Stellenbosch_University

Division of Molecular Biology and Human Genetics, Stellenbosch University, Cape Town, South Africa & Tygerberg Academic Hospital / Stellenbosch University Faculty of Medicine and Health Sciences

Division of Molecular Biology and Human Genetics, Stellenbosch University, Cape Town, South Africa

Co-Investigator:
Prof Soraya Bardien, PhD

Genetics and preclinical science expertise and facilities:
Our centre is well-equipped to conduct most experiments in molecular genetics and molecular biology. This includes PCR machines, real-time PCR machines, Western blotting equipment and expertise, an epMotion 5070 liquid handling workstation and a dedicated cell culture facility. In addition, we have access to state-of-the-art next-generation sequencing and microscopy facilities through the Central Analytical Facilities, an open access core facility which offers their services as a reduced fee to our university (https://www.sun.ac.za/english/faculty/science/CAF/).

Current research programmes:
One of our current research programs is focussed on the genetic aetiology of Parkinson's disease (PD). We use next-generation sequencing approaches including whole exome sequencing and targeted gene panels to identify pathogenic mutations in known and novel PD genes. We also do functional studies, mainly focussing on mitochondrial assays, to determine the effect of mutations that we identify. To date, we have collected DNA samples of over 1,900 individuals comprising 678 PD probands for our genetic analysis.

Top five publications from the past five years:
Kuipers DJS, Carr J, Bardien S, Thomas P, Sebate B, Breedveld GJ, van Minkelen R, Brouwer RWW, van Ijcken WFJ, van Slegtenhorst MA, Bonifati V, Quadri M. PTRHD1 Loss-of-function mutation in an African family with juvenile-onset Parkinsonism and intellectual disability. Mov Disord. 2018; 33(11): 1814-1819. doi: 10.1002/mds.27501 PubMed PMID: 30398675

Neethling A, Engelbrecht L, Loos B, Kinnear C, Theart R, Abrahams S, Niesler T, Mellick GD, Williams M, Bardien S. Wild-type and mutant (G2019S) leucine-rich repeat kinase 2 (LRRK2) associate with subunits of the translocase of outer mitochondrial membrane (TOM) complex. Exp Cell Res. 2018. pii: S0014-4827(18)31186-8. doi: 10.1016/j.yexcr.2018.12.022. [Epub ahead of print] PubMed PMID: 30597143.

van der Merwe C, van Dyk HC, Engelbrecht L, van der Westhuizen FH, Kinnear C, Loos B, Bardien S. Curcumin rescues a PINK1 knock down SH-SY5Y cellular model of Parkinson's disease from mitochondrial dysfunction and cell death. Mol Neurobiol. 2017;54(4):2752-2762. doi: 10.1007/s12035-016-9843-0

Choudhury A, Ramsay M, Hazelhurst S, Aron S, Bardien S, Botha G, Chimusa ER, Christoffels A, Gamieldien J, Sefid-Dashti MJ, Joubert F, Meintjes A, Mulder N, Ramesar R, Rees J, Scholtz K, Sengupta D, Soodyall H, Venter P, Warnich L, Pepper MS. Whole-genome sequencing for an enhanced understanding of genetic variation among South Africans. Nat Commun. 2017;8(1):2062. doi:10.1038/s41467-017-00663-9.

van der Merwe C, Jalali Sefid Dashti Z, Christoffels A, Loos B, Bardien S. Evidence for a common biological pathway linking three PD-causing genes: parkin, PINK1 and DJ-1. Eur J Neurosci. 2015;41(9):1113-1125. doi: 10.1111/ejn.12872.

How the new international centre benefit research and clinical programmes:
Being part of this international collaboration will raise awareness of our research and expose our group to world-class facilities and expertise. Also, the training of registrars in both clinical and genetic investigations of neuromuscular conditions is a significant advantage as registrars would not usually gain this type of expertise in South Africa. Finally, being part of this centre will allow us leverage additional grant funding from other local and international sources. 

Tygerberg Academic Hospital / Stellenbosch University Faculty of Medicine and Health Sciences

Co-Investigator:
Dr Franclo Henning; MBChB; FC Neurol (SA); PhD Consultant Neurologist, Division of Neurology

Clinical neuromuscular expertise, patients and geographical region:
Our areas of expertise are motor neuron disease, inflammatory myopathies and inherited myopathies. We provide a full neuromuscular service, including neurophysiology and muscle/nerve biopsies. We serve a geographical area of approximately 130 000 km2 and a population of 6 million. Our neuromuscular clinic receives approximately 1100 patient visits per year (of which approximately 10-15% are new patients), while our neurophysiology clinic receives approximately 500-600 visits per year. We also provide a dedicated multidisciplinary motor neuron disease clinic, as well as a neurogenetics service including clinical geneticists and genetic counselling.

Genetics, preclinical science expertise and facilities: We have a genetics research laboratory on site, with expertise in neurodegenerative disorders. Other preclinical science expertise includes single muscle fibre contractility studies.

Current research programmes: Ongoing research includes epidemiology and genetics of MND in South Africa, ethnic variability in MND presentation and clinical course, building community based MND caregiver interventions in South Africa (collaborative research funded by the ALS Association), and single fibre contractility studies in inflammatory myopathies.

Top three publications from the past five years: Henning F, Cunninghame CA, Martin MA, Rubio JA, Arenas J, Lucia A, Hernández-Lain A, Kohn TA. Muscle fiber type proportion and size is not altered in McArdle disease. Muscle Nerve. 2017 Jun;55(6):916-918.

Van Hillegondsberg L, Carr J, Brey N, Henning F. Using Eulerian video magnification to enhance detection of fasciculations in people with amyotrophic lateral sclerosis. Muscle Nerve. 2017 Dec;56(6):1063-1067.

Clinical features and prognosis of amyotrophic lateral sclerosis in Africa: the TROPALS study. Luna J, Diagana M, Ait Aissa L, Tazir M, Ali Pacha L, Kacem I, Gouider R, Henning F, Basse A, Cisse O, Balogou AAK, Kombate D, Agbetou M, Houinato D, Millogo A, Agba T, Belo M, Penoty M, Raymondeau-Moustafa M, Hamidou B, Couratier P, Preux PM, Marin B; TROPALS Collaboration. J Neurol Neurosurg Psychiatry. 2018 Sep 21.

How the new international centre will benefit research and clinical programmes: There is an unmet need for molecular diagnostic services for patients with inherited neuromuscular disorders in South Africa. This collaborative project will enable us to deeply phenotype and genotype the spectrum of neuromuscular disorders in South Africa, and allow us to identify novel mutations and phenotypes among the different population groups of South Africa. This will enable us to build local expertise and capacity in order to provide a better service to our patients with inherited neuromuscular disorders.