Clinton Veale in UCT’s native mass spectrometry lab.Credit: Morgan Morris
An organic chemist at the University of Cape Town, has set up what he believes to be the first native mass spectrometry (nMS) facility in Africa.
Native mass spectrometry (nMS) is an evolutionary offshoot of mass spectrometry (MS), a tool designed to identify and calculate the amounts of substances in an analytical sample.
For 10 years, Clinton Veale, an associate professor at UCT, has worked on native mass spectrometry in the pursuit of a way to reduce drug development timeline.
Since the 1980s, mass spectrometry has become especially important in studying proteins. In the early 1990s, nMS began to take shape, building on advances in ‘soft ionisation’ which allowed proteins to be analysed without destroying their delicate non-covalent interactions. These are bonds that allow large molecules to maintain their 3D structure, essential for their biological functions.
This explains some of the differences in the techniques that set nMS apart from traditional mass spectrometry, where molecules are typically denatured using harsh solvents and conditions that lead to a loss of the molecule’s native or original structure.
In native mass spectrometry, the aim is to preserve the molecule as it transitions from the liquid to the gas phase in mass spectrometers. Gentler techniques, using liquid buffers and near-neutral pH levels that mimic the molecule’s original conditions, improve the study of proteins’ interactions with other proteins and the dynamics of molecules assembly.
These advances have opened the door for improved drug discovery1, where understanding how proteins interact and how drugs attach to them, is key.
Some researchers stress that native mass spectrometry should be seen as a complement to other laboratory techniques, not a substitute2. Its advantages include being especially suited to large biomolecules such as proteins, while requiring only tiny amounts of material—measured in picomoles. This makes it valuable in situations where biological samples are scarce.
What stood out for Veale is that in nMS, non-covalent interactions – non-permanent chemical bonds – between proteins remain intact, allowing for more accurate measurement of individual and assembled proteins. In drug discovery, this stability proves especially useful when studying the interactions between different proteins and drugs.
MS is relatively mainstream in South Africa3, but no-one was practicing nMS in South Africa, which means that no instrument was available. While Veale has been using nMS for at least five years and had long been keen to bring the capacity to South Africa, his efforts picked up pace following his move to the University of Cape Town in 2022. He turned to colleagues at his MSc alma mater, the University of Edinburgh, who helped him build the component that adds nMS capacity to an existing MS instrument at his laboratory at UCT.
Financial support came through a Future Leaders – African Independent Research (FLAIR) Fellowship from the Royal Society in the UK, which kickstarted the funding process, and the National Research Foundation (NRF) in South Africa.
A key component of the FLAIR fellowship is skills transfer, explains Veale. For now, he is passing on his own skills to postgraduate students in his department, introducing nMS components into their projects. At the same time, he is working on projects with colleagues at Rhodes University, explaining the value that nMS could add to their research.
David Clarke, chair of mass spectrometry at the University of Edinburgh, and Veale’s nMS mentor, agrees that the technique strengthens Africa’s capacity in the health and drug discovery fields.
“It has the potential to revolutionise the study of health and disease on the continent, as well as unlock novel biotechnological and chemical biology applications,” he says.
The challenge now is to introduce South African researchers to the tool, Veale says. “It’s still a case of getting the South African research landscape to buy into the power of native mass spectrometry.”
Veale is exploring projects with new collaborative partners, and is preparing grant applications for the expansion of current projects to include nMS.
