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20 September 2024 | Story André Damons | Photo Supplied
zebrafish-blue-in-aquarium
Zebrafish blue in an aquarium.

A researcher from the University of the Free State (UFS) hopes to make living with epilepsy and other diseases of the central nervous system (CNS) easier by using South African plants extracts which may have anti-epileptic properties and testing them on zebrafish larvae.

Prof Anke Wilhelm, Associate Professor and Divisional Head of Organic Chemistry in the UFS Department of Chemistry, focuses her research on the isolation of active GABAergic compounds (substances that affect the brain’s GABA system, which helps control nervous system activity) by using a test that measures the movement of zebrafish larvae.

Even though obtaining regulatory approval for use as a treatment for epilepsy is a long and complex process, Prof Wilhelm hopes to contribute to the better pain management of people suffering from epilepsy and diseases of the CNS through an affordable alternative drug with less side effects.

The tests are done in a zebrafish bioassay (an analytical method to determine the potency of a substance by its effect on living animals) housed at the UFS’ Chemistry Department.

Why zebrafish larvae?

Prof Wilhelm, who is a National Research Foundation Y2-rated synthetic organic chemist, says zebrafish share about 70% of their genes with humans, and about 84% of human genes known to be associated with diseases have a counterpart in zebrafish. This makes them a valuable model for studying human biology and disease.

“Zebrafish are powerful tools for modelling a wide range of CNS diseases, contributing significantly to the understanding of disease mechanisms and the development of potential treatments,” she says. “Mood disorders, anxiety, insomnia, and attention deficit hyperactivity disorder (ADHD) are all diseases which may be studied through this bioassay.”

She explains that the zebrafish larvae are studied seven days after fertilisation in their bioassay. The larvae are incubated with the specific plant extract at a certain (non-toxic) concentration for three hours. Pentylenetetrazol (PTZ), a GABAA receptor antagonist that has been extensively used in rodent models for acute seizure and anxiety, is then administered to induce concentration-dependent seizures in the zebrafish larvae.

“GABA receptor antagonists are drugs that inhibit the action of gamma-aminobutyric acid, the chief inhibitory neurotransmitter in the mammalian central nervous system,” Prof Wilhelm says. “A specialised infrared camera is then used to track the movement of the larvae inside a chamber. The data is then converted into a graph which shows the movement of each larva over 30 minutes.

“If lowering of movement is observed at a specific concentration it means that the plant extract may have the potential to be used as an epileptic drug, since it has the ability to counteract the induced seizure in the larvae. This bioassay is extremely useful in drug discovery and toxicity screening of plant extracts.”

Zebrafish embryos, she says, develop quickly, with major organs forming within 36 hours of fertilisation. This rapid development allows researchers to observe the effects of experiments in a short period. The maintenance of a zebrafish model is less costly and labour-intensive than using a rodent model. “The use of zebrafish larvae allows for high-throughput screening due to their small size and transparency, which facilitates observation of CNS-related effects. Their genetic and physiological similarities to humans make them a valuable model for early-stage drug discovery.”

Potential uses

The next step in the research, according to Prof Wilhelm, is to identify a single compound from a natural source which may have potential anti-epileptic activity while causing less side effects than current drugs on the market. Researchers would then investigate the possibility of synthesising such a compound on a large scale, to eliminate the use of a natural resource and promote sustainability.

“Many plant extracts which I have screened show a synergistic effect in the zebrafish bioassay, meaning that the extract or the combination of compounds shows potential, but the isolated compounds are inactive. Even if a plant extract shows promise in preclinical and early clinical studies, obtaining regulatory approval for use as a treatment for epilepsy is a long and complex process.

“This includes demonstrating consistent efficacy, safety, and quality in large-scale clinical trials. One of the major challenges in using plant extracts is the lack of standardisation. The concentration of active compounds in plant extracts can vary depending on factors like the plant's growing conditions, harvest time, and extraction methods. This variability makes it difficult to ensure consistent efficacy and safety, therefore this is a time-consuming process.”

