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11 July 2024 | Story André Damons | Photo supplied
From top (left to right): Dr Angélique Lewies (researcher from the Robert WM Frater Cardiovascular Research Centre within the UFS Department of Cardiothoracic Surgery), Zurika Murray (behavioural geneticist from the UFS Department of Genetics), Dr Marieka Gryzenhout (C-rated scientist and Senior Lecturer in the Department of Genetics), and Dr Jaco Wentzel (serves as the pharmaceutical industry partner and consultant for the project at FARMOVS).

In an effort to advance drug discovery and disease research, researchers from the University of the Free State (UFS), the Central University of Technology (CUT), and FARMOVS, a clinical research company associated with the UFS, is developing innovative 3D cell culture models using 3D printed mini bioreactors.

This interdisciplinary project, led by Dr Angélique Lewies, researcher from the Robert WM Frater Cardiovascular Research Centre (Frater Centre) within the UFS Department of Cardiothoracic Surgery, is creating more accurate and human-like models for this purpose, reducing the need for animal testing, and improving the safety and effectiveness of new treatments.

The project was initiated to address the challenges associated with current 3D cell culture techniques, which are often expensive and complex. Recognising the need for a more cost-effective and user-friendly solution, the researchers embarked on this collaboration to develop a novel 3D cell culture system. By making these advanced techniques more accessible, the team aims to enhance the reliability of drug testing and significantly reduce the reliance on animal experiments. This innovative approach not only promises to cut costs but also promotes ethical research practices in the scientific community.

Dr Lewies, whose research specialises in cardio-oncology (relationship between cancer treatment and heart health), particularly in understanding and preventing damage to cardiac cells caused by chemotherapy, leads the cell biology aspects of the project, focusing on the cultivation of 3D cancer spheroid and organoid cultures.

According to her, the project focuses on creating 3D cell cultures, known as spheroids and organoids, that mimic human tissues more closely. These 3D models can improve the reliability of drug testing and reduce the need for animal experiments, aligning with the 3R principles: Reduction, Replacement, and Refinement.

Creating a versatile platform

“Traditional drug discovery and disease studies often rely on flat (2D) cell cultures and animal models. While animal models are essential for understanding disease and testing drug safety, they don't always predict how humans will respond, and their use raises ethical concerns.

“We aim to develop affordable and efficient 3D-printed mini bioreactors for growing these advanced cell cultures. These bioreactors will be designed to fit into existing cell culture labs, making them accessible to researchers. By leveraging the cutting-edge 3D printing technology at CUT's Centre for Rapid Prototyping and Manufacturing (CRPM), the team hopes to create a versatile platform for various research applications,” says Dr Lewies.

She is joined in this project by UFS colleagues; Zurika Murray, a behavioural geneticist, and her colleague from the Department of Genetics, Dr Marieka Gryzenhout, a C-rated scientist and Senior Lecturer. Dr Jaco Wentzel from FARMOVS. is also involved in the project. Dr Wentzel serves as the pharmaceutical industry partner and consultant for the project. With experience in cellular biology and pharmaceuticals, he ensures that the new 3D cell culture models meet industry standards and can be effectively used in drug development. Dr Wentzel’s role is crucial in bridging the gap between academic research and practical application in the pharmaceutical industry.

Goals

According to Dr Lewies, this project aims to create more accurate and ethical models for drug testing and improving the development of new treatments. By combining expertise from engineering, biology, and mycology, the team is set to revolutionise how diseases are studied, and medicines developed. Funded by the CUT and UFS Joint Research Programme, this initiative promises to foster innovation and lead to new research collaborations.

“Cardiac cell damage, known as cardiotoxicity, can lead to serious cardiovascular diseases and is a major reason why some drugs are removed from the market. By developing 3D cancer spheroids and cardiac organoids (mini heart models), my team aims to find ways to prevent this cardiotoxicity while enhancing the effectiveness of chemotherapy drugs.

“Additionally, they are exploring the cardiotoxic effects of natural products, such as medicinal plants and mushrooms, which show potential for both anticancer and cardio-protective properties,” says Dr Lewies.

Experts

Murray is interested in how the psychedelic compounds psilocybin and psilocin affect the brain with her research focusing on the epigenome of genes within the serotonin pathway, which could explain the therapeutic potential of these compounds. “As part of this project, Murray will work with the Frater Centre to develop neuronal organoids (mini brain models) using the 3D mini-bioreactor platform.

“This will allow her to investigate the effects of psilocybin and psilocin on brain function, which have shown promise in treating mental health disorders like depression and anxiety, aiming to understand how these substances might help treat mental health issues,” says Dr Lewies.

