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20 September 2024 | Story André Damons | Photo Supplied
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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

Position statement: Recent reporting in newspapers
2014-10-03

 

You may have read reports in two Afrikaans newspapers, regarding recent events at the University of the Free State (UFS). Sadly, those reports are inaccurate, one-sided, exaggerated and based not on facts, but on rumour, gossip and unusually personal attacks on members of the university management.

Anyone who spends 10 minutes on our Bloemfontein Campus would wonder what the so-called ‘crisis’ is about.

We are left with no choice other than to consider legal action, as well as the intervention of the South African Press Ombudsman, among other steps, to protect the good name of the institution and the reputation of its staff. No journalist has the right to launch personal and damaging attacks on a university and its personnel, whatever his or her motives, without being fair and factual. In this respect, the newspapers have a case to answer.

But here are the facts in relation to the reports:

  1. No staff member, whether junior or senior, is ever suspended without hard evidence in hand. Such actions are rare, and when done, are preceded by careful reviews of our Human Resource Policies, labour legislation and both internal and external legal advice. Then, and only then, is a suspension affected. A suspension, moreover, does not mean you are guilty and is a precautionary action to allow for the disciplinary investigation and process to be conducted, especially where there is a serious case to answer.
  2. At no stage was the Registrar instructed to leave the university; this is patently false and yet reported as fact. We specifically responded to the media that the Registrar does outstanding work for the university and that it is our intention for him to remain as our Registrar through the end of his contract in 2016.
  3. The Rector does not make decisions by himself. Senior persons, from the position of Dean, upwards, are appointed by statutory and other senior committees of the university and finally approved by Council. No rector can override the decision of a senior committee, and this has not happened at the UFS even in cases where the Rector serves as Chair of that committee. The impression of heavy-handed management at the top insults all our committee structures, including the Institutional Forum – the widest and most inclusive of stakeholder bodies at a university – which reports directly to Council on fairness and compliance of selection processes.
  4. In the case of senior appointments, Council makes the final decision. Council fully supports the actions taken on senior appointments, including a recent senior suspension. The fact that one Council member resigns just before the end of his term, whatever the real reason for this action, does not deter from the fact that the full Council in its last sitting approved the major staffing decisions brought before it. The image therefore that the two newspapers try to create of great turmoil and distress at the university, is completely unfounded.

Even if we wanted to, the university obviously cannot provide details about staffing decisions, especially disciplinary actions in process, since the rights of individuals should be protected in terms of the Human Resource Policies and procedures of the UFS. But that does not give any newspaper the right to speculate or state as fact that which is based on rumour or gossip, or to slander senior personnel of the university. For these reasons, we have been forced to seek legal remedy and correction as a matter of urgency.

Make no mistake, underlying much of the criticism of the university has been a distress about transformation at the UFS; in particular, the perception is created that white colleagues are losing their jobs. The evidence points in the opposite direction. Our progress with equity has been slow and we lag far behind most of the former white universities; that is a fact. More than 90% of our professors are white; most of our senior appointments at professorial level and as heads of department are still overwhelmingly white. Reasonable South Africans would agree that our transformation still has a long way to go and only the mean-spirited would contend otherwise. But based on the two Afrikaans newspaper reports, an impression is left of the aggressive rooting out of white colleagues.

In the past few years the academic standard of the university has significantly improved. We now have the highest academic pass rates in years, in part because we raised the academic standards for admission four years ago. We now have the highest rate of research publications, and among the highest national publication rate of scholarly books, in the history of the UFS. We have one of the most stable financial situations of any university in South Africa, with a strong balance sheet and growing financial reserves way beyond what we had before. We now attract top professors from around the country and other parts of the world, and we have the highest number of rated researchers, through the National Research Foundation, than ever before. And after the constant turmoil of a number of years ago, we now have one of the most stable campuses in South Africa. Those are the facts.

The UFS is also regarded around the world as a university that has become a model of transformation and reconciliation in the student body. The elections of our Student Representative Council are only the most visible example of how far we have come in our leadership diversity. Not a week goes by in which other universities, nationally and abroad, do not come to Kovsies to consult with us on how they can learn from us and deepen their own transformations, especially among students.

Rather than focus on what more than one senior journalist, in reference to the article in Rapport of 21 September 2014, rightly called ‘a hatchet job’ on persons and the university, here are the objective findings of a recent survey of UFS stakeholders: 92% endorse our values; 77% agree with our transformation; 78% believe we are inclusive; and 78% applaud our overall reputation index.  Those are very different numbers from a few years ago when the institution was in crisis.

This is our commitment to all our stakeholders: we will continue our model of inclusive transformation which provides opportunities for study and for employment for all South Africans, including international students and colleagues. We remain committed to our parallel-medium instruction in which Afrikaans remains a language of instruction; we are in fact the only medical school in the country that offers dual education and training in both Afrikaans and English for our students - not only English. We provide bursaries and overseas study opportunities to all our students, irrespective of race. And our ‘future professors’ programme is richly diverse as we seek the academic stars of the future.

We are not perfect as a university management or community. Where we make mistakes, we acknowledge them and try to do better the next time round. But we remain steadfast in our goal of making the UFS a top world university in its academic ambitions and its human commitments.

END

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