NEURO RESEARCH GROUP
MSc Students
Alumni
Sinnead Cogill, MSc
Sinnead assessed and characterised metal neurotoxicity and neurodegeneration in key South African mining communities. Optimised an energy-dispersive x-ray approach (the first of its kind in the NRG and the country). The use of N2A-swedish mutated cells activated by Butyric acid revealed that increased exposure to copper and cadmium are of special risk for exacerbating the molecular pathways of neurodegenerative disease.
MSc Students
Tamryn Barron, MSc
Tamryn characterised the localisation of the SARS-CoV-2 Spike and Nucleocapsid proteins in human lung biopsy tissue samples with key autophagy and mitchondrial proteins, through colocalisation analysis and Correlative light electron microscopy. This was the very first application of a colocalisation and CLEM approach to SARS-CoV-2 characterisation. This analysis revealed that the SARS-CoV-2 Spike and Nucleocapsid proteins do interact with critical autophagy and mitochondrial proteins, unveiling an avenue whereby dysfunction is potentially induced in these compartments. An machine learning approach was also taken to automate the detection of the viral particles in electron micrographs and overcome the high error seen in human discernment of these particles. This approach is completely novel in SARS-CoV-2 detection, particularly with molecular identity provided via CLEM.
Samantha Knupp, Honours
Samantha investigated the effects of tubulin disruption on mitochondrial dynamics. Sam also explored the role of autophagy inhibition on mitochondrial dynamics. This was achieved by measuring mitochondrial network, mitochondrial abundance, fission and fusion abundance and autophagosome pool size. By using a tubulin disruptor and inhibiting autophagy using bafilomycin
MSc Students
Fatimah Lakay, Honours
It has been found that the nucleus contains LC3, a protein necessary for autophagy that binds to the autophagosome membrane. The extent of LC3s’ abundance and its’ association with DNA, is unknown. As a result, we carried out a study in which we measured the number of LC3 puncta that are found inside the nucleus in MEF GFP-LC3 cells. In order to demonstrate whether functional autophagy occurs in the nucleus when the lysosomal inhibitor bafilomycin (Baf) is administered, we further evaluated an autophagic receptor, NBR1.
Current students
Sholto De Wet, MSc
PhD student
Sholto is currently looking into the concentration-dependent effects of memantine in neuronal cells and the effect this has on autophagy and mitophagy and the impact this has on cell survival. He has spent a lot of time in the cell culture lab and at the confocal microscope and through collaboration with Dr Rensu Theart, a lecturer at Stellenbosch University’s E&E department, Sholto makes use of a lot of custom made Python and ImageJ pipelines for the purpose of autophagy, mitophagy and mitochondrial micrograph analysis.
Catherine Smit, Honours
MSc student
Aspalathus linearis, also commonly known as rooibos, is an endemic South African plant that is globally gaining popularity for its antioxidant properties and its role as a functional medicinal beverage. However, to what extent the polyphenols within rooibos serve as antioxidants in the neuronal context remains largely unclear. Moreover, it is not known to what extent mitochondrial-derived reactive oxygen species (ROS) is impacted by polyphenols in the face of neuronal dysfunction that is implicated with toxic ROS generation. Therefore, the aim of Catherine's project is to quantitatively assess the impact of both fermented and green rooibos derived polyphenols on mitochondrial-derived ROS in a model of neuronal injury
THE TEAM
Nicola Heathcote, MSc
PhD student
Nicola is looking at the three different autophagy probes which are currently used to assess autophagy activity and flux, and comparing the probes to each other in terms of sensitivity and specificity in different imaging modalities, mainly confocal, SR-SIM and CLEM with the main overarching aim to develop an algorithm which is able to automatically detect and segment autophagosomes in EM micrographs only
Meenal Bhaga, Honours
MSc student
Meenal is investigating the effects of Metformin as a sensitizing agent in order to work adjuvantly with chemotherapy to promote cell death in a 3D spheroid model of Glioblastoma multiforme. Confocal and SEM images of the same sphere will be used. These images will then be overlaid in order to visually see if there are any changes in cell morphology and to visualise molecularly labelled cell death and autophagy markers.
