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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

Prof Jonathan Jansen bids farewell to Kovsies
2016-08-31

 

Dear Kovsie staff and students

This is my final message to you all.

I wish to use this opportunity for some brief reflections, share a word of gratitude, and convey a sense of the future for our beloved university.

Since the announcement of my departure, I have had more than a dozen breakfasts with mainly students, but also staff, to offer an opportunity for the final sharing of thoughts and, of course, goodbyes. The most common questions asked at those breakfast sessions were the following, with my responses. I repeat them here, since these might also be of interest or concern to you.

What are your proudest achievements?
Two things. The increase in the academic standard for the UFS, both in terms of admission standards and pass rates, but also in relation to the requirements for appointment and promotion especially of professors. This is important because in a globally competitive world, a university stands or falls by the quality of its degrees. And for this you need the best students and the best professors.

What would you do differently, given another chance?
Nothing. I believe that leadership is about doing the best you can with the cards you are dealt in the circumstances in which you are placed. There is no point in second-guessing past decisions. I have always been ambitious as a leader, knowing that most of my goals would be met, and that some would not. That is normal in large and complex organisations, and so, I do not sit around pondering regrets, only remembering with gratitude the things we could achieve together.

What did you learn?
A lot. I learnt that our students have tremendous capacity for greatness both in their academic pursuits but also in their ability to live, and learn, and love together. I have learnt never to underestimate the capacity of our youth to excel in whatever they do. Sometimes I felt I was more ambitious for our students and staff, than they were for themselves. But I have constantly been surprised by the capacity of young students to rise above bitterness and division, and to make great our campus, country, and continent.

I learnt, again, that the overwhelming majority of our staff and students are good people, respectful of each other, and determined to work together to heal our broken past and build a more just society. And I learnt that it is much more fulfilling to build up than to break down, to embrace than to exclude, and to love than to hate.

Were you frustrated with the pace of transformation?
Sometimes, yes. But fortunately I studied educational organisations all my life, mainly schools and universities. Universities are called institutions for a reason, and on century-old sites like the historic Bloemfontein Campus of the University of the Free State, there are core beliefs, values, and practices deeply ingrained in the culture of the place.

Anyone, therefore, who believes that transformation is easy, has obviously never tried to change an old university. It is difficult. You will get blowback. You will get bad press. You will, sadly, lose the support of some people. Some believe the university is changing too fast while others will tell you it is not changing fast enough. As you press for change, you find the university going two steps forward and one step back; in these circumstances, the solemn duty of the leader is simply to ensure that the overall momentum is always forward.

For such a time as this –
a commemorative journey:
2009-2016 (PDF book)

Description: Prof Jansen commemorative journey2 Tags: Prof Jansen commemorative journey

I therefore budget for disappointment even as I relish the many changes we have experienced together over the past seven years. If you want to obtain an objective sense of the scale of the changes at the UFS, ask those students and staff who were here in 2009, not those who came recently. They will tell you that we have a very different university, even though we all acknowledge that there is still some distance to travel. Our remarkable story of change is told in the recent Transformation Audit of the UFS, chaired by Prof Barney Pityana; that Audit Report will be released after it is read and studied by the University Council at its November meeting.

At an individual level, I learnt that most campus citizens change quickly and others more slowly, and that one has a duty to constantly push for change, but also to be patient about change. And I learnt that the ideal change retains the best of our past even as we embrace a more just and inclusive future in which all campus citizens feel that the university truly belongs to each and every one of them.

Are you optimistic about the future of our university?

Yes. The UFS is a very well-managed university thanks to the exceptional talent in the management of our finances, human resources and information technology environments. By the end of 2016, we will have record enrolments, from undergraduates to doctoral students, which is good for our future income. We run a tight ship with regard to the university’s finances, and we have greatly improved the academic standard of our qualifications; in this regard, I am very proud of my senior management team, and the talented middle management personnel, and those who make things work at the coalface of our operations.

I am very concerned, however, about future funding of the 26 public universities and the extremely vulnerable situation of at least 10 higher-education institutions. The economy is not growing and the costs of running a modern university are escalating. The delays in government commission reports on tuition fees do not help, and there seems no urgency ‘higher up’ to make the tough decisions.

We have to ensure free education for the poorest students — that is the position of your senior management – but we also need to guarantee the financial sustainability of our universities. The task of the UFS leadership, in this period of uncertainty, is to manage those two expectations as best we can. But this cannot happen without your assistance, and I do ask that you provide the new Rector and his or her team with the same understanding and support which I have enjoyed from you.

In conclusion
I am grateful.

To the many hundreds of students who have passed through my office and our home, and who sat in my many lectures and engaged me in your residences – thank you for enriching my sense of life and leadership. I am grateful that Grace and I could support and mentor many of you over the years and see you graduate. I am a better leader because of you.

To the staff of the three campuses – there is no university Rector, I can assure you, who enjoyed more love and support than what you offered me since the day I arrived here. Students come and go, but you have been my foundation year after year, and I thank you for that.

To parents, friends, and followers off-campus, in South Africa and abroad – thank you for hundreds of letters, emails, phone calls, prayers and ‘packages of support’ (from biltong to books). In the most difficult times, you rallied from everywhere with a word of support, often on social media. Know this: your words kept me calm in the storm.

Thank you, everyone.

Goodbye.

Prof Jonathan Jansen
Vice-Chancellor and Rector
University of the Free State

Description: Prof Jansen saying goodbey Tags: Prof Jansen saying goodbey

Prof Jonathan Jansen steps down as UFS Vice-Chancellor and Rector (16 May 2016)

 

 


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