Dr Gryzenhout brings her expertise in mycology and is responsible for cultivating medicinal mushrooms used in the project. Dr Gryzenhout's research focuses on the genetic characterisation of medicinal mushrooms and evaluating their therapeutic potential. These mushrooms produce a variety of bioactive compounds with therapeutic benefits, including anticancer activities, heart protection, and immune system support.

Her team is also approved by the South African Health Products Regulatory Authority (SAHPRA) to research the controlled psychedelic compounds psilocybin and psilocin.

Drug Discovery Goals

The project’s long-term focus is on potentially discovering new drugs to prevent and treat heart and brain diseases. Specifically, the team is working on developing therapies for cardio-oncology and neurological applications. In the realm of cardio-oncology, the goal is to find treatments that prevent cardiac cell damage and downstream cardiovascular diseases caused by cancer therapies, while still effectively targeting cancer cells. For neurological applications, the researchers are exploring the potential of drugs derived from medicinal mushrooms, including those with psychedelic properties, to treat conditions like depression, anxiety, and other mental health disorders.

News Archive

New world-class Chemistry facilities at UFS
2011-11-22

 

A world-class research centre was introduced on Friday 18 November 2011 when the new Chemistry building on the Bloemfontein Campus of the University of the Free State (UFS) was officially opened.
The upgrading of the building, which has taken place over a period of five years, is the UFS’s largest single financial investment in a long time. The building itself has been renovated at a cost of R60 million and, together with the new equipment acquired, the total investment exceeds R110 million. The university has provided the major part of this, with valuable contributions from Sasol and the South African Research Foundation (NRF), which each contributed more than R20 million for different facets and projects.
The senior management of Sasol, NECSA (The South African Nuclear Energy Corporation), PETLabs Pharmaceuticals, and visitors from Sweden attended the opening.

Prof. Andreas Roodt, Head of the Department of Chemistry, states the department’s specialist research areas includes X-ray crystallography, electrochemistry, synthesis of new molecules, the development of new methods to determine rare elements, water purification, as well as the measurement of energy and temperatures responsible for phase changes in molecules, the development of agents to detect cancer and other defects in the body, and many more.

“We have top expertise in various fields, with some of the best equipment and currently competing with the best laboratories in the world. We have collaborative agreements with more than twenty national and international chemistry research groups of note.

“Currently we are providing inputs about technical aspects of the acid mine water in Johannesburg and vicinity, as well as the fracking in the Karoo in order to release shale gas.”

New equipment installed during the upgrading action comprises:

  • X-ray diffractometers (R5 million) for crystal research. Crystals with unknown compounds are researched on an X-ray diffractometer, which determines the distances in angstroms (1 angstrom is a ten-billionth of a metre) and corners between atoms, as well as the arrangement of the atoms in the crystal, and the precise composition of the molecules in the crystal.
  • Differential scanning calorimeter (DSC) for thermographic analyses (R4 million). Heat transfer and the accompanying changes, as in volcanoes, and catalytic reactions for new motor petrol are researched. Temperature changes, coupled with the phase switchover of fluid crystals (liquid crystals -watches, TV screens) of solid matter to fluids, are measured.
  • Nuclear-magnetic resonance (NMR: Bruker 600 MHz; R12 million, one of the most advanced systems in Africa). A NMR apparatus is closely linked with the apparatus for magnetic resonance imaging, which is commonly used in hospitals. NMR is also used to determine the structure of unknown compounds, as well as the purity of the sample. Important structural characteristics of molecules can also be identified, which is extremely important if this molecule is to be used as medication, as well as to predict any possible side effects of it.
  • High-performance Computing Centre (HPC, R5 million). The UFS’ HPC consists of approximately 900 computer cores (equal to 900 ordinary personal computers) encapsulated in one compact system handling calculations at a billion-datapoint level It is used to calculate the geometry and spatial arrangements, energy and characteristics of molecules. The bigger the molecule that is worked with, the more powerful the computers must be doing the calculations. Computing chemistry is particularly useful to calculate molecular characteristics in the absence of X-ray crystallographic or other structural information. Some reactions are so quick that the intermediary products cannot be characterised and computing chemistry is of invaluable value in that case.
  • Catalytic and high-pressure equipment (R6 million; some of the most advanced equipment in the world). The pressures reached (in comparison with those in car tyres) are in gases (100 times bigger) and in fluids (1 500 times) in order to study very special reactions. The research is undertaken, some of which are in collaboration with Sasol, to develop new petrol and petrol additives and add value to local chemicals.
  • Reaction speed equipment (Kinetics: R5 million; some of the most advanced equipment in the world). The tempo and reactions can be studied in the ultraviolet, visible and infrared area at millisecond level; if combined with the NMR, up to a microsecond level (one millionth of a second.

Typical reactions are, for example, the human respiratory system, the absorption of agents in the brain, decomposition of nanomaterials and protein, acid and basis polymerisation reactions (shaping of water-bottle plastic) and many more.

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