolution reconstruction frameworks that will enable precise estimation of neuronal density from DWI, reproducible estimation of cerebral blood flow from ASL, and comprehensive quantification of sub-cellular structures from LSM. Upon successful development, we will validate these enhanced imaging techniques using a well-characterized mouse model for Huntington's Disease, a condition that necessitates a comprehensive high-resolution approach. By correlating the different imaging modalities at high resolution, we intend to enable ultra-high-content imaging of the brain, ultimately revealing intricate relationships between measured parameters and pathological defects at an individual level. Our team comprises experts from diverse disciplines, including image processing and modeling (VLAB), neuro-oriented MRI (BIL), and advanced cell biology coupled with microscopy (CBH). This multidisciplinary collaboration positions us ideally to accomplish our ambitious objectives. Moreover, as members of the µNEURO research excellence consortium, along with our roles as representatives of core facilities and coordinators of two valorization platforms, we have established a robust platform for amplifying the impact of our project. This strategic positioning ensures that the outcomes of our research will have a far-reaching effect in advancing our understanding of neurodegenerative diseases through cutting-edge imaging technologies.

The MSCA Doctoral Network IQ-BRAIN is coordinated by the imec-Vision Lab, in close collaboration with the Bio-Imaging Lab. 

The project is funded by the European Union (01/12/2024 - 30/11/2028, Grant Agreement No. 101169519). 

Key µNEURO members involved: Prof. Jan Sijbers, Dr. Arjan den Dekker, Prof. Ben Jeurissen, Prof. Marleen Verhoye, Prof. Daniele Bertoglio, Dr. Liesbeth Vanherp

Project website: www.iq-brain.eu​

Abstract

MRI is a key methodology in modern neuroimaging, but conventional MRI relies on visual interpretation of intensity differences in the images, which is heavily dependent on scanner settings. Quantitative MRI (qMRI) is an attractive alternative MRI method that allows quantitative measurement of physical tissue parameters, enabling objective comparison between patients and across time. Moreover, qMRI facilitates early detection of pathological changes in the brain resulting from neurological disorders such as multiple sclerosis. Unfortunately, and despite the demonstrated potential in research settings, the implementation of qMRI in routine clinical practice remains limited due to long scan and post-processing times. While recent developments in artificial intelligence have the potential to accelerate and improve medical imaging pipelines, reduced transparency about the underlying processes, the lack of training data sets and limited information about the accuracy of the results has limited its use for clinical qMRI applications so far. In IQ-BRAIN, we propose a unique research and training programme that tackles this urgent need for improved and accelerated qMRI methodology for neuroimaging applications. By integrating both physics-based models and trustworthy artificial intelligence methods along the qMRI pipeline, our innovative approach combines the best of both worlds. IQ-BRAIN will prepare the next generation of qMRI specialists trained in the different aspects of the qMRI-neuroimaging pipeline, that can bridge the gap between qMRI method development and clinical need. Through a training programme of network-wide events, international secondments, and strong interaction between partners from academia, industry and hospitals, IQ-BRAIN offers early-stage researchers a rich combination of knowledge, expertise and essential transferable skills that prepares them for a thriving career as R&D professionals in the qMRI field.

FWO PhD Fellowship Strategic Basic Research (01/11/2024 - 31/10/2028) of Noor Zonnekein

Key µNEURO members involved: Prof. Sarah Weckhuysen (Translational Neurosciences / VIB-CMN) & Prof. Tommas Ellender (Experimental Neurobiology Unit)

Abstract

Developmental and epileptic encephalopathy (DEE) caused by pathogenic variants in the KCNQ2 gene is a severe, early-onset neurological disorder characterised by neonatal seizures and developmental delay. Although seizures can be controlled in many KCNQ2-DEE patients with anti-seizure medication, there are no treatments that address the developmental problems. As a result, these children require intensive care for the rest of their lives. Given the slow and expensive nature of the drug discovery process, the prospects of providing safe and effective treatments for KCNQ2-DEE patients in a short term remain low. In this project, I will combine state-of-the-art in vitro brain organoids with transcriptomic technology, innovative electrophysiological readout systems and a computational prediction strategy to develop a drug screening platform to repurpose well-characterised FDA-approved drugs. This approach will provide unprecedented insight into the underlying molecular pathology of KCNQ2-DEE together with the potential to identify novel drug candidates for this disorder. If successful, the drug screening platform can be extended to other neurodevelopmental disorders for drug compound identification.