Asandile Mangali, Honours
MSc student
Intensive mining of heavy metals increases exposure and risk for metal-induced neurotoxicity (MIN). MIN can result in neurodegenerative diseases, where mitochondrial dysfunction is centrally implicated. However, the effect of heavy-metal on mitochondrial quality control is unclear. Therefore, Asandile's study aims to assess the effects of MIN on mitophagy and mitochondrial dysfunction using molecular and imaging techniques. Additionally, he is investigating the risk factor of mining communities for developing MIN
Nsuku Nkuna, Honours
MSc student
Nsuku is assessing the role of 5-aminolevulinic acid (5-ALA) and autophagy inhibition on chemotherapy cell death sensitisation. The study aims to determine whether 5-ALA enhances cell death sensitisation when used in combination with the chemotherapy temozolomide (TMZ) and the autophagy inhibitor, chloroquine (CQ). The effects of 5-ALA, in combination with TMZ and CQ, on the mitochondria are assessed. Finally, the extent to which 5-ALA, TMZ and CQ impact autophagy activity was visualised and quantified.
Zenande Nkentsha, Honours
Zenande's study looked at two areas of large interest in the neuroscience field. Firstly, autophagy which is a protein self degradation system and mitochondria which are key organelles in the maintenance of cellular homeostasis. MEF -GFP LC3 cells were subjected to different treatments to modulate autophagy activity. Different functional mitochondrial parameters such as fission and fusion events, mitochondrial number and morphology were analysed of cells in each treatment group. We observed that enhanced autophagy lead to increased mitochondrial activity.
Prof Loos obtained his PhD at Stellenbosch University in 2009. Following a career as Imaging Platform manager, he started the Neuro Research Group in 2011. He has since been working in the fields of cell death, autophagy and neurodegeneration. Prof. Loos strives for innovative and multidisciplinary research of the highest quality and is known to have more enthusiasm and energy than all of his students combined.
Prof Ben Loos, PhD
Principle Investigator
Jurgen Kriel, MSc
PhD
Glioma Treatment and Pathophysiology
Jurgen is investigating the mechanisms involved in autopahgic cell death and whether it can be harnessed as a therapeutic intervention for the treatment of Glioblastoma Multiforme.
Demi Pylman
Honours
Demi is characterizing autophagosomal cargo
Sholto De Wet, MSc
PhD
Probing Autophagic flux
Sholto is investigating the role of autophagosome flux and vesicle dynamics as well as the spatiotemporal distribution of tubulin and mTOR.
Nsuku Nkuna
Honours
Nsuku is characterizing the impact of Ritalin use in autophagy processes
Nicole Heathcote, BScHons
Masters
Modelling Autophagy
Nicola is investigating the impact of autophagy processes on traumatic brain injury and rescue.
Sinnead Cogill
Honours
Sinnead is investigating the physiological dynamics of autophagosomal cargo
Kim Fredericks, BScHons
Masters
Modelling Autophagy
Kim is investigating autophagy modulation as a means for enhancing 5-ALA treatment efficacy in glioma models.
Tamryn Barron
Honours
Tamryn is studying autophagy flux through live cell imaging and computation
Dr André du Toit, PhD
Postdoctoral Fellow
Andre is modelling the autophagy system through the characterization of autophagy flux/activity in neural tissue (in vitro and in vivo) and with machine learning techniques, incorporating computational and systems biology approaches.
Dr Tando Maduna, PhD
Postdoctoral Fellow
Tando is characterizing autophagy and autophagic flux in the developing and the aging nervous system through in vitro and in vivo model systems.
Sholto is investigating the role of autophagosome flux and vesicle dynamics as well as the spatiotemporal distribution of tubulin and mTOR.