Green chemistry

After being approached by Dr Glen Taylor, Senior Director of the UFS Directorate Research Development (DRD), in 2017, regarding funding for Noldus Daniovision equipment, Prof Wilhelm received training from Prof Matthias Hamburger of the University of Basel in Switzerland on how to use such equipment. The larval zebrafish locomotive bioassay was established at the UFS Chemistry Department during 2017 and 2018 and now provides a third-stream income for the department, in conjunction with the Department of Genetics, where the adult zebrafish are housed.

Prof Wilhelm’s other research interests include green chemistry, food sustainability, and recycling. She is looking into green extraction techniques using non-conventional extraction methods to recover valuable bioactive compounds from agricultural and food residues. “Techniques like ultrasound, microwave-assisted extraction, and the use of deep eutectic solvents are becoming popular for their efficiency and alignment with circular economy principles.”

News Archive

During 2011: Prestige Scholars Programme (PSP)
2011-12-01

The University has designed the Vice-Chancellor’s Prestige Scholars Programme (PSP) to promote and support the intellectual breadth and depth required of young scholars to pose questions and generate knowledge in their disciplines and hence to occupy the vanguards of contemporary intellectual enquiry. The programme specifically targets members of the academic staff who are near completion, or have newly completed, their doctoral studies.

The goal is to select no more than 100 of the most promising young scholars and to make substantial investments in their development towards becoming full professors. A tailored, intensive programme of support is designated that combines international placement working alongside leading scholars in the discipline of the prestige scholar, with intensive mentorship and support from within the university.

 Description: 2011 PSP_Thuthuka  Tags: 2011 PSP_Thuthuka

Elite young scholars on the Vice-Chancellor’s Prestige Scholars Programme generated R1,2 million in National Research Foundation Thuthuka and Blue Skies funding in 2011 alone. Dr Katinka de Wet in the Department of Sociology was awarded Blue Skies funding for her work on the Hybrid Identity of the HIV/Aids patient. Thuthuka Grant holders Drs Cilliers van den Berg, Olihile Sebolai, Dirk Opperman and Diaan van der Westhuizen work in the fields of German and Afrikaans trauma literature, microbiology, structural and evolutionary biology, and architecture, respectively. This broad disciplinary range typifies the depth and extraordinary range of scholarship present among junior academics at the UFS.


 Description: 2011 PSP_Liza Coetsee Tags: 2011 PSP_Liza Coetsee

Dr Liza Coetsee, a Y2-rated physicist, is the first of the Vice-Chancellor’s elite cohort of Prestige Scholars to submit for National Research Foundation rating. Dr Coetsee works on the latest of the Nanotechnology Surface Science systems housed in our Department of Physics. As Prestige Scholar, Dr Coetsee conducts research on phosphor solar cells. Her aim is to establish a new Phosphor Solar Cell field at the University of the Free State with Proff. Hendrik Swart and Koos Terblans. As a member of the Prestige Scholar Programme, Dr Coetsee will work in collaboration both with colleagues from the Nelson Mandela Metropolitan University and Prof. Eray Aydil from the University of Minnesota and Editor-in-Chief of the Journal of Vacuum Science & Technology.


 Description: 2011 PSP_Olihile Sebolai Tags: 2011 PSP_Olihile Sebolai

Dr Olihile Sebolai is one of the 2 Vice-Chancellor’s elite Prestige Scholars and a microbiologist. In 2011, Dr Sebolai was awarded a Thuthuka Grant for his research on the yeast pathogen Cryptococcus neoformans, the cause of life-threatening Aids-defining illnesses such as meningitis. Dr Sebolai considers how cryptococcal lipids mediate infectious processes leading to illness. An understanding of these cellular processes will offer hope for future drug development to combat the scourge of cryptococcal meningitis, annually causing the death of over half a million people in Sub-Saharan Africa. Dr Sebolai is also interested in mapping the prevalence and distribution pattern of cryptococcal meningitis in the Free State. This, in turn, will assist health authorities to manage current infections and plan appropriately for potential outbreaks. The Prestige Scholars Programme, with the assistance of the National Research Foundation, will afford Dr Sebolai the opportunity to pursue his research in laboratories in the United States and India in 2012 and 2013.