At the University of Antwerp, two Doctoral Candidates will be hosted in the Laboratory of Experimental Hematology of Prof. Peter Ponsaerts, in close collaboration with two µNEURO groups: the Bio-Imaging Lab and the Laboratory of Cell Biology and Histology.

​The project is funded by the European Union (01/09/2024 - 31/08/2028).

Key µNEURO members involved: Prof. Marleen Verhoye, Prof. Winnok De Vos

Project website: 

Abstract

Over the past two decades, cells isolated from human perinatal (or birth-associated) tissues (amniotic membrane, umbilical cord tissue and cells from amniotic fluid), have been shown to provide tremendous pro-regenerative activities. Amongst others, the application of these cells or of components of their secretome, including extracellular vesicles (EVs), have been found to improve myocardial infarction (MI), ischemic stroke (IS) and multiple sclerosis (MS) symptoms in various animal models. Currently, cell-free therapies represent a frontier for innovation in regenerative medicine for clinical unmet needs, however, very few scientists are trained for their clinical translation. "Exploring the therapeutic potential of perinatal cell SECRETomes - SECRET" sets out with the ambition to train 10 doctoral candidates (DCs) to disentangle the inherent therapeutic potential of perinatal cell secretomes (either as a whole or as fractionated small EVs) in order to possibile translate novel biologics into the clinic. Their specific focus will be the characterisation, the delivery and the preclinical evaluation of these perinatal secretomes as an innovative therapeutic approaches for MI, IS and MS. To achieve this goal, Università Cattolica del Sacro Cuore (Prof. Ornella Parolini, Italy) unites internationally-renowned academic and non-academic institutions from Italy, The Netherlands, Germany, Belgium, Portugal and Switzerland, to deliver an inter-disciplinary programme that goes beyond current state-of-the-art research in next generation medicinal product development and validation. These include the development and use of iPSC-derived organoids and organ-on-a-chip modelsto identify the most efficient perinatal cellsecretome in terms of immunomodulation, angiogenesis, anti-fibrotic, cardio-protective and neuro-trophic properties, as well as the assessment of their in vivo cardiac reparative and neuro-regenerative potential using novel delivery methods.

Funded by the Industrial Research Fund (IOF) of the University of Antwerp (01/09/2024 - 31/08/2025)

Key µNEURO members involved: Prof. Winnok De Vos (Laboratory of Cell Biology and Histology), Prof. Jan Sijbers (Imec - Vision Lab) (& Prof. Regan Watts)

Abstract

Modern cell and developmental biology increasingly rely on 3D cell culture models such as organoids. However, the inability to characterize these specimens at the cellular level with high throughput hampers their integration in an industrial setting. To address this bottleneck, we have developed a module for imaging organoids in flow, based on a transparent agarose fluidic chip that enables efficient and consistent 3D recordings with theoretically unlimited throughput. The chip is cast from a custom-designed 3D-printed mold and is coupled to a mechanically controlled syringe pump to enable fast and precise sample positioning. We have benchmarked the setup on a commercial digitally scanned light sheet microscope using chemically cleared glioblastoma spheroids and found it to deliver consistent image quality at a throughput of 40 completely scanned samples per hour. By design, the fluidic chip offers a cost-effective, accessible, and efficient solution for organoid imaging on essentially any microscope, which makes it an attractive add-on for microscope vendors and users, in particular CROs and core facilities. To protect our IP, we have initiated a priority filing for the method and device design. Within this POC CREATE project, we intend to assess and extend its market potential by focusing on three main aspects: (i) testing compatibility with different commercial light sheet systems and organoid applications; (ii) automating sample positioning and selection; (iii) improving the image quality and speed through adaptive motion correction. This way, we intend to offer a robust and intuitive screening platform for biomedical and pharmaceutical R&D based on physiologically relevant model systems. While perfecting our product, we will investigate whether service, licensing, or direct sales is the preferred business trajectory.

