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 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 Kathryn Step
Project title: Analysis of genetic data-sets to study Parkinson’s disease in a South African study collection
Project description: The present project consists of two aims. The first aim is to use the raw data generated from an international collaborative project (the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson’s Disease (Courage-PD)) in which we participated to identify disease-associated variants. The second aim is to collate all previous South African PD genetic data generated to determine if the variants are consistently shown across the different screening techniques completed in previous studies and to identify pathogenic variants that may have been missed in previous analyses. There are various bioinformatic algorithms that will be used to analyse the data throughout the research project.
Ms Zuné Jansen van Rensburg
PAST TEAM MEMBERS
Prof Helena Kuivaniemi
Mr Oluwafemi Gabriel Oluwole
Sister Debbie Acker
Dr William Haylett
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
Ms Minke Bekker
Ms Sinead Robberts