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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

UFS welcomes Prof Francis Petersen as new Vice-Chancellor and Rector
2017-04-02

 

Prof Francis Petersen takes up office as the 14th Vice-Chancellor and Rector of the University of the Free State today.
 
“On behalf of the UFS Council and the university community, I would like to welcome Prof Petersen to the university. He brings to the UFS a distinguished academic record, confident leadership, innovative thinking, and an understanding of the extent of the challenges being experienced by universities in the broader South African context,” says Mr Willem Louw, Chairperson of the UFS Council. 
 
“I am excited to join the UFS and look forward to meeting the university community, to get to know the three campuses, and to engage with staff and students. In a way, it was a natural progression for me to be appointed in this position, having been Dean of the Faculty of Engineering and the Built Environment at the University of Cape Town (UCT), and then Deputy Vice-Chancellor: Institutional Innovation at the same university.  On the other hand, I believe that universities in South Africa need strong and innovative leadership. I would like to make a contribution to the higher-education system in this regard.  Moreover, I regard the UFS as a very good university, and see my challenge in taking the UFS to the next level,” says Prof Petersen.
 
“Challenges and making a difference motivate me – whether complex or simplistic, the opportunity to be able to provide solutions and taking people with me while developing these solutions, is what ultimately motivates me.”
 
“It is important that different viewpoints are respected. The UFS must be a place where everyone feels welcome. There must be a strong sense of belonging; staff and students must feel they are making a contribution to the university,” he says.
 
According to Prof Petersen, the major challenge for the university is its institutional climate.  “My focus would be to strive towards creating an institutional climate of inclusivity, respect for one another, valuing diversity in all its forms, and to make the university a welcoming place. The UFS is in the process of developing an Integrated Transformation Plan (ITP) that will serve as the road map to address the institutional climate challenge, but will also assist (if implemented effectively) in excelling the UFS in areas of teaching and learning, research and innovation, and community engagement through scholarship,” says Prof Petersen.

“I am a good listener, I am outcome-based, and my vision for the university includes diversity, inclusivity, and academic excellence,” he says.

Prof Petersen was born in Oudtshoorn and grew up in Malmesbury in the Western Cape, where he also matriculated. He graduated from Stellenbosch University with a BEng (Chem Eng), MEng (Metal Eng), and PhD (Eng) degrees and completed a short course on Financial Skills for Executive Management. He is a recipient of the Ernest Oppenheimer Memorial Trust Award for research excellence, and was visiting professor at the Cape Technikon and extraordinary professor in the Department of Chemical Engineering at Stellenbosch University. He is a regular reviewer of journals, and member of a range of editorial boards for international journals. He is also a registered professional engineer with the Engineering Council of South Africa and a Fellow of both the South African Institute of Mining and Metallurgy, and the South African Academy of Engineers.

 He brings to the position of Vice-Chancellor and Rector his extensive experience of management in both the industry and academic sectors. He has been the executive head of strategy at Anglo American Platinum and head of the Department of Chemical Engineering at the Cape Technikon (now Cape Peninsula University of Technology). Among others, he previously served as member on the Board of the Council of Scientific and Industrial Research, the National Advisory Council on Innovation, and the Council of the Academy of Science of South Africa.

 Prof Petersen is married and has two sons. He was appointed by the UFS Council at the end of 2016 after Prof Jonathan Jansen stepped down as Vice-Chancellor and Rector on 31 August 2016, serving in this position since July 2009. Prof Nicky Morgan, Vice-Rector: Operations at the UFS, has been acting Vice-Chancellor and Rector since 1 September 2016.

 

Released by:
Lacea Loader (Director: Communication and Brand Management)
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