This project is funded by the European Research Council (ERC CoG, 01/05/2024 - 30/04/2029, Grant Agreement Nr. )

The project is hosted by Prof. Jeurissen in Imec-Vision Lab, and partly relies on collaboration with the Bio-Imaging Lab (Prof. Verhoye) and the Laboratory of Cell Biology and Histology (Prof. De Vos).

Abstract

The ability to study tissue microstructure in vivo and completely noninvasively using magnetic resonance imaging (MRI) has the potential to radically change how we detect, monitor, and treat diseases, in particular the many neurodegenerative diseases that affect our world's aging population. Unfortunately, the MRI signal is a very indirect measure of microstructure, and the variety of contributing factors complicates a one-to-one association between the MRI measurements and the biological substrate. As a result, microstructural mapping is still a poorly understood and challenging inverse problem that often yields inconsistent and contradictory outcomes. In ADAMI, I will take the next leap in microstructure imaging by approaching the problem in a completely data-driven fashion as opposed to the state of-the-art that is model-driven. This paradigm shift will enable me to turn the MRI scanner into a powerful in vivo microscope that can provide reliable information about tissue microstructure that closely matches the underlying cellular composition. Through these innovations, ADAMI will advance the field of medical imaging by introducing a groundbreaking data-driven approach to microstructure imaging which will significantly impact the understanding, diagnosis, and monitoring of brain diseases and beyond.

VLAIO Innovation Mandate (01/01/2024 - 31/12/2025) of Dr. Tim Van De Looverbosch (Laboratory of Cell Biology and Histology)

Key µNEURO members involved: Prof. Winnok De Vos (Laboratory of Cell Biology and Histology) and Prof. Jan Sijbers (Imec - Vision Lab)

Abstract

Despite technological improvements, drug discovery programs have become less successful and more expensive over time. This can in part be attributed to the rigid implementation of sub-optimal preclinical screening platforms that mainly use simple cell cultures, and toxicity and pharmacokinetics experiments with animal models. Organoids are the promise of next-generation model systems for preclinical research. The main roadblocks for organoid adoption are their lack of reproducibility and the absence of technology to characterise them in depth. We believe that robust and reproducible organoid production and analysis can only be guaranteed when organoids are characterized in toto with cellular resolution. With this project, we intend to develop a pipeline for fast cellular phenotyping of intact organoids and prepare for launching a spin-off company that offers this as a service platform to the pharma and biotech industry.

FWO Junior Research Project (01/01/2023 - 31/12/2026)

Key µNEURO members involved: Prof. Pieter Van Dyck (MIRA) & Prof. Ben Jeurissen (Imec - Vision Lab)

Abstract

Surgical anterior cruciate ligament (ACL) reconstruction using tendon graft is the standard to treat ACL injuries. However, little is known about the maturation process of human ACL graft and the role of adjacent structural abnormalities herein. There currently exists a high clinical need for improved noninvasive objective measures of ACL graft properties to help inform return to high-demand activities. Next to anatomical magnetic resonance imaging (MRI), quantitative MRI (qMRI) techniques, such as T2* relaxometry and diffusion tensor imaging (DTI), have gained interest for musculoskeletal imaging. qMRI provides objective measures of biophysical tissue properties that allow for monitoring of tissue microstructure. Despite its demonstrated potential to provide biomarkers of ACL graft maturation, standard qMRI suffers from low resolution and long scan times, impeding clinical validation. To improve the trade-off between signal-to-noise ratio, resolution and scan time, we propose a super-resolution reconstruction (SRR) framework for anatomical MRI and qMRI of the knee that will overcome the current limitations for biomarker identification. In this project, we will develop SRR qMRI for T2* relaxometry and DTI of the knee and provide further insight into the condition of maturing ACL graft in patients before return to play. SRR qMRI may also improve our ability to evaluate the effectiveness of additional treatments to accelerate ACL graft maturation.