 Description: 2011 PSP_Louis Holtzhausen Tags: 2011 PSP_Louis Holtzhausen

Dr Louis Holtzhausen, member of the Vice-Chancellor’s Prestige Scholars Programme, has been named by the South African Sports Confederation and Olympic Committee (SASCOC) as team doctor for Team South Africa during the All Africa Games, the largest sports event in Africa. National teams from African countries participated in 23 sports events. As an esteemed South African academic in sports medicine Dr Holtzhausens’ participation was an extension of the work already being done under his supervision at the UFS’s Sports Performance Unit. Many of the athletes who prepared at the Unit were also part of the team. Elite athletes’ illness and injury profiles are one of Dr Holtzhausens’ research focus areas. The exposure to this group in competition was of great value in the identification and development of research niche areas.


 Description: 2011 PSP_ Chantel Swart Tags: 2011 PSP_ Chantel Swart

The South African Society for Microbiology awarded Dr Chantel Swart-Pistor, a Prestige Scholar on the Vice-Chancellor’s elite programme, the top prize for her PhD during a recent gala dinner in Cape Town. Dr Swart-Pistor accomplished a breakthrough in the field of nanotechnology with The influence of mitochondrial inhibitors on zoospore and ascospore development. Her supervisor, Prof. Lodewyk Kock and co-supervisors, Dr Carolina Pohl and Prof. Pieter van Wyk, also stressed the important collaboration with Proff. Hendrik Swart (Physics) and Pieter van Wyk (Centre for Microscopy), which made Dr Swart-Pistor’s work possible. She has presented her work in Beijing (Medichem 2011) and Philadelphia (Biotechnology-2011). She has been invited to return to China in 2012.


 Description: 2011 PSP_ Lizette Erasmus Tags: 2011 PSP_ Lizette Erasmus

Dr Lizette Erasmus, scientific chemist and one of the Vice-Chancellor’s Prestige Scholars, has just returned from a three-month-long research visit to Prof. Hans Niemantsverdriet at the Technical University of Eindhoven in The Netherlands and the University of California, Davis. Dr Erasmus specialises in heterogeneous catalysis. Her visit to Prof. Niemantsverdriet, one of the global experts in the field of surface science, served to round of existing research. In California, Dr Erasmus visited her mentor, Prof. Bruce C. Gates, as part of the objectives of the Rector’s programme for the internationalisation of young researchers. Prof. Gates, an expert in catalysis, could contribute to Dr Erasmus’ research on the characterisation of heterogeneous catalysis and catalytic reactions. In exchange, her expertise in organometallic synthesis added value to Prof. Gates’ existing research. Their continued collaboration gave availed them of the opportunity for interdisciplinary interaction between engineering (Prof. Gates’ speciality) and chemistry, and promises to contribute to increased collaboration between the two universities in future.


 Description: 2011 PSP_Dirk Opperman Tags: 2011 PSP_Dirk Opperman

Dr Dirk Opperman, specialist in structural and evolutionary biology and National Research Foundation Thuthuka Grant holder, joined the Vice-Chancellor’s Prestige Scholars Programme after his postdoctoral work at the Max Planck Institute (KOFO) in Germany. Dr Opperman is the recipient of institutional seed funding to establish a protein crystallisation unit, which in turn led to the donation in 2011 of a multi-million Rand X-ray diffractometer¬ from the University of the Western Cape to complement his existing access to international synchrotrons. Dr Opperman is spending part of 2011 at the University of Exeter (UK) to further his research into the three-dimensional structures of specific enzymes and their trajectories of evolution to specific functions.


 Description: 2011 PSP_Abiodun Ogundeji Tags: 2011 PSP_Abiodun Ogundeji

Abiodun Ogundeji is a member of the Vice-Chancellor's Prestige Scholars Programme. Abiodun's work was recently recognised when he and his co-authors received an award for the best contributed paper at the 49th annual conference of the Agricultural Economics Association of South Africa on the topic, Impact of climate change on planning and dealing with flood disasters in South Africa: A case study of Soweto on Sea. The paper was co-authored by Prof. Giel Viljoen from our Department of Agricultural Economics and Herman Booysen, as well as Gawie du T. de Villiers, Research Associates in the Department of Geography. Abiodun is currently conducting invaluable research on the quantification of the economic value of climate change impacts and the benefits and costs of adaptation in South Africa.

 

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