Africa: a new lens on global health 

In 2018, Xolelwa started having debilitating back pain. She was eventually diagnosed with multidrug-resistant tuberculosis.  

Months later, she discovered she was pregnant. Battling severe illness, including the removal of her left lung, Xolelwa gave birth to a healthy baby girl, Lilitha, and began the long road to recovery.  

“It was so hard being away from my baby” she says.

Xolelwa Mabokela and her friends live in Khayelitsha on the edge of Cape Town. Credit: Samantha Reinders.

Xolelwa's friend, Nobuhle, also had TB while pregnant. “TB is still a stigma here and ultimately it is low on the list of people’s priorities. No money, no jobs. People don’t wash their blankets. We have to change our habits.” says Nobuhle.

Xolelwa and Nobuhle's stories highlight the human cost of TB in South Africa, where the disease claimed over 54,000 lives in 2022, one of the highest death rates in the world.

To fight back, researchers need a deeper and more sophisticated understanding of the bacterium responsible, Mycobacterium tuberculosis, and how it interacts with human cells.  

Xolelwa (left) and her friends. Credit: Samantha Reinders.

Sharper views of a silent killer

Around 25km away, at Stellenbosch University, Ben Loos and his team are helping to pilot an ambitious microscopy technique that was developed at the Crick and funded by the Chan Zuckerberg Initiative. It could transform the way diseases like TB are studied.  

Advanced microscopy is often prohibitively expensive and inaccessible to most labs in Africa.  

But through collaboration with the Crick, Ben’s team are pioneering a low-cost, high-resolution technology called Visual Proteomics Correlative Light and Electron Microscopy Kit or VP-CLEM-Kit. As well as testing how to install, run and maintain it in a typical lab, they’re also using the kit to further their research.

Ben Loos and his team in the lab. Credit: Samatha Reinders. 

For Ben and his team, this isn’t just about scientific progress; it’s about impact. By making high-end imaging more accessible, they’re unlocking new opportunities for African researchers to tackle diseases like TB.

Naomi Okugbeni (centre) and Bethaba Shazi (right) are part of the team working on TB research at Stellenbosch University. Credit: Samatha Reinders. 

The VP-CLEM-Kit technology combines two types of microscopy – super-resolution single-molecule localisation light microscopy, which allows scientists to visualise individual molecules inside cells, and volume electron microscopy, which captures the 3D structure of the cell in intricate detail. By superimposing images taken by both techniques from the same cell, it reveals life in unprecedented detail.

“The VP-CLEM-Kit will allow us to make strides in the way we understand many cellular processes,” says Ben. “We’ll get a more detailed view of the structures inside a cell. And that will reveal new mechanisms and treatment avenues for a range of conditions.”

Among the structures studied by Ben’s team are mitochondria, which release energy to power vital processes, including autophagy – essentially the cell’s waste clearance system.  

“It turns out autophagy plays an important role in TB infection,” explains Ben. “For us that was really exciting as we can use the VP-CLEM-Kit to study local strains of TB directly.” 

The team is now infecting living cells with a locally circulating strain of TB to examine the impact on mitochondria, and on the cellular autophagy compartments that are involved in clearing bacteria.  

Nicola Vahrmeijer with part of the new VP-CLEM-Kit. Credit: Samatha Reinders. 

The VP-CLEM-Kit will be able to look at this local strain of TB in incredible detail, and potentially reveal new treatment strategies that help fight the infection more effectively.”  

Imaging innovation

The VP-CLEM-Kit project began over a decade ago, when Ben and the Crick’s Head of Electron Microscopy, Lucy Collinson, were discussing how high-end imaging technologies like super resolution light microscopy and CLEM were often only affordable by well-funded, purpose-built facilities.  

Currently, only one research group in Africa has the capability to perform CLEM.

Ben and Lucy joined forces with physicist Paul French and computational scientists Ricardo Henriques and Amy Strange to create a version that is affordable and easy to use outside of well-resourced facilities.  

Relocating from Ben's lab, Dumisile Lumkwana (left) joined Lucy Collinson (right) to lead the hands-on development of the project. Credit: Michael Bowles.

“The challenge we faced was how to replace an advanced imaging workflow, that requires complex sample preparation and expensive equipment, with something that can be operated more easily and housed in a standard lab or light microscopy facility,” explains Lucy.

Prototype to practice

The new VP-CLEM-Kit arrived in Stellenbosch in September last year. Now the team is taking on a new challenge: turning sample prep, high-powered microscopy and data crunching into one seamless workflow that other African labs could follow in the future.  

Top image: 3D super resolution light microscopy of mitochondria in a cell. Bottom image: CLEM image showing mitochondria (green) inside the cell. Credit: Francis Crick Institute.

As a member of the Crick Africa Network – an equitable programme that aims to increase research capacity to tackle health problems across Africa – Ben is keen to bring innovative technology to the continent.  

“Running standard CLEM experiments requires equipment that is very expensive to buy and run. That is not an option for us, nor for the majority of the labs throughout Africa,” says Ben’s colleague, Nicola Vahrmeijer  

“So this new approach looks at what is available in a standard lab – and how can we achieve unprecedented high-quality 3D imaging using what we already have access to.”

A key issue is sample preparation – “an essential part of the new workflow,” says Nicola.  

One notable change to the VP-CLEM-Kit sample preparation process is that it replaces costly pressurised liquid nitrogen equipment with a much cheaper UV lamp in a standard freezer, making this step far easier and more accessible.  

The bigger picture

Once Ben’s lab has tested and validated the new VP-CLEM-Kit, it will be rolled out to other research institutes across Africa and used on a range of different research projects.  

Another member of Ben's lab, Asandile Mangali, is studying the toxic effects of heavy metals such as manganese, released into the environment during mining. Manganese pollution alters mitochondrial function in ways not fully understood. Credit: Samatha Reinders.

Other team members will use the VP-CLEM-Kit to study neurodegenerative diseases like dementia, by mapping how faulty autophagy and mitochondria contribute to cell ageing and cell stress, leading to diseases like Alzheimer’s.

Meanwhile, Lucy and her collaborators at the Crick continue to refine and automate the technology.

“Working with Ben’s lab has been invaluable for making this technology truly practical,” says Lucy. “We’d love to see the VP-CLEM-Kit in every research institute that needs it, anywhere in the world. Soon, the global south will be the experts, teaching the global north – a refreshing change.”

“It’s an immense privilege and opportunity for us to be part of this work,” says Ben. “With the potential to roll this technology out across the continent, the impact for science in South Africa and beyond is an honour we take rather seriously.  

“We see this as a transformative moment, and the beginning of something much bigger, empowering scientists across the continent to push past what they thought was possible.”  

Back in Khayelitsha, Xolelwa reflects on her TB treatment, “I was really lucky” she said, “there was medication I could take because I was pregnant, and even medication I could change to when I needed to breastfeed my child.”

But TB still claims tens of thousands of lives, and with a crucial need for new diagnostic and treatment strategies, the South African Government has set a goal to eliminate TB as a public health threat by 2030.  

By making high-end microscopy more accessible, VP-CLEM-Kit is unlocking new opportunities for African researchers to help hit that target. 

Credit: Samantha Reinders.