Prof Soraya Bardien
Soraya Bardien has a PhD in human genetics and has more than 15 years of experience with working on the genetic causes of various disorders. During her PhD she received training at the Baylor College of Medicine in Houston, USA, the University of Texas Southwestern Medical Center in Dallas, USA and the Institute of Ophthalmology in London, UK. She completed postdoctoral fellowships at various institutions in South Africa and is currently appointed as an Associate Professor at Stellenbosch University.
Prof Jonathan Carr
Prof. Jonathan Carr is a neurologist at Tygerberg Hospital and Stellenbosch University. He is currently working on a number of areas including stigma and attitudes of traditional healers towards Parkinson disease in the Xhosa population, and imaging of functional tremor with FDG-PET. Important collaborations include those with the University of Groningen regarding FDG-PET analysis of Parkinsonian subtypes and the International Parkinson and Movement Disorder Society (MDS) on methodology for video uploads from remote areas.
Dr Shameemah Abrahams
Research Title: The investigation of the possible therapeutic effect of curcumin on mitochondrial dysfunction in Parkinson's disease
Project Description: The mechanisms underlying Parkinson's disease pathogenesis is as yet unknown, however, some theories exist including oxidative stress and mitochondrial dysfunction. To date, no cure is available for Parkinson's disease and the current therapy strategies including drugs such as levodopa, carbidopa and amantadine, target the alleviation of symptoms and have no effect on the underlying pathogenesis or reduction of neuronal loss. This highlights the need to gain a better understanding of Parkinson's disease pathogenesis and thereby develop therapies targeted at the underlying mechanisms in order to ultimately reduce or prevent neuronal loss. The overall aim of this project is to investigate the potential therapeutic effects of curcumin on mitochondrial dysfunction using Parkinson's disease patient-derived fibroblast cells.
Project Title: Investigating mtDNA Variation in South African Parkinson's Disease (PD) Patients
Project description: Multiple lines of evidence support a role of mtDNA involvement in PD pathogenesis, yet the association between mtDNA and PD remains controversial. Furthermore, previous studies investigating mtDNA involvement in PD have primarily been centred around European populations and reports on African mtDNA variation and PD are severely lacking. Consequently, this study aims to investigate whether mtDNA variation plays a significant role in the development of PD in South African patients, by means of high-throughput, next generation sequencing (NGS).
Ms Katelyn Cuttler
Project Title: Investigation of neurexin 2 as a candidate for Parkinson's disease
Project Description: A recent MSc study (B. Sebate) on a South African Afrikaner family with members diagnosed with autosomal dominant Parkinson's disease (PD) identified a novel putative pathogenic mutation in neurexin 2 (NRXN2). This protein is associated with pathways related to calcium channel regulation, transmembrane signalling receptor activity, neuronal cell adhesion, synaptic organization and neuroligin family protein binding at the synapse. It is also highly expressed in the substantia nigra, which is the main region of the brain affected by PD. Thus, this was the first study to implicate
NRXN2 in PD. Therefore, the aim of the present project is to determine if
NRXN2 is a candidate gene for PD by utilizing functional studies
Ms Nikita Pillay
Project Title: Whole Exome Sequencing Approaches for Novel Gene Discovery in South African Parkinson's Disease Families
Project Description: Genetic research into South African families has shown little causative correlation to the established Parkinson's Disease (PD) genes indicating that these PD patients may harbour novel causative genes. The advent of next generation sequencing (NGS) has made it possible for the identification of rare, highly penetrant variants in multi-incident family pedigrees. My study aims to develop and implement effective bioinformatic methods of NGS analysis to identify the pathogenic mutations underlying PD in South African multiplex families. This could provide insight into the 'missing heritability' of PD in underrepresented ethnic groups.
Ms Maryam Hassan
MSc student at the University of the Western Cape. Main supervisor (Dr. Ruben Cloete) and co-supervisor A/Prof. Soraya Bardien
Project title: In
silico and experimental prioritization of sequence variants identified in a South African family with Parkinson's disease
My project will build on the findings from Dr. Karisha Roopnarain's MMed project.
During Karisha's project, eleven candidate genes were prioritised after whole exome sequencing was performed on affected family members from a multiplex South African family. Further investigation is needed to elucidate their possible role in PD pathogenesis. Various computational methods including molecular dynamic simulation studies will be used to hypothesize which mutation in the prioritized genes adversely affects the stability, structure and function of the respective proteins. One candidate gene will then be selected for wet-lab functional studies. The findings of the study have the potential to provide novel insights into the mechanisms underlying PD which may ultimately pave the way to personalized treatment that could prevent the onset or progression of this debilitating disorder.
Ms Sinead Robberts
Project Title: Validating DNA variants detected by massively parallel sequencing of a neurological research gene panel for a South African person with Parkinson's disease
Project description: To investigate and assess the genetic variants that were identified in a single DNA sample. This sample was used as control DNA during the course of a next generation sequencing project, which aimed to identify the genetic determinants of Parkinson's disease in an African cohort. I will focus primarily on technical errors found within the control sample dataset. These technical errors may introduce difficulty in identifying true pathogenic variants. Considering these errors provide aid when implementing variant prioritization methods.
Ms Minke Bekker
Project Title: Investigating the neuroprotective properties of curcumin through monitoring autophagy in a SH-SY5Y cell line.
Autophagy is a cellular response to nutrient deprivation and functions to promote cell survival through the catabolism of cellular components. Through the degradation of misfolded or accumulated proteins, autophagy also exhibits a cytoprotective role. Excessive or dysregulated autophagy, however, induces apoptosis. A delicate balance therefore exists between the induction of either cell survival and cell death via the autophagic pathway. The aim of this study is to assess the mechanisms of autophagy induced by curcumin and paraquat models, subsequently investigating the potential of curcumin to attenuate apoptosis via autophagy.
Ms Devina Chetty
Project title: Evaluation of the Neuroprotective Effect of Curcumin on an
In Vitro Dopamine Toxicity Model of Parkinson's Disease
Project description: Significant scientific advances have prompted the mass production of synthetic drugs to treat diseases that threaten human health. However, due to the side effects and limited efficacy of these drugs, there is a call to pursue natural compounds for our medicinal needs. Parkinson's disease (PD) is an age-related motor disorder of the central nervous system that is the second most common neurological disease worldwide. PD is characterized by the mass degeneration of dopamine-producing neurons in the substantia nigra pars compacta, and the formation of Lewy bodies (protein aggregates). Existing PD drugs do not halt disease progression and are generally associated with long term side effects, and reduced efficacy over time. Curcumin has been shown to protect against many molecular events that may lead to neurodegeneration in PD, including oxidative stress. The aim of this study is to create a dopamine toxicity model of cultured SH-SY5Y cells which will be used to investigate the effects of curcumin on various cellular features such as cell viability and morphology. It is hypothesized that overexpression of mutant
PINK1 (associated with familial PD) will produce a cellular model of dopamine and toxic quinone accumulation, leading to neurotoxicity which will be significantly rescued by curcumin via the reduction of oxidative stress and regulation of dopamine metabolism. The investigation of the effectiveness of this powerful antioxidant in cellular models may lead to more effective treatments for PD.
Ms Zuné Jansen van Rensburg
PAST TEAM MEMBERS
Dr Annika Neethling
Ms Thea Heinemeyer
Mrs Monique Stemmet
Ms.Boiketlo Bibi Sebate
Dr. Karisha Roopnarain
Ms Amokelani Mahungu
Ms Caitlin McCaffrey
Ms Nicola Du Toit