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.
Dr. Karisha Roopnarain
Neurology registrar at Tygerberg Hospital
Mmed student at University of Stellenbosch
Research title: Investigation of a novel familial form of Parkinson's disease
Project description: My master's thesis involves the use of whole exome sequencing (WES) in a South African family of Indian ancestry with three generations of Parkinson's disease-affected family members to identify the underlying genetic cause. The three affected members all have clinically confirmed Parkinson's disease. My two supervisors are Professor Jonathan Carr (head of the division of Neurology at Tygerberg Hospital) and Professor Soraya Bardien. Rapidly emerging breakthroughs in genetics in the form of next-generation sequencing, which is increasing being used in neurological diseases and may soon be used in the clinic, requires neurologists and other clinicians treating these patients to be able to interpret and understand these results and counsel the patients appropriately. I am really excited about my project as it gives me the opportunity as a clinician to go into a molecular genetics lab and be trained on the processing and interpretation of the vast number of variants generated by WES, and use this together with the clinical information from the affected individuals to determine the cause. I hope that we will be able to use the results from this study to do further functional studies to determine the effect of the variants identified in the pathophysiological pathways underlying Parkinson's disease on a cellular level.
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.
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 Amokelani Mahungu
Project Title: Development of a custom-designed targeted resequencing gene panel for Parkinson's disease
Currently, studies on the genetic aetiology of Parkinson's disease(PD) are mostly done in European, Asian and North African populations. However, PD is also expected to become a major challenge in Black Sub-Saharan populations as these populations are rapidly aging. It is estimated that there will be approximately 156.7 million individuals above the age of 60 by 2050 in Sub-Saharan African countries (World Population Ageing report 2013). Increased age (above the age of 60 years) is an important risk factor for PD. Previous studies by the Parkinson's Disease Research Group at Stellenbosch University led by Associate Professor Bardien has established that the known PD-causing mutations are not common in Black South African PD patients. My study aims to potentially uncover the genetic aetiology of Parkinson's disease in Black South African populations. This aim will be addressed by establishing a custom-designed multigene next-generation sequencing (NGS) panel for rapid screening of PD genes in local patients. The panel will enable us to screen for novel mutations in the known PD genes as well as for mutations in novel PD genes. Functional studies will also be done to confirm the pathogenicity of the identified mutations. The study will also contribute to the on-going research for improved therapeutic interventions.
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 Caitlin McCaffrey
Project title: Investigating the role of mtDNA in South African patients with Parkinson's disease
Supervisors: Prof Soraya Bardien and Prof David Tabb
Co-supervisor: Ms Amica Muller-Nedebock
This project investigates mitochondrial DNA variation in South African PD patients from mitochondrial sequence data of 58 individuals (29 patients and 29 matched controls). Various publicly available tools to annotate and prioritise the mitochondrial variants are used in the analysis of mitochondrial sequence data. This process of analysis using a myriad of online tools can become tedious and increases the chance of human error. The aim of this project, therefore, is to attempt to automate the annotation and prioritisation mitochondrial variants identified from whole genome sequence data by the production of scripts or plug-ins.
Ms Nicola Du Toit
PAST TEAM MEMBERS
Prof Helena Kuivaniemi
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Dr Annika Neethling
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Ms.Boiketlo Bibi Sebate