​Dr Katherine de Villiers from the Department of Chemistry and Polymer Science at Stellenbosch University (SU) is one of only seven scientists worldwide who have been awarded the Simons Foundation’s coveted Pivot Fellowship for 2024.

Founded in 1994, the mission of the Simons Foundation is to advance the frontiers of research in mathematics and the basic sciences. The Pivot Fellowships were established in 2022 to support researchers who have a strong track record of success and achievement in their current field, and a deep interest, curiosity and drive to make contributions to a new discipline.

The Pivot Fellowship will allow De Villiers to join the research laboratory of Prof Iqbal Hamza at the Center for Blood Oxygen Transport and Hemostasis at the University of Maryland School of Medicine for a whole year, starting in July 2024. Hamza’s group specialises in molecular genetics, cell biology and biochemistry in an effort to better understand heme transport and trafficking in eukaryotes, with implications for human health and disease. In 2019, the Hamza lab published a seminal paper in Elife, where they provided unequivocal evidence that knockout mice devoid of a key heme transporter (HRG1) are heme tolerant as a consequence of hemozoin formation. Previously, this crystalline material was only thought to occur in blood-feeding organisms such as Plasmodium falciparum, which do not have heme oxygenase machinery that mammals do.

During the fellowship year, De Villiers hopes to master the necessary lab skills and expertise in cellular biology and genetics to enable her to work at the interface of chemistry and biology. From her side, she will contribute more than 20 years of expertise from the field of bioinorganic chemistry, with a specific focus on understanding the chemistry of heme in the quest to develop the next generation of antimalarial drugs. Heme is an essential iron-containing molecule that plays a vital role in many physiological processes in the cells of all animals and plants. Her research group focuses on understanding how the malaria parasite Plasmodium falciparum manages to sequester toxic heme as hemozoin when it enters red blood cells. This is important because disruption of this process underpins the mechanism of action of numerous clinical antimalarial drugs. She hopes that combining the different disciplines – pure chemistry, biology and genetics – will enable her to contribute meaningfully to dissecting the molecular pathways for the formation of hemozoin in mammals.

De Villiers says she decided to apply for the Pivot Fellowship out of frustration of not being able to answer important questions at the interface of chemistry and biology: “Each time I returned from a Gordon Research Conference on the Chemistry and Biology of Tetrapyrroles, for example, I realised how limiting my background in only pure chemistry was, and how this precluded me from being able to answer important questions”.

At the end of her fellowship, De Villiers wants to bring this multidisciplinary experience back to her research lab at SU: “In order to address the issues that face the modern world, it has become increasingly obvious that multidisciplinary approaches are required. In terms of chemistry and biology, there is often a confluence of the two fields, which has led to graduate programs in chemical biology at many institutions. Here at SU, we developed a chemical biology program at least ten years ago and, more recently, a multidisciplinary program in medicinal chemistry that combines chemistry and physiology.

“With the training in cellular biology and genetics that I will get through this fellowship, I have no doubt that my research group and out outputs will be propelled to a new level. I will be able to legitimately work at the interface of chemistry and biology, and address important research questions,” she concludes.

In the future, De Villiers hopes to continue working with Hamza to also advance the understanding of diseases of excess heme (and therefore iron), such as African iron overload.

Photo credit: Stefan Els